Undocumented migrants in Israel, mostly originating from HIV endemic countries, are not covered by Israel’s universal healthcare coverage. We initiated a Public-Private Partnership (PPP) to handle this public health and humanitarian challenge. The PPP venture included the Ministry of Health (MoH), pharmaceutical companies, pharmacies, and specialized HIV clinics, the Israeli HIV Medical Society , and non-governmental organizations. This study describes the national policy process in conceptualizing and implementing access to HIV services for undocumented migrants through a PPP, and analyzes the preliminary results.This case study describes the process of creating a temporary Public-Private Partnership to provide HIV care for undocumented migrants based on institutional records of the Department of Tuberculosis and AIDS (DTA) and memories and reflections from partners.This case was analyzed according to the OECD-DAC criteria for development assistance . Demographic and serological data of patients referred between 2014 to 2018 were collected to monitor progress. and analyze preliminary medical and biological outcomes. Ethical approval was obtained from the Ministry of Health.Creating a policy to extend HIV care to undocumented migrants was a 15 year process that confronted several challenges within Israeli and international discourse, particularly concerning governmental response to the migration crisis. The use of a PPP model involving numerous stakeholders provided a solid, local feasibility demonstration that extending HIV care as a matter of policy would have positive implications for public health in Israel. During the first 2 years of the program (2014–2015), the MoH funded medical follow-up and the pharmaceutical companies provided antiretroviral treatment (ART) free of charge for only 100 patients at any given time, in addition to ART provided by the MoH for pregnant women. Since 2016, the MoH has fully covered this service and integrated it within the Israeli health system; this constitutes the major success of the PPP program. As of December 2018, the national program has monitored 350 patients and treated 316 (90.3%). The most prevalent disease present upon referral was Tuberculosis.To our knowledge, this study documents the first example of a successful PPP with government partnership in a high-income country to address undocumented migrants’ lack of access to health services in general and HIV care in particular. In light of the intensification of North-South migration, this Israeli case study could be useful for other countries facing similar challenges. It also has lessons within Israel, as the country grapples with other health problems among uninsured communities. Globally, migration remains a controversial topic, and health issues of migrants are often used as a pretext for discrimination . This isIn 2000, the United Nations declared HIV/AIDS (Human immunodeficiency virus/acquired immune deficiency syndrome) ‘a global threat’ . HoweverRecent decades have witnessed vast waves of migration from high HIV endemic/low income countries to low HIV endemic /high income countries, primarily in Europe . In 2015The international response to providing healthcare to non-citizens, particularly the undocumented, varies greatly from country to country. While countries such as Belgium, France, and the United Kingdom extend HIV care to undocumented migrants, many more do not provide any services and even restrict healthcare access . Of 48 rIsrael’s relationship with immigration is complex; since the establishment of the State of Israel, the government has encouraged Jewish immigration, especially in light of anti-Semitism elsewhere . When noIsrael is a country of low HIV/AIDS endemicity, as categorized by the WHO, with a HIV incidence remarkably lower than in most Western European countries , 11. YetAt the end of 2013, there were an estimated 160,000 non-Israeli residents living in Israel without health insurance, equivalent to 2% of the population , 15. AmoSeveral international organizations have emphasized the importance of Public-Private Partnership (PPP) in low-income countries in overcoming challenges to provide affordable healthcare access, particularly in fields of HIV, TB, and Malaria , 19. WhiIn 1997, Israel became one of the first countries to extend Tuberculosis (TB) care to all persons, regardless of citizenship status. This program allowed a full and free of charge diagnosis, prevention and treatment of TB, both ambulatory and hospitalized based, for non-Israeli citizens. While novel at the time, the concept of extending care to non-citizens was based on fundamental human rights and infectious disease prevention and treatment principles . Using tThis case study describes the process of creating a temporary public-private partnership to provide HIV care for undocumented migrants based on institutional records of the DTA and the memories and reflections of partners.p-value of < 0.05 was considered statistically significant.In addition, demographic and serological data (i.e. CD4) of all HIV patients referred to the program were collected for monitoring. The data covered for the period of the creation of the PPP in January 2014 until 2018 - 3 years following its integration into the Israeli health system (in 2016). Continuous variables were analyzed according to the mean, median, standard deviation and range. Categorical variables were analyzed according to frequencies and percentages. Student’s t-test was used to compare continuous variables while the Chi-square test was used to compare categorical variables. A In order to systematically analyze the strengths and weaknesses of our program, the OECD-DAC criteria for evaluating development assistance were used .Ethical approval was obtained from the Ministry of Health.During the period of 1990–2006, only 2766 undocumented migrants from SSA were reported in Israel . NumbersThe DTA next tried to collaborate with pharmaceutical companies, requesting that they provide ART free of charge, while the MoH would fund diagnosis and medical surveillance. Despite months of discussions, this endeavor was unsuccessful at that time.In parallel, the DTA attempted to acquire ART drugs from international suppliers at the cost quoted to low-income countries, but this was rejected due to legal concerns: namely, that pharmaceutical companies that hold the drug patents would file a lawsuit.As a result of these failed attempts, the majority of the undocumented PLWHIV were left untreated, with the exception of urgent care provided upon hospitalization, pregnant women  , and a sBy 2010, 36,616 undocumented migrants from SSA entered Israel . The arrThe DTA mapped the community actors who could potentially serve as partners in this venture, among both migrants and non-government organizations (NGOs). The IATF was commissioned by the DTA to perform an anthropological assessment, including mapping all formal/informal groups within the undocumented migrant population, including individuals with unofficial leadership roles and influence. Some of the HIV positive informants in the anthropological assessment subsequently became community promoters for the program. The DTA also recruited stakeholders from Israeli NGOs, which lead to partnerships with IATF and Physicians for Human Rights Israel.The DTA asked the United Nations High Commissioner for Refugees (UNHCR) to assist in brokering an agreement to allow Israel to purchase ART at a price similar to that in the migrants’ countries of origin. The UNHCR responded that it wasn’t possible, as Israel isn’t financially eligible for subsidized prices. Concurrently, the DTA initiated discussions with senior representatives from the four Israeli Health Maintenance Organizations, and with the managerial staff of each of the 8 pharmaceutical companies which produce/import ART in Israel. Convincing the pharmaceutical company representatives was ultimately successful by holding separate meetings with each company’s representative to address individual company concerns. After the individual meetings, the MoH Director General hosted a meeting with all eight representatives, who are generally in competitive roles, to reach a final agreement. The DTA also organized two national conferences to present the program to relevant professionals and simultaneously mitigate sociopolitical concerns.The PPP partners included the DTA, who led and coordinated the program, the MoH Division of Pharmaceuticals, all regional HIV clinics, a majority of the Tuberculosis clinics, all pharmaceutical companies marketing ART drugs in Israel, one pharmaceutical chain supplier, the Israeli HIV Medical Society, and two NGOs (the IATF and Physicians for Human Rights Israel). Stakeholders met biannually to discuss the progress and obstacles of the program.The first 40 patients accepted by the new program transferred from the IATF program, a majority of who were from SSA and arrived in Israel during the 1990s and early 2000s.New patients were referred to the DTA by HIV clinics, hospitals, and sexually transmitted infections clinics. To be eligible for the program, patients had to have arrived in Israel at least 6 months before referral , have an official form of identification , be ineligible for national insurance, and lack private health insurance.A medical committee composed of HIV/AIDS experts was formed to determine candidates’ inclusion in the program. Patients fell under one of four categories: 1) Approved for medical follow-up and ART; 2) Approved for medical follow-up and put on a waiting list to receive ART; 3) Approved for medical follow-up only and 4) Not accepted into the program. The committee prioritized the patient’s treatment according to ART availability, and determined the course of treatment according to clinical compatibility and medication availability.1Upon acceptance into the program, participants were assigned to one of Israel’s eight HIV clinics where he/she was provided care.ART prescriptions were filled at one pharmacy at the Tel Aviv Central Bus Station. The pharmacy was chosen due to its location at a national transportation hub and proximity to a neighborhood densely-populated by migrants. Patients were only allowed to receive medication in person with proper identifying documents. ART was provided monthly in order to monitor adherence.Pneumocystis carinii and Toxoplasmosis, and all active TB cases were treated [All HIV patients were tested for Latent TB Infection, received a prophylactic treatment for  treated , 25.Following a DTA-funded anthropological assessment of key informants in the undocumented community, a health education program was jointly created and implemented by IATF. This project was implemented by community health workers, and included health education gatherings and distribution of condoms and pamphlets in areas where undocumented migrants live. This was a means both to inform undocumented migrants about the new program and engage the population.The major success of this PPP was its full adoption by the MoH and integration into the Israeli health system at its conclusion in 2016.The national program was largely based on the original joint venture, with three major improvements: 1) the MoH assumed all financial costs of the program including purchase of the ART medications; 2) the budget was significantly increased which allowed more patients into the program and obliterated waiting lists; 3) Patients in the program received the ART in pharmacies operated by the hospitals in which the HIV clinics were located .Table Table During the first period of implementation, the pharmaceutical companies donated ART for only 100 patients at a time. As a result, there was a waiting list, which shrank progressively as the PPP expanded into a national governmental program. Since 2017, there hasn’t been a waiting list for ART in the program.In order to systematically analyze the strengths and weaknesses of our program and allow for global comparison with other health development projects, the OECD-DAC criteria for evaluating development assistance were used . This frThe OECD-DAC defines relevance as “the extent to which the aid activity is suited to the priorities and policies of the target group, recipient, and donor.” Using this definition, the program was found relevant for both undocumented migrants and the partners of the PPP. Considering many undocumented migrants who were referred to the program had extremely low CD4 levels Table , HIV carEffectiveness is defined as the extent to which an aid project attains its objectives. The PPP was very effective in its objective to provide HIV care services as an intermediary step towards inclusion of undocumented migrants in the healthcare system. Before the PPP, access to ART among undocumented PLWHIV was inconsistent and very limited in scope. The PPP’s objective was to increase the number of migrants who could access ART through organized professional channels, which was achieved.The parameters for efficiency involve three parts: 1) cost-efficiency 2) timely achievement of objectives and 3) efficiency compared to alternatives. A cost-utility analysis for the program has yet to be performed. However, the achievements of the PPP were achieved within the 2 year period agreed upon by all parties. In light of alternatives that severely limit or eliminate testing and treatment, including the prior system of only occasional provision of ART by NGOs or complete lack of treatment, the PPP and current national program are considered efficient.Sustainability is defined by OECD-DAC as the whether the benefits of an activity are likely to continue after donor funding has been withdrawn. The PPP program was made sustainable by its absorption into the MoH as a government program, where it was not only sustained, but expanded. The PPP allowed the MoH to progressively increase the budget of government program and to ultimately sustain the entire program without the donation of ART by pharmaceutical companies.Impact is defined as the intentional and unintentional changes produced by a development intervention. The PPP allowed a systematic path to HIV care for more undocumented migrants than prior to the program. However, the stakeholders were surprised by the relatively few undocumented PLWHIV who partook in the program compared to estimates of the number of undocumented migrants with HIV. While requiring further study, some of the reasons for the perceived low yield of the program may include poor access to health systems, fear from formal institutions, and continued migration beyond Israel. Considering both issues of HIV epidemiology and sociological aspects of migrant communities, the low yield did not lessen the impact of the program, which gives institutional footing to providing health services to undocumented migrants in Israel. However, this point requires consideration in building future strategies to maximize the impact in undocumented communities. In addition to more undocumented migrants accessing HIV care, the professional events surrounding the program created a framework for the importance of including undocumented migrants in care. Ultimately, the measure of impact in the HIV field is the UNAIDS 90–90-90 Care Cascade, which recommends that 90% of PLWHIV know they are HIV positive, 90% of those who know they are HIV positive are receiving ART, and 90% of those are virally-suppressed in each country . In ordeIn Israel, the MoH and other stakeholders recognized the public health imperative to treat PLWHIV regardless of citizenship status. Raising the importance of the health issues in the undocumented migrant community and their socio-political ramifications was a process that took several years, numerous meetings, and multiple national conferences. The role of the government in the PPP and its transition to a government program addressed Israel’s human rights responsibilities .The multi-sector partnership unified the abilities and talents of each stakeholder. The partnership with pharmaceutical companies to provide ART for a predetermined period of time without charge to the government or the recipients was a unique success of this process. In this case, IATF’s unique access and experience with this marginalized population provided the initial patient base of the PPP and an acceptable path to procuring donated medication. Additionally, the partnership with IATF contributed to trust with migrants that they would not be deported for seeking treatment.The use of the PPP model was an essential step towards the integration of this service in the Israeli health system. While the issue of extending HIV care required a solution that addressed the financial aspects of providing care, the PPP was a successful means of garnering political support and mitigating potential concerns about the ability of the Israeli system to provide care. As a result of this process, Israel is now one of few high-income countries which provides HIV care, including ART, to undocumented PLWHIV without charge.While the PPP reached a successful conclusion by its transfer to a government program, the capped number of drugs the pharmaceutical companies were willing to contribute to the program limited the amount of people who were immediately accepted for ART. While this limitation was removed after transfer to a government program, limiting patients receiving ART meant composing strict inclusion criteria for the first 2 years.The OECD-DAC criteria were an important tool for analyzing the program. However, further study is needed to quantify several aspects of the program, both in its PPP and government program iterations. Specifically, real-life service accessibility among a politically and economically vulnerable population needs to be assessed, in addition to analysis of serological data to determine changes in transmission and adherence to treatment.Moreover, the DTA estimates a higher number of undocumented migrants living with HIV in Israel than who were referred to the program. Analyzing potential barriers is an important next step. Researchers elsewhere have noted a lack of proof of the effectiveness of government-funded initiatives, mostly due to legal, social, administrative and economic barriers , 29, 30.This article details the process of creating a PPP to manage care for undocumented PLWHIV. To our knowledge, this is the first example of a PPP with state partnership in a high-income country to address an extreme need among the undocumented community. The PPP’s success demonstrated the feasibility of the program, and subsequently resulted in the galvanization of the program into the Israeli health system. While a PPP may not have achieved the same sustainability long-term, its use was an essential interim tool to address ideological and financial hurdles on a practical basis.


Normothermic machine perfusion (NMP) of kidney grafts is a promising new preservation method to improve graft quality and clinical outcome. Routinely, kidneys are washed out of blood remnants and cooled using organ preservation solutions prior to NMP. Here we assessed the effect of cold preflush compared to direct NMP. After 30 min of warm ischemia, porcine kidneys were either preflushed with cold histidine-tryptophan-ketoglutarate solution (PFNMP group) prior to NMP or directly subjected to NMP (DNMP group) using a blood/buffer solution. NMP was performed at a perfusion pressure of 75 mmHg for 6 h. Functional parameters were assessed as well as histopathological and biochemical analyses. Renal function as expressed by creatinine clearance, fractional excretion of sodium and total output of urine was inferior in PFNMP. Urine protein and neutrophil gelatinase-associated lipocalin (NGAL) concentrations as markers for kidney damage were significantly higher in the PFNMP group. Additionally, increased osmotic nephropathy was found after PFNMP. This study demonstrated that cold preflush prior to NMP aggravates ischemia reperfusion injury in comparison to direct NMP of warm ischemia-damaged kidney grafts. With increasing use of NMP systems for kidneys and other organs, further research into graft flushing during retrieval is warranted. Hypothermic machine perfusion (HMP) of the kidney is increasingly employed for preservation of kidney grafts, either additionally after CS2 or as a replacement of CS3. HMP and, to a greater extent, normothermic machine perfusion (NMP) appear to be superior as preservation method when compared to CS5, potentially increasing the donor pool by improving the outcome of transplantation of grafts from extended criteria donors (ECD) as well as from donation after cardiac death (DCD)6. Kidney grafts preserved by NMP sustain less ischemic reperfusion injury after warm ischemia, even when compared to immediately transplanted non-stored kidneys7. Also, graft quality assessment during NMP has recently enabled successful transplantation of declined kidneys9. The optimal perfusion conditions for renal NMP have still to be determined. However, some evidence suggests that normothermic pressure-controlled carbogen-ventilated perfusion is favorable12. The reported perfusion duration appears to be limited in renal NMP, since most studies describe up to 6 h of perfusion time, while only single studies report up to 24 h13, a duration that is already routinely achieved in clinical trials of liver NMP14.In kidney transplantation, the most widely employed method for graft preservation is the use of a cold preflush to remove blood remnants followed by cold storage (CS) at 4 °C, using a preservation solution such as histidine-tryptophan-ketoglutarate (HTK), University of Wisconsin solution (UW), Celsior or others15. The results indicated a trend towards lowered kidney function in the cold flush and storage group, however the NMP time was limited to 145 min.To our knowledge, in recent NMP studies, even in those without a prior CS period, kidneys were preflushed with cold preservation solutions, either separately or during systemic washout of the abdominal organs before organ retrieval. These solutions were designed to provide optimal CS preservation conditions over several hours, not only for flushing. In order to further improve kidney graft quality, the effects of cold preflush should be further examined in the context of NMP. The only study describing direct machine perfusion without cold preflush reported greater ischemia reperfusion injury in kidneys flushed with cold preservation solution followed by CS than in the direct perfusion groupIn this study, we aimed to investigate the isolated effect of cold preflush without subsequent cold storage. We hypothesized that cold preflush before normothermic perfusion (PFNMP) aggravates kidney graft injury in comparison to normothermic perfusion directly after retrieval (DNMP). We aimed to compare the extent of ischemia reperfusion injury between both groups during 6 h of NMP.Guide for the care and use of Laboratory Animals’  and the Directive 2010/63/EU on the protection of animals used for scientific purposes .The experimental protocol was approved by the Institutional Animal Care and Use Committee of the RWTH Aachen University Hospital and performed in accordance with German legislation governing animal studies following the ‘After retrieval and cannulation of both kidneys from the same animal, prior to normothermic perfusion for 6 h, one kidney was preflushed with HTK solution , whereas the other kidney was not preflushed . Perfusate and urine samples were collected, and operational parameters were recorded at eight points in time Fig. . After 6ex vivo perfusion of the kidneys was withdrawn into sterile blood bags filled with 5,000 IU of heparin each . The animals were thereafter euthanized by an IV administration of 1 mL/kg BW pentobarbital . After cardiac arrest, a midline laparotomy was performed and both kidneys were explanted simultaneously to achieve an equal warm ischemic time. The duration from cardiac arrest until explantation was recorded and regarded as warm ischemic time. In compliance with the 3R principle, other organs of the animals were retrieved for different in-house research purposes.Female German Landrace pigs with 55,2 ± 1,9 kg body weight  from a disease-free barrier breeding facility were housed in fully air-conditioned rooms  and allowed to acclimatize to their surroundings for a minimum of seven days and fasted for 12 h before surgery with free access to water. The animals were premedicated with 8 mg/kg BW azaperone , 15 mg/kg BW ketamine  and 10 mg atropine  administrated intramuscularly. After cannulation of the femoral vein, 600 mL of venous blood for the 2O. The kidneys in the DNMP group were cannulated without flushing. Thereafter, in both groups the kidneys were connected to the NMP system and perfusion was started simultaneously at 38 °C for 6 h. In the DNMP group, the first 200 ml of perfusate out of the venous catheter were collected and discarded.After organ explantation, the kidneys were weighed, and the renal artery was cannulated  as well as the renal vein  and ureter  GmbH, Munich, Germany). In the PFNMP group, flushing of the kidney was performed through the renal artery with 200 ml HTK solution  added with 5,000 IU of heparin at 4 °C at a hydrostatic pressure of 100 cmH17 mixed with leucocyte-depleted whole blood was used . From a venous reservoir , the medium was propelled by the pump through the oxygenator into the renal artery and exited the kidney through the renal vein into the reservoir  and oxygenated using a heated (38 °C) oxygenator , ventilated with 1 l/min carbogen . Renal metabolic activity was approximated by calculation of oxygen consumption ((caO2 − cvO2)*RBF/kidney weight) by using arterial and venous oxygen contents, arterial and venous SO2 and pO2 values and hemoglobin concentrations (ca/vO2 = Sa/vO2*1.34*c(Hb) + pa/vO2*0.0031). Urine was collected separately, and the urine output was recorded. The perfusate volume was replenished after measurement with basic Ringer’s solution to compensate for the excreted urine volume. Perfusate plasma samples and urine samples were stored at −80 °C for subsequent analysis. Perfusate samples were analyzed for sodium and creatinine levels. Protein, sodium and creatinine concentration were determined in urine samples. Using arterial perfusate and urine levels, creatinine clearance (urine creatinine*urinary flow/plasma creatinine/kidney weight) and fractional excretion of sodium (urinary sodium*plasma creatinine/plasma sodium/urinary creatinine) were calculated.Samples of arterial and venous perfusate and urine were collected at distinct points in time Fig. . ArteriaTM, BioRadInc., Munich, Germany).Urinary levels of the acute tubular injury marker neutrophil gelatinase-associated lipocalin  were determined at the end of reperfusion using enzyme linked immunosorbent assay (ELISA) according to the manufacturer’s instructions. The absorbance was detected at 450 nm using a microplate reader  and digitally scanned using an EVOS-microscope . The histological images were analyzed according to a tubular injury score , an osmotic nephropathy score  and presence or absence of hypokalemic nephropathy. All analyses of the slides were performed by a senior nephropathologist in a blinded fashion.Statistical analysis was performed using GraphPad Prism 8 software package . After performing a Shapiro-Wilk normality test, two-way analysis of variance (ANOVA) and multiple comparison were used followed by Bonferroni post-test correction for all measurements during perfusion. For kidney weight, hemorrhage and histological analysis, one-way ANOVA was applied. Data are presented as mean ± SEM and a p value < 0.05 was considered statistically significant.The weight of the kidneys was measured before and after reperfusion. Before reperfusion, the weights did not differ significantly between groups  or without preflush (DNMP group) prior to 6 h reperfusion using a normothermic machine perfusion (NMP) system. In comparison to the DNMP group, PFNMP kidneys gained more weight during reperfusion and histological samples showed a larger degree of osmotic nephropathy. Kidney function was impaired in the PFNMP group as indicated by deteriorated glomerular and tubular function, lower metabolic activity, higher lactate levels, higher concentrations of urine protein and a higher release of NGAL in urine. The detrimental effect of cold preflush was pronounced for approximately four hours after which the parameters in both groups converged.9. To our knowledge, in all reported NMP studies, kidneys were subjected to cold preflush. While a previous study reported increased histological injury after cold flush and cold storage followed by NMP15, our findings suggest that cold preflush prior to NMP has detrimental effects on kidney function and preservation quality, when compared to DNMP. Although the approach of direct NMP cannot be easily adapted into clinical practice as it is clinical standard to washout the donor’s vasculature with cold preservation solution before organ retrieval, avoiding or minimizing the detrimental effects should be studied further in the context of NMP. The employed preservation solutions might be optimized for use as flushing solution for NMP, since most preservation solutions were developed for optimal outcome in CS preservation. It has recently been shown that a combination of different solutions for flushing and CS can be superior to the use of a single solution18. Additionally, other approaches, such as warm flushing with a novel phosphate-free preservation solution (AQIX) prior to NMP19 and recently, normothermic regional perfusion as a method to reestablish circulation in DCD donors20, showed beneficial effects on kidney graft function and transplantation outcomes.NMP has been employed as a novel method for kidney preservation, in particular for resuscitation and viability assessment of warm ischemia-damaged grafts21. We used HTK because it is the clinical standard solution for flushing and cold storage preservation of kidneys in Germany and has the largest market share of all preservation solutions worldwide. Moreover, for flushing of DCD kidneys HTK is also a frequently applied preservation solution due to the low viscosity, when compared to University of Wisconsin solution.It has been demonstrated that HTK, UW, Celsior and Euro-Collins have comparable efficacy for flushing and cold storage preservation of kidney graftsIn the experiments, kidneys from young animals with a mean weight of 56 kg were procured and these were flushed out until the effluent was macroscopically free of blood remnants. We found in preliminary experiments that 200 ml of HTK was sufficient. Additionally, this is equal to the amount of perfusate that was discarded in the DNMP group.22. However, it was discussed by the authors that total elimination of the added creatinine was the cause.During our study, after approximately 4 h of reperfusion, the beneficial effect in the DNMP group on functional parameters  returned to comparable levels seen in PFNMP. This might be on the one hand a result of hypokalemic nephropathy and severe hypernatremia, which were more pronounced in the DNMP group. An optimized perfusate composition for DNMP could potentially maintain the improved results in this group during the final two hours of reperfusion. On the other hand, another obvious explanation of the reduction of the beneficial effect of DNMP over time could be the rapid deterioration of kidney function in both groups found after approximately 3 h of NMP as expressed by IRR, creatinine clearance, FENa and urine protein. In contrast to NMP of other solid organs, studies of prolonged renal NMP are rare. A previous study using a similar Ringer’s-based perfusate for NMP of a porcine kidney with only 6.7 min of warm ischemia time reported also a decline in creatinine clearance after 3 h of perfusion time3, an extension of the achievable perfusion time could increase clinical application of NMP. A recent study showed that recirculation of urine could maintain electrolyte levels and achieve 24 h of NMP after CS13. Another group demonstrated 16 h of kidney perfusion time using a perfusion medium containing Steen solution, originally designed for lung NMP containing albumin and dextran3. In both experiments, oncotic pressure was maintained at a normal level by albumin, while our perfusate had an estimated sub-physiological oncotic pressure of 8.5 mmHg. In both groups of our study, a weight gain took place during perfusion, indicating edema and a potential contribution to the decline in kidney function over time. Unfortunately, the mentioned studies did not report kidney weights and gains. Additionally, another group reported that the use of leucocyte- and platelet-depleted blood in NMP results in improvement of renal function parameters23, indicating that an additional depletion of platelets might be beneficial. Aiming to extend achievable perfusion times and reduce graft injury, more research on optimal perfusion preparation methods and perfusion conditions is warranted, including systematic approaches to improvement of perfusion media since there are no comparative studies reported to date.Since continuous NMP has been shown to be superior to NMP combined with CSIt could be argued that direct NMP was not applied, but rather a warm flush with perfusate which was thereafter discarded. However, cooling down of the kidney by cold flushing was avoided and the initial perfusion medium was discarded to eliminate accumulated hypoxia-induced and inflammatory mediators. In our study, for ethical reasons, kidneys were obtained from animals employed in other experiments. The kidneys, however, were procured after a comparable period of warm ischemia and before other procedures were performed on the animals.in vivo transplantation studies are necessary.The duration of NMP was limited to 6 h and the objective was to investigate the isolated effect of the cold preflush on organ grafts without influence from other organs. To assess, whether the observed detrimental short-term effects of cold flush lead to significant long-term effects and clinical outcomes such as primary non-function, delayed graft function and reduced graft survival, longer durations of NMP as well as a model using reperfusion with whole blood and eventually 24, suggesting that rewarming plays an important role, as evidenced also by the current study.From this study, the mechanism of aggravated ischemia reperfusion injury in the PFNMP group remains unclear. The observed effect could be the result of the cold flush or subsequent rapid rewarming in the NMP system. A recent study compared cold-stored kidney grafts subjected to NMP with or without a controlled oxygenated rewarming (COR) procedure and found improvement of kidney function after CORTo conclude, the detrimental effect of cold flush prior to NMP was demonstrated when compared to direct NMP. Kidney function was impaired for the first 4 h of reperfusion and renal tissue damage at histological level was increased. Improved procedures for kidney preparation before NMP could potentially improve preservation quality and clinical outcomes. Moreover, further improvements to NMP are required to achieve prolonged perfusion durations necessary for routine clinical application of NMP for kidney grafts.


Cancer centers are beginning to emerge in low- and middle-income countries despite having relatively few oncologists and specialists in related fields. Uganda, like many countries in sub-Saharan Africa, has a cadre of highly motivated clinician-scientists-in-training who are committed to developing the capacity for cancer care and research. However, potential local mentors for these trainees are burdened with uniquely high demands on their time for clinical care, teaching, institutional development, advocacy, and research. Facilitated peer mentoring helps to fill skills and confidence gaps and teaches mentoring skills so that trainees can learn to support one another and regularly access a more senior facilitator/role model. With an added consultant component, programs can engage limited senior faculty time to address specific training needs and to introduce junior investigators to advisors and even potential dyadic mentors. Two years after its inception, our facilitated peer mentoring career development program at the Uganda Cancer Institute in Kampala is successfully developing a new generation of researchers who, in turn, are now providing role models and mentors from within their group. This program provides a practical model for building the next generation of clinical scientists in developing countries. Eleven trainees completed a 13-month fellowship in Seattle that included didactic training in epidemiology, statistics, and the responsible conduct of research along with clinical rotations at the Seattle Cancer Care Alliance. These trainees have subsequently developed research projects toward a degree in programs at Makerere University or the University of Washington.The Uganda Cancer Institute (UCI)/Hutchinson Center Cancer Alliance (Alliance) was established in 2008 between the UCI and the Fred Hutchinson Cancer Research Center in Seattle, WA, to build capacity for collaborative clinical research on the pathogenesis, epidemiology, detection, and treatment of cancers, especially those related to infectious agents.4 However, geopolitical and cultural changes late in the past century left Uganda with a relatively small population of mid- and late-career medical scientists available for this type of mentoring commitment.5 According to in-country surveys, senior scientists and faculty members have insufficient time or training to meet the mentoring needs of the growing number of students and postgraduate trainees who attend programs of Makerere University’s College of Health Sciences, one of the premier medical schools in East Africa.7 Past and present deans and several faculty members of the four schools within the College of Health Sciences  have served in advisory roles for the funded programs that benefit the Alliance’s Ugandan trainees. However, in Kampala, the Alliance itself has only one senior faculty member whose responsibilities include the directorship of the UCI (J.O.) and one junior faculty member from Seattle who lives in Uganda (W.P.). Research mentoring of Alliance trainees by Seattle-based senior scientists affiliated with the Alliance has been limited by 10- to 11-hour time zone differences, the intermittent availability and quality of communication technology, and infrequent formal and informal face-to-face encounters.Continued career development of trainees in academic medicine traditionally is aided by dyadic mentoring—the ongoing collaborative interaction between the trainee and a more-experienced committed clinical scientist.12 In 2011, Herbert et al13 described an especially appealing consultancy model in which peer mentees from an interdisciplinary program in geriatric medical research select and engage senior consultants to provide in-depth and guided responses to challenges posed by the group. This approach leverages the time of senior faculty and provides leadership opportunities for peer mentees.13 To support the mentorship and career development of Alliance trainees and their colleagues in Kampala, we created a peer mentoring consultant program on the basis of these models. We describe the peer-driven evolution of the core consultant program into a multifactorial, peer mentoring career development (PMCD) program , but by 2013, as many as 20% of weekly sessions were facilitated by one of several Alliance peer mentees. To maintain a safe and relatively intimate environment, the RIP meetings generally were not broadcast remotely, but trainees or faculty occasionally joined sessions through Skype  or WebEx  if requested.In response to the needs of Alliance scientists-in-training, a weekly research in progress (RIP) meeting was started in 2010. Regular attendees (peer mentees) include Alliance trainees and research personnel as well as UCI medical officers, nursing officers, and pharmacists.In 2013, a confidential survey was administered to 38 individuals who were regular attendees of RIP meetings. Of the 38 individuals surveyed, 24 (63%) stated that they were currently involved in research, 25 (66%) had attended most of the RIP sessions to date, and 36 (100% of 36 responders) agreed that RIP meetings are a good use of their time. Furthermore, 35 of 36 (97%) who responded agreed that they would like to have more mentoring and career development topics included in the RIP meetings.The survey also revealed that only half of responders (19 of 38 [50%]) believed they had opportunities to develop leadership skills at work. Only eight of 38 (22%) expressed they were satisfied with their progress in finding a mentor, and just three of 38 (7%) believed that they had many opportunities for networking with other researchers.To address the apparent gaps in mentoring, leadership development, networking, and skills mastery, we (W.P. and R.A.M.) conducted a 2-hour workshop in Kampala in 2013 with 17 peer mentees to identify group values, agree to basic goals, and create a list of career development topics or concerns that the mentees hoped could be addressed by senior consultants. We brainstormed in small groups of two or three attendees and compiled the group suggestions to assure that all peer mentees were represented. The groups unanimously reported teamwork as a top value and set goals that included continuing weekly RIP meetings, starting a consultant program for skills building, and using the consultant program to increase networking opportunities .Workshop attendees identified 31 topics for possible future consultant presentations; topics included research design and implementation, career management, and professional skills training . One of 15In the first 2 years of the program, the peer mentee group held nine didactic consultant sessions, eight skills workshops, and one town hall meeting. Of these 18 sessions, nine (50%) involved local Ugandan consultants, and the remainder were led by faculty from Seattle. In general, a peer mentee volunteers to contact the consultant before the session to discuss the questions the group hopes to have addressed. The peer mentee also facilitates the session. Consultants often use slides for their talks but are encouraged to interact with the peer mentees and to elicit discussion. Slides or supplementary materials are posted, with permission, to an open-access Web page maintained by the Fred Hutchinson Cancer Research Center’s Arnold Library in Seattle.Attendance for the 15 open sessions ranged from 23 to 70 , whereas attendance for three closed sessions ranged from seven for each of two manuscript writing workshops to 23 for a workshop on how to interpret statistics in scientific manuscripts. With permission of the consultant, evaluations are elicited at the end of each session (Data Supplement). Nearly all respondents  ranked the sessions as very useful—the highest rating. Responses to the question, “What will you do differently as a result of having attended this session?” often revealed that attendees planned to incorporate new skills or practices described by the consultant. Overall, satisfaction with the sessions was high, with comments such as “make them more frequent” and “it’s fantastic” in response to the question about how the consultant sessions could work better.Within the first year of the program, peer mentees had received a substantial amount of training in literature search and scientific reading skills. One of the peer mentees, an Alliance medical officer with ongoing research interests, independently started the Journal Club by using one of the regular RIP sessions for the time and venue. The program provided questions that were based, in part, on course materials from the first consultant session (How to Read the Scientific Literature). The peer mentee uses these questions to guide the critical evaluation of the study design, the quality of the statistical approach and data presentation, and the validity of the conclusions stated in the selected article. Since mid-2014, when Journal Club began, the group has maintained a monthly schedule, with peer mentees selecting an article of interest and a discussant for each session.Evaluations are not elicited after Journal Club sessions; however, we did ask about the Journal Club in surveys administered to the overall peer mentoring group at the end of 2015, when the club had been active for 18 months. Most respondents (45 of 57 [79%]) indicated that they had attended Journal Club, with more than half (25 of 43 [58%]) reporting that they had attended three or more monthly meetings. The majority of Journal Club attendees (36 of 44 [82%]) believed that the club helped them to read the scientific literature more skillfully; 82% (36 of 44) believed that the club affects their clinical practice or research thinking, and 89% (40 of 45) agreed that the club was a good use of time.Midway through year 1, in response to peer mentee requests and with additional funding, we launched a workshop series to increase understanding of ethical research and clinical practice. Biomedical research integrity (BRI) workshops take place once a quarter and use a case-based, small group format in which attendees practice bioethical decision making. The facilitator leads a group discussion on the basis of prepared concepts or guidelines for each case. In the first 2 years of the PMCD program, the BRI sessions covered six topics, including human participants and medical ethics, ethical authorship, ethical mentorship, laboratory practice, and data integrity. In contrast to Journal Club, Seattle-based Alliance faculty members write the cases for presentation and facilitate these workshops. An evaluation form is distributed after each session to probe the acceptability of the format, usefulness of the topic, and to elicit desired topics or changes to the BRI sessions. Of 58 peer mentees surveyed in 2015, 33 (57%) had attended one or both of the two most recent BRI sessions. Of these attendees, 32 (97%) believed that these workshops were a good use of their time.t test and χ2 test were used to analyze selected outcomes measures. Results of the 2014 survey have been reported.16 Here, we report the results of the 2015 survey taken 2 years after beginning the consultant component of the PMCD program. Journal Club had been in place for 18 months, and the BRI workshops had been offered for 10 months.As the PMCD program evolved, we attempted to measure its effectiveness through surveys after each consultant or BRI session and by comparing responses to scaled surveys conducted at the beginning of the consultant program (baseline) in 2013 and at 1 and 2 years later. Thirty-eight members of the peer mentee group responded to the baseline survey; 43 responded to the 1-year survey, and 58 responded to the 2-year survey in 2015. The increased number of respondents over time reflects growing involvement in the program, which could be partly due to the increase in the number of UCI medical personnel and Alliance trainees, the opening of a new Alliance building with a larger training venue, and/or increased awareness of the PMCD program. The confidential surveys contained several questions  to determine attendance history and satisfaction levels with components of the program. Questions with scaled answers were included to measure confidence, leadership, mentoring, and career development. Answers to each survey were entered into SurveyMonkey . Student’s In the 2013 baseline survey, 63% (24 of 38) indicated they were involved in research, as did 78% (32 of 41) in 2014 and 65% (37 of 57) in 2015. The post-2-year survey in 2015 revealed that 18 of 55 (33%) respondents had attended RIP meetings for 1 to 3 months, 14 (25%) for 4 to 6 months; eight (15%) for 6 to 12 months, and 15 (27%) for > 12 months. As we found in the baseline survey, RIP meetings were considered a good use of time in the post-2-year survey (51 of 55 [93%]), with four of 55  stating they were unsure.Of the 19 scaled questions in the 2013 survey, a number were repeated in subsequent surveys. v 3.06; P = .005), perhaps reflecting skills gained through Journal Club as well as consultant sessions in the professional skills training and scientific writing skills categories  scored significantly higher than new attendees, especially in areas covered specifically by didactic or workshop sessions, such as research skills and mentoring. For instance, veterans agreed more strongly than new attendees with the statement “I feel confident in critically reading and interpreting scientific papers”  and reflected much higher agreement than new attendees with the statement “I have developed the ability to lead a team” .Overall, the PMCD program seems to have influenced a sense of leadership ability in veterans. Veterans reported higher agreement than new attendees with the statement “The program has helped develop my leadership skills”  and “I feel able to manage the frustrations of conducting research” .The measures of sense of community and confidence in science, although relatively high at baseline and in new attendees, were highest in veterans of the program. For example, veterans more strongly agreed than new attendees with the statements “I do not feel alone in facing the challenges of research science” . Research mentors were more likely to have attended most (> 50%) of the RIP sessions in the previous year (six of 11 [55%] v 11 of 32 [39%]) and to have attended Journal Club more than four times in the previous year (six of 10 [60%] v 12 of 23 [38%] of those attending).The ultimate goal of a PMCD program like ours is to graduate peers to roles of mentorship within their own independent research or clinical endeavors. In the 2015 survey, we sought to determine a baseline of mentoring activity within the group so that we could determine in later surveys whether mentees were indeed converting to greater mentoring roles. A substantial proportion of respondents reported that they often mentored others for clinical issues or practice (29 of 43 [62%]), for career development (12 of 43 [27%]), or for research-related issues (11 of 43 [26%]). Because our Alliance emphasizes growth and independence in research, we were particularly interested in learning more about those who were often research mentors. Not surprisingly, those who often mentored for research issues were more likely than nonmentors in research to have been in the program for > 12 months . They also had a greater sense of community by several measures and were more strongly in agreement that they had gained confidence by attending PMCD meetings . The most striking difference was in leadership development. Research mentors believed more strongly than nonmentors that they had developed the ability to lead a team  and responded with higher scores to the statement that the program had helped to develop their leadership skills . In summary, those individuals who were more experienced and active in the PMCD program were more likely to start mentoring others.We compared weighted responses from the 11 research mentors with the 32 who sometimes (17 of 43 [39%]), rarely (seven or 43 [16%]), or never (eight of 43 [19%]) mentored for research-related issues (nonmentors). These two groups had similar scores for confidence in their communication skills, research ability, and research knowledge. The groups had similar scores for topics related to having ideas for finding mentors and for their level of satisfaction in finding their own mentors . HoweverThe assessment of the direct effect of our program on research output at this early stage is challenging. Still, participants in the PMCD program have many important accomplishments to suggest that the program is supporting the successful development of junior investigators. In the first 2 years of the program, peer mentees participated as study nurses, study doctors, or as investigators in > 25 research studies conducted at UCI. Trainees presented 15 abstracts at international conferences on the basis of their work during this time. Several PMCD participants also enrolled in higher degree programs, including two who completed master in public health degrees and five who are currently pursuing doctorate in philosophy degrees. Five peer mentees successfully obtained independent grant funding in the first 2 years of the program, including two Beginning Investigator Grant for Catalytic Research awards from the National Cancer Institute. Furthermore, seven peer-reviewed articles were published by program participants by the second year of the program, and several more have been published since. In addition to focusing on research skills development, the PMCD program emphasizes leadership development. In the 2 years after the period of this study, peer mentees have assumed several leadership positions within the UCI, including director of clinical services, director of community outreach, director of satellite clinical services, founding secretary of the UCI institutional review board, and head of the UCI research and training directorate. One peer mentee has also assumed the directorship of the clinical microbiology laboratory at Makerere University.For those who are considering starting a peer mentoring program, we would advise that the following elements be incorporated. First is a core identity or underlying common purpose as identified by the group itself. For new cancer centers in low- and middle-income countries, peer groups might easily arise from the common challenges faced by clinicians new to oncology or by a group of early-stage scientists who are undertaking cancer-related research projects. Participation in the program should be voluntary to ensure that group members have an interest in research and skills development. 9 Protected support staff time, which required approximately 0.25 to 0.5 full-time equivalents for our program, is helpful for supporting program communications, tracking, and evaluation. The second element is staff time for logistics and communication. Having ongoing assistance to track attendance, register attendees for consultant sessions, send meeting reminders, and administer evaluations is invaluable. Small groups may be able to rotate these duties, but even routine functions can become burdensome to busy trainees or junior faculty.17 Ideally, this advisor would reside in the country to attend program activities and provide regular face-to-face interactions with the group. The third element is having a senior facilitator or advisor—a key element for new groups to help to establish goals, to be a role model and advocate, and to provide counsel to keep the group going in the early stages.The fourth element is to augment, but not manage, existing or nascent mentoring dyads. Some trainees had existing mentoring relationships, particularly those enrolled in formal degree programs, whereas others did not. Our PMCD program was not designed to assign mentors to trainees but, instead, to provide guidance on how to identify a mentor and how to manage the mentor-mentee relationship. Each individual peer mentee was responsible for managing exchanges with mentors outside the group. 18 may thrive within relaxed programmatic parameters that depend more on relationship and trust building than on rules. Our PMCD program allows individuals to participate as much or as little as their schedules and interests allow. Most peers express pride in the PMCD program and engage in regular reviews to revise goals, identify needs, and brainstorm changes they want to implement. The fifth element is to empower peer mentees. Trainees in countries with a relatively collective rather than individualistic viewpoint of group interactionThe final element is to encourage organic transformation. Peer mentee empowerment leads, naturally, to programmatic changes. Alliance faculty members support such changes, a factor that may encourage peer mentee engagement.7 to mentor junior scientists with their research projects within the Alliance.The PMCD program emanated from a weekly facilitated meeting of peers who had a common interest in cancer care and cancer-related research. The program has evolved quickly, but organically, to encompass four separate but interrelated training and leadership modalities . The pro10 The conceptual framework and motivation of our PMCD program draws heavily from the rationale by Pololi et al,17 who emphasized the importance of applying adult learning precepts to what they termed collaborative mentoring. In collaborative mentoring, a supportive learning environment is coupled with learner engagement. This approach follows Rogerian principles of adult learning in which a safe, nonjudgmental learning environment is stressed and learning occurs through experiential opportunities.19 The RIP meetings create a supportive setting, whereas the consultant program emphasizes group empowerment by having the peer mentees identify their group’s values, develop their own learning and program goals, and take responsibility for implementing the program.Peer mentoring within groups of junior faculty arose in response to the lack of senior faculty availability for classic dyadic mentoring.4 Potential disadvantages include the development of professional or personal rivalries within the group as individuals strive toward recognition and promotion. To this point, our group seems distinct from those described in North American academic medical systems.9 A values exercise held during the planning meeting for the consultant program revealed that teamwork and kindness/charity were the two most frequently stated values. These values have been reflected in mutual peer respect and overall commitment to the group’s success. As a result, we have not encountered difficulties with intragroup competition as individuals develop in their careers.4 A second potential limitation of peer mentoring is the inherent lack of experience of the mentees with their related inability to provide networking to their junior scientist–level peers. The consultant system was designed specifically to expose peer mentees to a variety of vetted, senior faculty members and to provide introduction points to potential dyadic mentorship opportunities. To encourage networking, the program has had an open-door policy with widely advertised consultant sessions for all but three of the 18 didactic presentations or skills workshops in its first 2 years.Peer mentoring has the advantage of reducing the power differential inherent in dyadic mentoring relationships.21 and as interpreted for careers in academic medicine,22 is especially well suited for resource-challenged institutions where organized, dyadic mentoring programs may not be feasible. Along with self-management of a trainee’s career track, as facilitators , we emphasize the importance of seeking multiple situational mentors for focused advice. Each local expert who has served as consultant has invited attendees to follow up with them for more-specific advice. Anecdotally, these invitations have been accepted in a number of cases. Limited studies indicate that mentoring dyads that connect organically can become both long lasting and meaningful.17The structure, content, evaluation process, and support mechanisms of our PMCD program place responsibility for career development largely on the individual trainee. This concept, derived from business preceptsComparison of baseline and post-2-year survey data suggests that veteran (> 12 month) program participants show increased confidence and heightened perceived ability to find mentors. Furthermore, veterans have significantly higher scores than program newcomers for leadership measures and for a sense of community. Perhaps most tellingly, a substantial number of veteran peer mentees have assumed roles as mentors for others in research endeavors.Our survey techniques had a number of limitations. Because they were designed to provide feedback that would be useful to build the program, we did not track who took either survey and, therefore, could not make direct assessments of how the program influenced individual participants. Furthermore, because we wished to have anonymous responses, we avoided having respondents identify their occupations or the depth of their involvement with research. Although this method allowed for frank comments , biases may have been introduced by regularly attending group members whose professional needs are not the focus of the program. For example, several regular attendees are highly experienced and professionally confident senior nurses who have limited interest in specific aspects of research skills training. Our use of veteran or long-term attendees would also select for those who found the program useful enough to continue participation. Conversely, some of those who responded to either survey may have had only passing exposure to the program. Finally, we had no way to determine who may have been missed in the surveys. In particular, we did not attempt to track those who had attended and then accepted a graduate or professional position outside Kampala. Their input about the effect of the program on their careers, although potentially valuable, was not sought. The identification of dropouts and their reasons for departure would be of interest.The initial goals of the PMCD program have been met and, in many ways, exceeded as a result of peer interest, engagement, and growing peer leadership. Peer group members are taking increasing responsibility for PMCD components as they advance in research and clinical experience, confidence, and leadership. As peer mentees advance to roles as mentors, PMCD facilitators, and consultant session leaders, we anticipate additional organic changes. Meanwhile, the basic precepts and simple organization scheme of our PMCD program may provide a roadmap for other cancer research programs to create similar effective peer mentoring groups for career development of junior faculty and research trainees.


The ACGME has the monumental task of guiding educational standards that are designed to both protect the public welfare and further educational programs. Many educational standards are objective, such as quantitative performance on examinations, involvement in research, and involvement in systems development and quality improvement. However, key clinical performance measures are based on prior training and experience. Over the last several years, studies examining rates of abuse and discrimination during post-graduate medical training in both the United States and Canadian studies, which have reported alarmingly high rates of 50%. With the increasing utility and availability of social media, such issues have become more transparent to the public. A plethora of studies has been conducted, examining physician biases towards patients, practice changes, insurance company regulations, and evolving healthcare systems. However, a significant amount of evaluation is merited when examining individual institutional cultures and the educational environments that harbor them. We wish to examine the role of ever-evolving specialty-specific ACGME-instituted educational milestones in Internal Medicine and Opthalmology in the context of potential cognitive biases and their implementation within post-graduate training programs.The course of study for young physicians for post-graduate training is an exciting and life-changing opportunity, one that is filled with the relentless optimism of intellectual discovery and personal growth and development. The American Council for Graduate Medical Education (ACGME) is a non-profit private council that evaluates and accredits internship, residency, and fellowship programs. The role of the ACGME is to oversee curriculums, training environments, and specialty evaluation standards to ensure satisfactory competency leading to board eligibility and certification in the respected field of study. With the objective of examining the role of cognitive bias in the context of the American Council for Graduate Medical Education (ACGME)-defined specialty-specific educational milestones, a clinical definition must first be examined. The concept of cognitive bias is defined as the manner by which human beings process information and develop a hypothesis, particularly when assessing complex tasks at various stages of development. The concept of cognitive bias in educational assessments in post-graduate training programs is multi-faceted . Based oThe halo effect in cognitive psychiatry is defined as an individual having a desirable trait that affects perceptions more universally and broadly . The defConversely, the concept of the reverse halo effect, also known as the devil effect, may unfairly impact the evaluation of a resident or fellow by faculty. An undesirable trait in a trainee may become representative of most, if not all, milestone competencies being assessed. Based on geographic, cultural, and institutional norms, the definition of an "undesirable" trait can be variable. It's not uncommon for faculty to sublimate personal biases that create a focal point in what determines an undesirable trait. In the context of a training program where a program director has a disproportionate amount of power, this form of bias may potentially have catastrophic consequences on a young physician’s career, reputation, and livelihood. The ACGME has made strides in promoting against institutional nepotism. In comparison to early career and financially limited trainees, large hospital systems have significant legal and financial resources with which to assert their will and public image to the Centers for Medicare and Medicaid Service (CMS) and accreditation bodies such as the Joint Commission. In the hierarchy of a hospital system, a program director and section chief are much more likely to support their own faculty rather than a trainee, even with little direct evidence .The reverse halo effect could also be acquired when a member in a department wishes to raise their own stature by tacitly disparaging another member of the department. Frequent assassinations of trainees' reputations within a program may lead to the development of a scapegoat culture, especially as such programs are likely to foster a herd mentality. The change in perception does not occur immediately and could develop over months or even a year. The result of such biases are feelings of inadequacy, stress, and depression in previously motivated and dedicated trainees . ProgramACGME program requirements are broad and encompass a vast variety of competencies on both house-staff and faculty. A core requirement, for example, is that "the faculty must evaluate fellow performance in a timely manner during each rotation or similar educational assignment and document this evaluation at the completion of the assignment." To illustrate, if a faculty member has a personality conflict with a trainee, the motivation for completing an evaluation in real-time markedly diminishes. In doing so, the educational and personal growth utility of performance evaluations decreases -5. AdherACGME milestones projectThe Milestones Working Groups for all accredited specialties and subspecialties were initially established by a joint venture with the Accreditation Council for Graduate Medical Education (ACGME), the American ‘Board of Internal Medicine (ABIM), and the Alliance for Academic Internal Medicine (AAIM) and involved both community physicians and academicians. Individually, tailored specialty-specific milestones were constructed into several dozen metrics that each required satisfactory ratings for trainees for promotional decisions and the establishment of board eligibility. At the completion of each monthly rotation, an online assessment through GME-approved software is completed with specific ratings, each of which is tethered to a core competency. These competencies are with respect to professionalism, medical knowledge, problem-based learning, procedural skills, and interpersonal skills. Typically, each educational goal is assessed on a scoring scale from one to nine, with a five or higher being defined as a satisfactory rating. The milestones within individual specialties are evaluated throughout the course of a trainee's education to identify individual educational trajectories and deficiencies, the goal being to achieve a "ready for unsupervised practice" status on individual milestones. Each component of the evaluation process has an inherent propensity for cognitive bias from a program and faculty perspective. We wish to examine the correlations in cognitive bias with official ACGME-defined educational milestones in further detail.Within surgical specialties such as Ophthalmology, the 360-degree longitudinal milestones include both surgical and non-surgical evaluations. Within medical specialties, such as Internal Medicine, a broader evaluation is evident, which includes the synthesis of complex tasks and preparation for serving as both a generalist and a consultant. The scope of practice, as defined with the ACGME and the American Board of Ophthalmology (ABO), for example, requires trainees to achieve competency in the management of common toxicities associated with the treatment of central nervous system (CNS) lymphoma, endophthalmitis, retinal detachment and common identifications of optic neuropathy . With thEvaluation of cognitive bias in ACGME milestones To illustrate the role of cognitive bias in post-graduate training, in-depth comprehension of metrics being evaluated must be established. The ACGME publishes specialty and subspeciality-specific metrics and training programs must evaluate trainees based on them. A notable example is in Medical Oncology, which is constantly evolving with respect to the understanding of novel targeted therapies and grade three and four toxicities associated with immune checkpoint inhibitors utilized in the management of both solid tumors and hematologic malignancies . The ACGAn additional example to illustrate disparities in cognitive bias and ACGME-defined clinical milestones used for the purposes of evaluation and promotion is within the subspecialty of Nephrology. It is imperative that trainees achieve competency in the diagnosis and management of acute kidney injury, including prerenal etiologies, such as volume depletion, intrinsic causes such as the myriad types of glomerulonephritis and tubulointerstitial injury, and postrenal causes such as obstructive uropathy. In addition, fellows must achieve sufficient training and experience with regard to the management of chronic kidney disease and its attendant complications and should develop confidence with regard to both conservative management and renal replacement therapy in patients with more advanced chronic kidney disease. Experience and training with regard to renal replacement therapies should encompass conventional hemodialysis, continuous renal replacement therapy, and peritoneal dialysis. The faculty in nephrology fellowship programs must also provide sufficient guidance and constructive feedback when training fellows to perform common nephrology procedures, including renal biopsy and temporary dialysis catheter placement. Nephrology faculty still must master the art of instilling confidence in their trainees when performing these procedures while, at the same time, always perform due diligence in ensuring patient safety. The same holds true with regard to the diagnosis and management of both acute and chronic kidney disease, in both inpatient and outpatient settings. The examples of knowledge and skills listed above, which nephrology trainees must master provide a framework upon which milestones may be tailored for renal fellowship programs. For faculty in Nephrology fellowships, the idea of using the milestones as objective criteria for the determination of promotion or remediation of fellows is still in its infancy. In addition, feedback offered must be both constructive and specific. Feedback that is vague and provides no suggestions for improvement is counterproductive to the growth of knowledge and skills in trainees.Although the ACGME has defined clinical learning milestones in Ophthalmology residency programs, the subspecialty fellowship training positions currently have no governance by the ACGME; instead, the Association of University Professors of Ophthalmology (AUPO) is the governing body. The AUPO FCC was established for the maintenance of standards for subspecialty fellowship training in ophthalmology. While having a governing body is absolutely necessary, unfortunately, the reporting of compliance by programs with the requirements for AUPO is based on self-reporting evaluations by the program director at that program, thereby introducing the first layer of bias in an evaluation system whose aim is ultimately to give objectivity to the compliance process. With less oversight, a program director could risk a higher chance of non-compliance with program requirements. As such, a program could present future employers, insurance companies, and patients with an inaccurate impression of the professional stature of a program.The AUPO has a comprehensive list of requirements for program directors that states that program directors engage in ongoing research in the area of retina and vitreous as demonstrated by publishing in peer-reviewed journals, presentations of research material at national meetings, or both. Self-reporting, gone unregulated in many cases, maybe erroneous unless verified individually through primary source verifications. Program directors must ensure, direct, and document the adequate supervision of fellows at all times. Fellows must be provided with rapid, reliable systems for communicating with supervising faculty. In some programs where a program director has an adjunct or partial academic appointment, it is difficult to quantify how that program can be in compliance with accreditation and quality metrics.To illustrate, an eye examination room with a slit lamp should be easily accessible in the hospital; however, this is often not available in poorly equipped hospitals and poorly funded hospitals. There must be access to current diagnostic equipment, including ultrasonography and fluorescein angiography. In certain clinics, this equipment is outdated, even nonfunctional, and in some cases, an outside contractor with little or of questionable credentials is scheduled to periodically perform these tests when the academic center is not adequately funded or has poor departmental leadership unable to secure funds to buy basic equipment. This would apply particularly to the provision of fluorescein angiography and modern ultrasonography equipment, equipment essential to the functionality of any vitreoretinal fellowship.With respect to the broad ACGME-defined milestone of scholarly activity, programs are supposed to track and evaluate a resident and fellows' progress with respect to quality improvement, clinical and translational research, and didactic activity involvement. The scholarly activity milestone by the ACGME is a mandatory one that trainees participate in a minimum of 100 hours of didactic instruction, including seminars, lectures, and approved basic science courses, of which at least 50 hours will be in the parent institution. All too frequently, these requirements are not met due to a lack of oversight by the program director, poorly motivated fellows with inadequate supervision, and extensive distances between clinical sites whereby a functional program is not attainable. The standards also require that a fellow should attend local and regional conferences relevant to vitreoretinal diseases and that research activities are required of all retina and vitreous fellows; however, in lower-tier programs who claim to have these credentials, there is no direct verification of the credibility of this information. Even though the program must meet or exceed RRC requirements for the teaching of ethics in residency and fellowship programs, this is difficult to comply with in situations where a program director spends the bulk of time in independent private practice. Institutional biases have been shown to take a psychological toll and contribute to physician burnout . Recent Scholarly activity and quality improvement projects as a key educational milestoneThe concept of quality improvement is a valuable and essential educational tool in training programs and general medical practice. The emphasis to engage in quality improvement projects has become a focal point embedded within the milestones project. These projects encourage introspection, team building, and humility within a department at all levels of training and expertise. By accomplishing the task of systems improvement respect through quality improvement projects, a culture of safety and enhanced communication is realized. Secondary outcomes that integrate both patient safety and the maximization of institutional resources ultimately creates better patient outcomes and enhances the synthesis of complex clinical concepts from an educational perspective. For the purposes of institutional and educational improvement, the Institutional Review Board (IRB) is an incredibly valuable resource in supporting such endeavors as retrospective studies. An example is a large academic cancer center being mindful of the appropriate use of intravenous immunoglobulin (IVIg) in patients with hypogammaglobulinemia . ScholarNeed for uniform standards, including remediation, probation, and termination, in post-graduate training programsThe process for hospital graduate medical education (GME) committees in formal assessments and promotional decisions allows faculty to ensure the trainee is achieving requisite educational advancements. Trainees perceived to be achieving the specialty or sub-specialty milestones are considered in "good standing." However, due to a lack of standard definitions of satisfactory standing, trainees who have been subjects of cognitive bias may become easy targets for retaliation by faculty . A commoA significant ACGME core program requirement is, "Be responsible for monitoring fellow stress, including mental or emotional conditions inhibiting performance or learning, and drug- or alcohol-related dysfunction." A program director and leadership have a moral and ethical responsibility to ensure that the training environment and the culture of a department and sponsoring institution are conducive to learning . InstituIt is not uncommon for a diligent trainee to be selectively blamed for negative repercussions resulting from institutional disorganization, such as an overbooked clinic, for example. Due to a corrosive environment and institutional disorganization, the program director may decide to believe negatives that are otherwise entirely divorced from reality. Learning in such a hostile environment is often exceedingly difficult for a trainee. Scenarios such as these violate the ACGME core milestones requirements to "administer and maintain an educational environment conducive to educating trainees in each of the ACGME competency areas" and "the physician faculty must meet professional standards of ethical behavior" .The Stroop effect was first described in the field of cognitive psychiatry by Dr. John Ridley Stroop in 1935, when studies were found to evaluate interference in the reaction times of a task. The working theory behind the Stroop effect is the mind quickly interprets the semantic meaning over the actual meaning. As such, a faculty member with a strong positive or negative predisposition may have difficulty in deciphering information on a milestone due to extraneous tangential information. The Stroop effect can be characterized as either "interference," in which one cognitive operation degrades the perception of another, or "facilitation," in which a cognitive operation can enhance the perception of the same task .A vast number of prior studies have displayed a propensity for implicit bias against those trainees with disabilities. For example, disabilities such as Asperger's syndrome, hearing impairment, a mobility issue, or a speech impediment can often be magnified into an “incompetency” and affect evaluations if a supervising attending has a particularly strong negative cognitive bias towards those with disabilities. This highlights the importance of raising awareness, educating, and even performing standardized testing routinely among supervising faculty about such biases, thus mitigating against the effects of cognitive bias as much as possible .Institutions sponsoring post-graduate training programs have an arduous task with respect to creating fair and standardized evaluation and promotion standards. During training, learners come from diverse cultural, emotional, and psychological backgrounds, which could subconsciously affect an evaluator's judgment. By acknowledging both the institutional and cognitive limitations in creating more objective evaluation standards consistent with the ACGME-sponsored milestones, a more inclusive and fertile ground for education and mentorship could be established.It is apparent that sponsoring institutions may require additional safeguards from the risk of institutional nepotism. There are various strategies to accomplish this, including the neuropsychological testing of faculty, assigning each trainee an academic advisor who is faculty at a separate ACGME-accredited program, and Cognitive Bias Modification Therapy (CBMT) for faculty.


Lymphovascular invasion (LVI) is a vital risk factor for prognosis across cancers. We aimed to develop a scoring system for stratifying LVI risk in patients with breast cancer.A total of 301 consecutive patients  with breast cancer confirmed by pathological reports were retrospectively evaluated at the authors’ institution between June 2015 and October 2018. All patients underwent contrast-enhanced Magnetic Resonance Imaging (MRI) examinations before surgery. MRI findings and histopathologic characteristics of tumors were collected for analysis. Breast LVI was confirmed by postoperative pathology. We used a stepwise logistic regression to select variables and two cut-points were determined to create a three-tier risk-stratification scoring system. The patients were classified as having low, moderate and high probability of LVI. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of the scoring system.Tumor margins, lobulation sign, diffusion-weighted imaging appearance, MRI-reported axillary lymph node metastasis, time to signal intensity curve pattern, and HER-2 were selected as predictors for LVI in the point-based scoring system. Patients were considered at low risk if the score was < 3.5, moderate risk if the score was 3.5 to 6.0, and high risk if the score was ≥6.0. LVI risk was segmented from 0 to 100.0% and was positively associated with an increase in risk scores. The AUC of the scoring system was 0.824 .This study shows that a simple and reliable score-based risk-stratification system can be practically used in stratifying the risk of LVI in breast cancer. Identification of clinically predictive and prognostic factors is considered as an important issue in treatment evaluation of breast cancer. The first study on the prognostic significance of peritumoral lymphovascular invasion (LVI) in breast cancer was reported in 1964 , and LVIRecently, a preliminary study used nomogram to predict the presence of LVI based on multiparametric magnetic resonance imaging (MRI) and pathological reports . HoweverThis retrospective study was approved by the Ethics Committee of the first people’s Hospital of Kashi area, and the patient’s informed consent was waived. We reviewed a total of 301 consecutive female patients  with biopsy-proven solitary breast cancer admitted to the radiology department between June 2015 and October 2018. All patients underwent a 1.5 T MRI scan before surgery. Patients with complete clinicopathological characteristics. All patients had received no neoadjuvant therapy prior to operation. Patients with previously-diagnosed breast cancer or incomplete clinical records were excluded.Clinicopathological features were collected including age, ER, PR, HER-2, Ki-67 index and histological subtypes. Positive ER or PR was recorded by immunohistochemistry when at least 1% of the tumor cell nuclei showed staining for ER or PR, respectively . HER-2 w2). Axial dynamic contrast-enhanced (DCE) MRI was performed using the volumetric interpolated breath-hold examination (VIBE) fat-suppression sequence , 55 dynamic phases, 7.3 s per phase, a total of 405 s. At the second phase of DCE scan, a bolus of 0.1 mmol kg− 1 of gadodiamide  was injected into the antecubital vein at a rate of 3 mL/s, followed by a 30 mL saline flush. After the DCE scan, axial and coronal T1-weighted fat-suppression contrast-enhancement sequences were obtained .Preoperative breast MR imaging is a routine practice in our Institution. The MR imaging was performed in the prone position using a dedicated four-channel double-breast coil with a 1.5 T system . Bilateral whole-breast MR imaging was performed using the following sequences and parameters: axial 3D gradient echo (GRE) Dixon T1-weighted sequence . Axial T2-weighted short tau inversion recovery (STIR) . Axial DWI was obtained with SE sequence , tumor size (maximum diameter), margins (well- defined or ill- defined), lobulation sign (absence or presence), spiculation sign (absence or presence), MRI-reported axillary lymph node metastasis (ALNM) , DWI appearance (slight/moderate hyperintensity or marked hyperintensity), time-intensity curve (TIC) patterns . A 3 × 3 pixel standard-sized regions of interest (ROI) was selected within the areas of obvious intense enhancement in the tumor. TIC was generated. Metastatic axillary lymph nodes were nodes with major axis > 10 mm and hilus of lymph node disappeared.LVI was evaluated on routine hematoxylin–eosin-stained sections according to the method of Pinder et al. . LVI wasp values < 0.05 were considered significant. For each significant variable a regression coefficient was obtained. Factors significantly associated with breast LVI in univariable and multivariable logistic regression analysis using stepwise method are listed in Table We used a stepwise logistic regression to select variables. Variables in the stepwise analysis with p <  0.05 were considered significant.R version 3.2.3 was used for statistical analysis. As for continuous variables, data were expressed as mean ± standard deviation (SD), while for categorial variables, data were expressed as counts and percentages . Continuous and categorial variables were compared by independent t tests, Mann-whitney U test, or Chi-square, if appropriate. The AUCs of logistic regression model and scoring system were compared with Delong test. A Among the 301 lesions, 106 35.2%) were invasive ductal carcinoma (IDC) , 149 (49.5%) were IDC , 46 (15.3%) were ductal carcinoma in situ (DCIS). In total, 104 (34.6%) patients  had LVI and 197 (65.4%) patients  without LVI. Comparison of clinicopathologic and radiological features between patients with and without LVI is shown in Table % were inBy multivariate logistic regression analysis, seven variables were significantly related to LVI and were assigned scores for the final prediction rule: margins , DWI appearance (marked hyperintensity [1.0 points]), TIC pattern , MRI-reported ALNM , HER2  (Table .0 pointsp = 0.239) . The proposed scoring system achieved an AUC of 0.824 (95%CI: 0.776–0.872). There were no significant AUC differences between the logistic regression model and the scoring system (39) Fig. . Table 4For example, patient 1 aged 59 years, who had a tumor in her right breast, location in the.upper-outer quadrant, with maximum diameter of 19 mm, well-defined margins, absence of lobulation sign, marked hyperintensity on DWI images, type I TIC, and no ALNM Fig. a-f. BiopIn this present study, we proposed a risk-stratification score system based on MRI-derived and histopathologic features to predict LVI in breast cancer. The system incorporated six predictors including tumor margins, lobulation sign, MRI-reported ALNM, DWI appearance, TIC pattern, and HER-2 status. Our results showed that the scoring system for predicting breast LVI had good discrimination . Within the system, patient’s risk for LVI was categorized as low (< 3.5 points), moderate (3.5–6.0 points) or high (≥6.0 points).Risk stratification scoring system has been widely created to aid in clinical decision-making and potentially improve the patients management –22. To oWe found that MRI findings including tumor margins, lobulation sign, MRI-reported ALNM, DWI appearance, and TIC pattern were important risk factors for the prediction of breast LVI. We found tumor with LVI usually had morphological characteristics such as ill-defined margins, and lobulation sign. Tumors with irregular or spiculated or lobulated margins have a significantly higher microvessel density than tumors with smooth margins since the morphology is associated with a more aggressive behavior in breast cancer .P = 0.008), which was in line with this study [P  <  0.001), which was in line with a previous study performed by Ugras et al. [A review has shown that the presence of LVI correlates closely with locoregional lymph node involvement . Althougis study . Malignais study . DCE-MRIis study . HER-2 gis study , increass et al. .This study also has some limitations. Firstly, we evaluated DWI appearance instead of ADC values for LVI prediction because we didn’t measure ADC in routine practice. Secondly, this was a retrospective study. Thirdly, this study didn’t include multifocal or multicentric carcinoma. Finally, we didn’t test this scoring system in a validation cohort, which may limit the transfer of our system to other institutions.In summary, our MRI and HER2 based scoring system can be applied in a preoperative setting. The system can be used to stratify LVI risk in breast cancer patients, which is helpful for clinical decision-making regarding tumor staging, treatment planning, and prognosis assessment. Patients with LVI may require for adjuvant therapies because of the high risk of recurrence and metastasis.