Rewriting the 10 commandments: Fontan candidacy in the modern era

Real-world treatment patterns and outcomes in a national study of veterans with Waldenström macroglobulinemia, 2006-2019.

The changing epidemiology of cardiac allograft rejection has prompted many to question the yield of surveillance endomyocardial biopsy (EMB) in heart transplantation (HT) patients. We sought to determine the yield of EMB in the modern era. We evaluated 2597 EMBs in 182 consecutive HT patients who survived to their first EMB. The EMBs were categorized as asymptomatic or clinically driven and were compared based on era of antiproliferative therapy use at our center (early azathioprine era: 1990-2000 vs modern mycophenolate era: 2000-2011). In the modern era, patients had a higher prevalence of risk factors for developing rejection (≥ International Society of Heart and Lung Transplantation grade 2R); however, the frequency of rejection was decreased at all times (0-6 months: 60.2% vs 21.5%, P < 0.001, 6-12 months: 26.8% vs 1.8%, P < 0.001, 12-36 months: 32.3% vs 10.5%, P = 0.006). The yield of asymptomatic EMB decreased in the modern era between 0 and 6 months (10.9% vs 3.12%), 6 to 12 months (17% vs 0%), and years 2 to 3 (6.1% vs 1.5%). In the early era, the odds ratio of rejection during asymptomatic EMB compared to a clinically driven EMB was 0.47 (95% confidence interval, 0.31-0.71) and was decreased in the modern era (0.17 [0.07-0.42], P = 0.04). The probability of detecting rejection on asymptomatic EMB was significantly reduced in the modern era, even after adjustment for tacrolimus and induction therapy (1% vs 8%, P < 0.001). The clinical yield of surveillance EMB has decreased in the modern era. The EMB in asymptomatic patients longer than 6 months after HT warrants further scrutiny.

C aracterísticas y supervivencia técnica de la hemodiálisis domiciliaria en la Comunidad Valenciana (1976-2020)

Characteristics and technical survival of home hemodialysis in the Valencian Community (1976–2020)

Developing and maintaining a definitive list of scarce and essential skills is crucial for the TVET sector. TVET colleges should swiftly work on ‘workplace basics’ skills to attract different industries for their students. The purpose of this study was to inspect how TVET colleges prepare Civil Engineering students with occupational skills relevant for modern engineering era. Descriptive research design was used to describe trends of connection with the help of secondary data. This research design assisted to describe how TVET colleges prepare its Civil Engineering students with occupational skills relevant for modern engineering era. This study adapted Carnevale’s (1990) workplace basics as a conceptual framework. The collective findings revealed that TVET colleges faced several hurdles in their quest to equip Civil Engineering students with the necessary skills that would make them good candidates for taking up employment in industries against the backdrop of changes being wrought by the modern era. Among the recommendations, a call for professional teacher development with focus to 4th industrial revolutionskills is made and that SETAs should support that initiative. Also such skills should be intensified in such a way that it may be easy to adapt to the 5th industrial revolution upon its arrival.

Injury recidivism is a clinical term defined as the recurrence of traumatic injuries from temporally distinct events, whereas multiple injuries correspond to skeletal injuries to more than one body region. The analysis of these dynamics can lead to a better understanding of the individual’s way of life and social environment. The present investigation examines the rates of multiple injuries, and in particular their distribution according to sex and age-at-death, as well as their association with stress markers, among 200 skeletons from Milan covering four historical periods (roman, medieval, modern, and contemporary eras), equally divided between sexes. In addition, injury recidivism was investigated in the sample and three cases were identified and detailed as case studies. As a result, multiple injuries were more frequent in the Medieval period (41%), followed by the Contemporary (25%), Roman (19%) and Modern eras (15%). Statistical analyses showed a significant association between multiples injuries and male sex, but not with age-at-death or stress markers. The three cases of recidivism included one female from the modern era and two males from the Medieval period. The analysis of the injuries and their recurrence permitted to improve our understanding of the individuals’ social environment and hypothesize on their causes (accidents/occupational work, and interpersonal violence).

Objective: Rates and determinants of first-line antiretroviral (ARV) discontinuation or change in prescribed regimen were assessed between old (pre-2006) and modern (post-2006) era stratified by dosing frequency [(once daily (QD) versus twice or more daily (BID+)]. Methods: A single-center retrospective cohort study was conducted. All adult HIV patients initiating ARVs from January 1995-November 2015 were included. Patients were stratified by old- or modern-era and by dosing frequency. The primary outcome was rate of ARV therapy discontinuation or change in initial regimen. The secondary outcome was reason for discontinuation. Results: 1,127 patients were included from the old (n=621) and modern era (n=506). Modern-era patients were more likely to receive QD regimens (p<0.001) and had increased viral suppression at the last recorded testing than oldera patients (70.9% vs. 43.2%, p<0.001). Modern-era and QD patients had better adherence and treatment duration. Patients on integrase inhibitor (INSTI)- and NNRTI-based therapy had longer treatment durations and better ARV adherence. Risk factors for treatment switch or discontinuation included old-era therapy, IDU and PI+NRTI treatment. Older ages and immigrants were less likely to discontinue therapy. Common reasons for treatment discontinuation included changing treatments to improve regimen profile, gastrointestinal side effects, and neuropsychological issues. Conclusion: In patients initiating first-line ARV, risk of discontinuation or regimen changes has diminished in the modern-era with QD, INSTI- or NNRTI-based regimens. More attention to high risk patients including IDU is advised in attempts to improve outcomes. These findings provide ‘real world’ support for current clinical practice guidelines.

Transcatheter aortic valve implantation (TAVI) has emerged as an effective treatment for high-risk patients with severe aortic stenosis (AS). The aim of our study was to compare the prevalence, characteristics and outcomes of high-risk patients treated prior to and after the availability of TAVI in our high-volume surgical institution. Among 879 consecutive patients treated 2 years before ('pre-TAVI era') and after ('modern era') the availability of TAVI in our institution, 83 patients were at high risk [defined by logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) >20%]. Among all patients treated for severe AS, the prevalence of high-risk patients was higher in the modern era (12.7 vs 4.9%, P < 0.0001). In the modern era, high-risk patients were treated by TAVI in 89% of cases. Despite similar logistic EuroSCORE (34.9 vs 34%, P = 0.96), the clinical characteristics of these patients have evolved: high-risk patients in the modern era were older (85.3 ± 5.9 vs 78.5 ± 6.5 years, P = 0.0005) and presented more frequently with New York Heart Association class III-IV (92.3 vs 61.1%, P = 0.003), while high-risk patients treated by surgical aortic valve replacement in the pre-TAVI era presented more frequently with a critical preoperative status (33.3 vs 7.7%, P = 0.01), lower left ventricular ejection fraction (41 ± 14 vs 49 ± 15%, P = 0.05) and a history of recent myocardial infarction (27.8 vs 6.1%, P = 0.02). The overall 1-year survival was not different for high-risk patients treated in the pre-TAVI era or in the modern era (61 ± 11 vs 68 ± 6%, P = 0.52). The availability of TAVI has increased the prevalence of high-risk patients treated for severe AS and changed the clinical features of this kind of patients who were rarely surgically treated before. The 1-year survival was similar between pre-TAVI and modern eras.

In this Modern era, human being identic with positivistic and materialistic thinking. In this step human out of religious and philosophic thinking. That gives impact to morality that lose from believe in God. This is urgency of this research at modern global era. Writer use philosophical approach and critical method. The result of this research is characteristic of Gus Dur ethic it’s religious-rational. The foundation of Gus Dur ethic is religious teaching, God gives human some of excess that are reason, moral and feel. From that, human have to responsibility to keep universe especially to human being, not to self-interest. Gus Dur ethic that based on religious and ratioanl approach is appropriate in this modern era, especially at Indonesian state, because Gus Dur is the figure that rise up Indonesian Islam (Islam Nusantara)

HL-526 Improved Survival of Elderly Patients With Classical Hodgkin Lymphoma (cHL) in the Modern Era - A SEER-Registry Analysis

According to a number of myths, the cultural effects of globalization and modernization have not really impeded East Asian countries' efforts towards cultural heritage preservation. In tandem with this, many “fascinated” members of the African intelligentsia view Eastern Asian nations such as China, South Korea, Japan, Singapore, Malaysia, and Thailand among others as true models to be emulated by their nations in the realm of cultural heritage preservation. This chapter examines the extent to which this thesis is plausible, through a critical study of the impact of globalization and modernization on cultural heritage preservation in China and Nigeria. The chapter begins by exploring the question of cultural preservation in an era of modernization and cultural globalization and ends up assessing the degree to which China and Nigeria's efforts towards cultural heritage preservation have been affected by cultural globalization and a West-dominated model of modernization.

This is, for the most part, the history of the development of curative combination chemotherapy for Hodgkin's disease, and its consequences, from 1963 up to the early 1990s [the MOPP (nitrogen mustard, oncovin, procarbazine, prednisone) programme]. Coupled with radiotherapy, it had a major impact on the management of the disease. It is also heavily weighted towards the description of the events that occurred at the Medicine Branch of the National Cancer Institute (NCI) in Bethesda, MD, USA, between 1963 and the early 1990s. To this is added a brief description of the follow-up development of the ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) treatment drug programme by the group in Milan, Italy. The latter added significantly to the therapeutic armamentarium available to physicians in the 1970s and beyond. This selective history is perhaps justified because, although the focus of the studies discussed below was on Hodgkin's disease, there was a more important issue involved. A new breed of cancer investigators in the 1960s had been addressing the generic question of whether or not cytotoxic chemotherapy was ever capable of curing patients with any type of advanced malignancies. The answer would turn out to be 'yes', and this affirmative answer enabled chemotherapy to be used in many other tumours and, notably, in the adjuvant setting after treatment of apparently localized disease. The question was addressed in two important human models, childhood acute leukaemia (Frei & Freireich, 1965) and Hodgkin's disease, and used combination chemotherapy, a concept that deviated from the practice of the time. The response in the academic community to this radical departure from dogma was initially quite negative. The protected environment of The Medicine Branch, at the Clinical Center of the NCI, facilitated studies in both diseases, under the inspired leadership of Dr Emil Frei, who was Chief until 1965 (Fig 1). In recounting these events, the novelty of the approaches and study results do not seem so radical in retrospect, but they were. Dr Emil (Tom) Frei in Bethesda in the 1960s. Chief of Medicine at the NCI until 1965. Photograph from the author's collection. At the time the programmes began at the NCI, radiation therapy was already established for Hodgkin's disease patients presenting with apparently localized disease. We did not know the aetiology of Hodgkin's disease or the cellular origin of the Reed–Sternberg cell that characterizes the disease. Medical oncology, as a speciality, had not yet appeared on the scene. Physicians who would become the medical oncologists of the future worked with therapeutic radiologists and pathologists to integrate newer methods of diagnosis, staging and radiotherapy with the newly developed chemotherapy programmes and converted Hodgkin's disease from a largely fatal to a largely curable disease. For the integration of chemotherapy and radiotherapy in Hodgkin's disease, we owe a debt of gratitude to the late Henry Kaplan (Fig 2), who was unique in his field in recognizing the value of the new chemotherapy. He set in motion a brilliant series of studies of the use of MOPP and radiotherapy at Stanford University in the late 1960s and 1970s that still serve as a model of clinical investigations (Kaplan, 1962, 1966; Kaplan & Rosenberg, 1966; Kaplan et al, 1973). Curative chemotherapy had provided the missing link in the therapeutic equation. The late Harry Kaplan at Stanford in the early 1970s. Photograph from the author's collection. The group of senior faculty members from the Medicine Branch, shown in Fig 3, went on to apply these same principles to other cancers (Bagley et al, 1972; Canellos et al, 1974). The development of the CMF programme (cyclophosphamide, methotrexate and 5-fluorouracil) for breast cancer (Canellos et al, 1974) and the NCI's contract with the Istituto Tumori in Milan, Italy, to test it in the adjuvant situation helped to set in motion a similar series of events in breast cancer. The author, then Chief of Medicine at the NCI (second from right), with the senior faculty of the Branch who played a role in advancing the studies on all the lymphomas. Left to right: Drs George Canellos, Bruce Chabner, Phillip Schein, the author and Robert Young (about 1970). Photograph from the author's collection. The author (Fig 4) chose to end this tale in the early 1990s because, at that point, we entered a new era of treatment for Hodgkin's disease. Investigators began to focus on the problems of curing a minority of patients not cured by the initial programmes and reducing the morbidity of treatment revealed in long-term follow-up studies. A daunting task, but another story entirely. The author in the Medicine Branch of the NCI in 1968. Photograph from the author's collection. Pusey first used radiotherapy to treat Hodgkin's disease in 1902 (Pusey, 1902), only 8 years after Roentgen rays were discovered. The important observation that Hodgkin's disease spread by contiguity is owed to several investigators, most notably the Swiss radiotherapist Renee Gilbert in the 1920s (Gilbert, 1925) and the Canadian radiotherapist Vera Peters in the 1950s (Peters, 1950; Peters & Middlemiss, 1958). These observations had important implications for radiotherapy, as fields could now be shaped to encompass areas of presumed contiguous spread. By observing the natural history of the disease in large patient populations, Vera Peters (Peters, 1966) and Henry Kaplan (Kaplan et al, 1973) were able to map the patterns of spread and apply appropriate radiotherapy fields (Rosenberg & Kaplan, 1966). Although Vera Peters implied that the disease was curable (Peters & Middlemiss, 1958), it was Easson and Russell from the Christie Hospital, Manchester, UK, using her data, who first broached the subject of 'The Cure of Hodgkin's disease' (Easson & Russell, 1963). It was a sign of the pessimism of the times that the title was considered provocative and controversial. It was Kaplan who made the point that localized Hodgkin's disease could by cured by radiotherapy with finality and conducted the trials to show the doses and extent of radiotherapy necessary to cure early stages of the disease. At Kaplan's insistence, a conference of leading investigators was convened in Rye, New York, in 1966 that not only married the new histological classification developed by Lukes & Butler (1966) to treatment, but laid out the principles of staging necessary for an orderly approach to treatment. Combination chemotherapy was just in its seminal phase at this time but already the cure of localized stages with good radiotherapy was noted to be about 30%. In the early 1960s, the debate that dominated chemotherapy was not could it cure, but whether or not the palliation achievable was worth the toxicity associated with anticancer drugs. The first chemotherapy study to have an impact on the management of patients with Hodgkin's disease was published in 1963 (Scott, 1963). Eighty-nine patients with advanced Hodgkin's disease received a conventional induction course of nitrogen mustard (0·4 mg/kg), of whom 40 patients with 'satisfactory response' were randomized to receive either no further treatment or continuous treatment with the newly developed oral alkylating agent, chlorambucil. In the 16 patients who received chlorambucil, the time to relapse averaged 35 weeks compared with 11·7 weeks without further treatment. This highly significant difference in the duration of a 'satisfactory remission' provided the first useful information on alternatives in the day-to-day management of patients with Hodgkin's disease. No mention was made in this study, however, as to whether any survival benefit accrued to the patients maintained on chlorambucil. A report by Jacobs et al (1968) presented one of the first survival curves published in the modern chemotherapy era. Drug treatment in patients with advanced Hodgkin's disease was associated with a median survival of less than 2 years, with only 5% living beyond 4 years, all with evidence of disease, only slightly superior to patients left untreated for the entire course of their disease (Craft, 1940) (Fig 5). Survival curves of patients with Hodgkin's disease either untreated (Craft, 1940) or treated only with alkylating agents (Jacobs et al, 1968) before the advent of combination chemotherapy. The next major advance came with the identification of the antitumour activity of the plant-derived natural products, the vinca alkaloids. The availability of two non-cross-resistant classes of antitumour agents and the conceptual separation of induction and maintenance therapy gave impetus to a large study initiated through the combined effort of two clinical co-operative groups supported by the NCI (Acute Leukaemia Group B and the Eastern Solid Tumor Group). The principal investigator was the late Paul Carbone of the NCI's Medicine Branch (Carbone et al, 1968). Patients were randomized by disease and prior therapy to remission induction with cyclophosphamide or one of the vinca alkaloids. The objectives of this study were to compare the effectiveness of the vinca alkaloids with an alkylating agent in remission induction in lymphomas. Patients received either cyclophosphamide or placebo to maintain the remission, which enabled the effectiveness of continuous therapy to be compared with intermittent treatment with cyclophosphamide at the time of disease progression. The results of this study established the superiority of vinblastine over cyclophosphamide in patients with Hodgkin's disease. In all disease categories, the average duration of placebo-maintained remission was a remarkably short 4–6 weeks, irrespective of the drug used to induce remission. Daily oral cyclophosphamide significantly prolonged remission duration when compared with placebo, confirming the observation of Scott (1963). Remission duration with drug maintenance treatment was, however, only 32 weeks for Hodgkin's disease. Two features of this study influenced the studies designed later by NCI investigators. First, patients were separated by whether they had partial or complete remissions, a practice used to evaluate treatments in leukaemias but not generally used at that time in 'solid tumours'. Secondly, regardless of the approach to treatment, overall survival in the various subgroups in each disease category was almost identical. Those data enabled investigators at the NCI, using the first combination chemotherapy programmes, to set achieving a high complete remission rate as their major initial goal in the first combination chemotherapy programme, and to leave patients who attained a complete remission off therapy to evaluate the capacity of their new treatment programme to eradicate the tumour permanently. The appearance of vinca alkaloids was followed shortly by the discovery of the antitumour activity of the methylhydrazine derivative, procarbazine, then called ibenzmenthyzin, in Hodgkin's disease (Bollag & Grunberg, 1963; Mathe et al, 1963; DeVita et al, 1965a). The first intensive drug combination programme designed to exploit the new principles of chemotherapy in Hodgkin's disease began at the NCI in 1963 and used the combination of vincristine, methotrexate, cyclophosphamide and prednisone (MOMP) given for only 2·5 months (DeVita et al, 1965b; Moxley et al, 1967). The goal of this pilot protocol was to test the safety of combination chemotherapy in advanced Hodgkin's disease. The vinca alkaloid, vincristine, was selected over vinblastine because it has little associated marrow toxicity, and preclinical studies suggested therapeutic effects equal to vinblastine. In an era devoid of reliable methods to support patients during periods of bone marrow suppression, this was an important issue. Only 14 patients were treated with MOMP, and all were hospitalized and kept in reverse isolation. This small study showed that the approach was safe. In 1964, the MOMP programme was modified in several ways. At that time, most data on the doses and schedules of anticancer drugs in humans were derived and translated directly to the clinic from tumour-bearing mouse models. But, comparative cell kinetic data in mouse and human tumours had shown much-prolonged human tumour cell cycle times, compared with the mouse (Yankee et al, 1967; Young & DeVita, 1970; DeVita, 1971; DeVita & Schein, 1973). So, the duration of MOPP treatment was increased from 2·5 months, the standard of the time, to 6 months. And, procarbazine, by now an agent known to be active in Hodgkin's disease, was substituted for the antifol methotrexate. Each drug was used in its optimal dose and schedule. This new programme was named MOPP ('M' for nitrogen mustard, 'O' for oncovin, the brand name for vincristine, and 'PP' for procarbazine and prednisone). Cyclical administration every 28 d was introduced, and the interval selected between cycles was the narrowest possible to allow for recovery of the most sensitive normal target tissue, the bone marrow. Again, cell kinetic studies on the mouse bone marrow, compared with humans, showed that, like mouse and human tumours, the kinetics of human marrow were also quite prolonged compared with the mouse (Yankee et al, 1967; DeVita et al, 1969a; Young & DeVita, 1970; DeVita, 1971). Thus, for patients whose tumour, unlike leukaemia, infrequently involved bone marrow, adjustments in schedules were made to introduce wider intervals between treatments than previously allowed. In 1967, the results of the use of MOPP in the first 43 chemotherapy-naïve patients were reported in abstract form, and formal results were published in 1970 (DeVita et al, 1970). An 80% complete remission rate was noted. This was a fourfold increase over results achieved with the best use of single agents of the day, and those remissions proved durable and appeared to influence survival. The survival of treated patients was impressively different from those treated with single agents (Fig 6). British investigators, under the leadership of the late G. Hamilton Fairley, confirmed the effectiveness of combination chemotherapy with a modified version of MOPP (Nicholson et al, 1970). Others followed suit in either controlled (Huguley et al, 1975) or uncontrolled (Frei et al, 1972a; Moore et al, 1973) studies. While the Stanford group confirmed the NCI results, their concern with the neurotoxicity of vincristine led them to recommend capping the dose at 2 mg total dose. This widely practised dose adjustment negatively affected the dose intensity of vincristine in all future studies of MOPP (Moore et al, 1973). Life table analysis of survival for the entire group of 43 patients (solid line) and the 35 patients achieving a complete remission (CR; dotted line). Figures in parentheses next to each point indicate the number of patients at risk for that interval. From the original MOPP trial (DeVita et al, 1970). Published with permission. When the NCI investigators later reported on the long-term follow-up of the MOPP treatment of the first 198 patients, the initial results were maintained (DeVita et al, 1980; Longo et al, 1986) (Fig 7). Of 198 patients, 159 (80%), achieved a complete remission with a median of three treatment cycles. All 23 patients without symptoms attained complete remission, compared with 78% of the symptomatic patients. This difference was highly significant, and only one asymptomatic patient had relapsed in subsequent years. Plot of remission duration in 198 patients with advanced Hodgkin's disease treated with MOPP at 20 years follow-up from Longo et al. (1986). Reprinted with permission from the American Society of Clinical Oncology. Sixty-three per cent of patients achieving complete remission, who were at risk for longer than 10 years, remained disease free. Because 80% of the entire treated population achieved a complete remission, the proportion of all treated patients who remained free of relapse at 10 years and beyond was 54·6%. The vast majority of relapses occurred within 42 months after cessation of therapy. Two features had a powerful effect on outcome, the absence of symptoms and the dose delivery rate of the drug vincristine. The next question posed was whether maintenance drug therapy would be beneficial after achieving a complete remission, as 35–50% of patients relapsed by the fifth year of follow-up. The first such study was also conducted at the NCI (Young et al, 1973). After achieving complete remission, patients were randomly allocated to intermittent cycles of carmustine (the then new nitrosourea, BCNU) or no therapy or intermittent cycles of MOPP. Maintenance treatment was given for 15 months. When the results of this study were reported in 1973, and reanalysed in 1980, there were no significant advantages for either continued intermittent MOPP or intermittent carmustine therapy. Seven other studies designed to test the usefulness of maintenance therapy have been conducted, also with no long-term positive effects noted (Coltman et al, 1976; DeVita, 1981). An important biological principle, related to the issue of de novo resistance to chemotherapy, was first observed from the retreatment of relapsed patients. Only five out of 17 patients whose initial complete remission was less than 1 year in duration achieved a second complete remission (29%), compared with 14 out of 15 patients whose initial complete remission was 1 year or longer (93%), a statistically significant difference (P = 0·001) and, once again, remissions in this latter group were durable (Fisher et al, 1970). Overall, survival was significantly improved in those patients who achieved second remission over those who did not achieve a second remission (P = 0·005). Retained sensitivity to MOPP in patients who stayed in remission in excess of 1 year was a novel observation at the time and indicated that these patients were 'almost cured' by the induction programme, and might benefit from future intensification of treatment. This has proven to be the case in the modern era. The relative insensitivity of the tumour of patients who experience short remissions (< 12 months) suggested that the primary cause of treatment failure in this group was the presence and overgrowth of cells resistant to the drugs in the MOPP programme at the time of diagnosis. More importantly, the observation on retained sensitivity after a long drug-induced remission has carried over to virtually all advanced cancers where complete remissions in response to drug combinations are attainable, and illustrates an important and generally unexplained biological principle that is still under investigation (Fisher et al, 1970; Viviani et al, 1990; DeVita, 1991; Longo et al, 1992). The impressive survival curves in MOPP-treated patients published in 1970 indicated that it was possible to cure advanced Hodgkin's disease with combination chemotherapy (DeVita et al, 1970). As the capacity to cure early-stage disease with radiotherapy was limited, the cure of advanced disease made it ethically possible to ask the question whether the use of chemotherapy alone, in lieu of radiotherapy, would improve the cure rate when the tumour volume was low. A trial testing this hypothesis was initiated at the NCI in 1978, comparing MOPP therapy alone, in laparotomy-staged patients, with subtotal nodal irradiation therapy (Longo et al, 1991a). MOPP, indeed, proved superior to Only one other similar trial has been et al, 1992). Although the results are only they have made it possible to chemotherapy as an to radiotherapy in early-stage patients, an approach that is now under investigation in the modern era. a population of patients available for study, other important observations related to the use of chemotherapy were first made in these initial MOPP studies 1981). the first evidence of the long-term effects of cancer agents in cured humans et al, 1972; DeVita et al, the first evidence of from cytotoxic drugs & DeVita, 1973) and the impact of chemotherapy on et al, the first evidence of the recovery of the unique to Hodgkin's disease, with therapy that was in (Fisher et al, and the identification of unique to cancer patients at that time, the first and treatment of in an (DeVita et al, These conducted by a single group at one over 20 years to as by the time it to the results of all the studies designed in the 1960s and 1970s. It is a to the of a in clinical It also led to the first cure of the most of known as the large cell with a of the MOPP programme, another story in (DeVita et al, Although the MOPP studies established that an advanced cancer of a major in could be cured by combination chemotherapy, of patients did not achieve complete remission after MOPP, and of complete the availability of new in the late 1960s and investigators began to and test new The known as ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) was developed at the Istituto Tumori in Milan, et al, on evidence of the of all drugs and their sensitivity with MOPP (Frei et al, et al, et al, A randomized trial was in to test whether ABVD chemotherapy could induce a complete remission rate with that of MOPP chemotherapy et al, Overall, cycles of either a of complete remissions, and this had an influence on the from and survival This study showed that ABVD chemotherapy was as as MOPP in durable remissions in advanced Hodgkin's disease. effects were similar in both drug but the later were therapy to the development of acute leukaemias in the alkylating MOPP the effect of and irradiation to the and proved to be the major with from both the NCI and the group showed that patients who did not achieve a complete remission after either MOPP or ABVD showed of tumour after the first cycles of chemotherapy, or within a months after an initial complete remission, and that a of these patients could be by the chemotherapy. To the of the availability of two non-cross-resistant drug investigators at the Cancer Institute designed was called the MOPP and ABVD that cycles of MOPP and ABVD to be given not for 6 months, the but over 12 months. By previously patients were randomized to receive either cycles of MOPP or 12 months of et al, Although there were no in two non-cross-resistant drug combinations appeared to a superior initial response to MOPP for 12 months, however, led to a in dose for vincristine, which had been given for that duration of time, and this have affected the response rate to MOPP. study of non-cross-resistant chemotherapy, at about the same time at the NCI, had a different It compared MOPP, this time in its with 6 months of MOPP with and a combination of drugs that had also been shown to be an to MOPP (Longo et al, The results showed no for chemotherapy when MOPP was given at & published a model to the failure of chemotherapy to cure more patients with advanced model that tumour cells towards drug resistance before to chemotherapy, and at cell that would be below the of of the Drug resistance was to their to be in all tumours to a or at the time of diagnosis. This was, combination chemotherapy was in by resistant with drugs. was to apply all available drugs this was not approaches were the next best the information in the two trials from the NCI and Milan, they the results of the study as clinical of their This set in motion a of clinical trials of delivery of the two non-cross-resistant the that dominated clinical trials in Hodgkin's disease & DeVita, The test of the hypothesis in Hodgkin's disease came from the Cancer and Leukaemia This co-operative group MOPP ABVD MOPP with ABVD in and patients (Canellos et al, 1992). As was the case in the NCI study, the study confirmed that a combination programme in this given in be as as therapy. To the early long-term follow-up data have shown any survival the three treatment and the practice is the use of a standard 1991; Canellos & 40 years after the development of combination chemotherapy, Hodgkin's disease patients are cured in 80% of and from the disease have in the At 15 years from the end of treatment, a patient has a risk of of a of treatment than of Hodgkin's disease patients receive combination chemotherapy and radiotherapy (Longo et al, and those that those with long first remissions, are with intensive treatment programmes, with cell as support for marrow The for newer combinations of more less drug combinations on with only one programme from the toxicity of both MOPP and ABVD et al, We we know that the Reed–Sternberg cell is a B although this has not helped and the aetiology of the disease still by the Reed–Sternberg cell are however, for either or derived from but of the latter methods has advanced in a clinical situation by a of treatment cell used in the of that is with toxicity with less have an in as a therapeutic approach of The set in motion by the cure of acute childhood leukaemia and Hodgkin's disease has maintained its A of advanced cancers be cured by combination chemotherapy, and the of chemotherapy as an to has the management of such as those of the breast and As to and drugs for them the there is for a more of treatment that a on the patient with cancer and, most cancers from a to a disease, like Hodgkin's disease & DeVita,

The management of arterial injury at the thoracic outlet has long hinged on the fundamental principles of extensile exposure and vascular anastomosis. Nonetheless, treatment options for such injuries have evolved to include both endovascular stent placement and temporary vascular shunts. The purpose of this study was to evaluate our recent experience with penetrating cervicothoracic arterial injuries in light of these developments in trauma care. Patients with penetrating injuries to the innominate, carotid, subclavian, or axillary arteries managed at a single civilian trauma center between 2000 and 2013 were categorized as the modern era (ME) cohort. The management strategies and outcomes pertaining to the ME group were compared to those of previously reported experience (PE) concerning injuries to the innominate, carotid, subclavian, or axillary arteries at the same institution from 1974 to 1988. Over the two eras, there were 202 patients: 110 in the ME group and 92 in the PE group. Most of the injuries in both groups were managed with primary repair (45% vs. 46%; p = 0.89). A similar proportion of injuries in each group was managed with anticoagulation alone (14% vs. 10%; p = 0.40). In the ME group, two cases were managed with temporary shunt placement, and endovascular stent placement was performed in 12 patients. Outcomes were similar between the groups (bivariate comparison): mortality (ME, 15% vs. PE, 14%; p = 0.76), amputation following subclavian or axillary artery injury (ME, 5% vs. PE, 4%; p = 0.58), and posttreatment stroke following carotid injury (ME, 2% vs. PE, 6%; p = 0.57). Experience with penetrating arterial cervicothoracic injuries at a high-volume urban trauma center remained remarkably similar with respect to both anatomic distribution of injury and treatment. Conventional operative exposure and repair remain the cornerstone of treatment for most civilian cervicothoracic arterial injuries. Therapeutic study, level V.

Head and neck cancer is a common malignancy frequently treated with chemotherapy and radiotherapy. Studies have shown an increased risk of stroke with the receipt of radiotherapy, but data on stroke-related mortality are limited, particularly in the modern era. Evaluating stroke mortality related to radiotherapy is vital given the curative nature of head and neck cancer treatment and the need to understand the risk of severe stroke in this population. We analyzed the risk of stroke death among 122,362 patients (83,651 patients who received radiation and 38,711 patients who did not) with squamous cell carcinoma of the head and neck (HNSCC) diagnosed between 1973 and 2015 in the SEER database. Patients in radiation vs. no radiation groups were matched using propensity scores. Our primary hypothesis was that radiotherapy would increase the hazard of death from stroke. We also examined other factors impacting the hazard of stroke death, including whether radiotherapy was performed during the modern era when IMRT and modern stroke care were available as well as increased HPV-mediated cancers of the head and neck. We hypothesized that the hazard of stroke death would be less in the modern era. There was an increased hazard of stroke-related death in the group receiving radiation therapy (HR 1.203, p = 0.006); however, this was a very small absolute increase, and the cumulative incidence function of stroke death was significantly reduced in the modern era (p < 0.001), cohorts with chemotherapy (p=0.003), males (p=0.002), younger cohorts (p<0.001) and subsites other than nasopharynx (p=0.025). While radiotherapy for head and neck cancer increases the hazard of stroke death, this is reduced in the modern era and remains a very small absolute risk.

Background: Combined heart–liver transplantation (CHLT) offers long-term survival comparable with isolated heart transplantation. National use keeps rising, and 2019 was the first year adults with congenital heart disease (ACHD) represented &gt; 50 % of all CHLTs. Whether these modern ACHD candidates reach transplant in poorer condition—and how their increasing complexity affects outcomes—remains uncertain. Methods: UNOS STAR files captured every adult CHLT (2000-2024). A Pre-modern era (2000-2018) was contrasted with a Modern era (2019-2024). Wilcoxon and Chi-squared tests compared characteristics; Kaplan–Meier curves and multivariable Cox models—including a prespecified Modern era × ACHD interaction—evaluated 90-day and 1-year mortality. Thirty-day conditional survival localised excess risk. Results: Among 586 heart-liver transplants from 2000–2024, annual volume more than doubled after 2019, rising from ~30 to over 70 per year (Image 1) . ACHD recipients also increased from 28% to 55% in 2019. Modern recipients were younger (median 43 vs 48 y) yet markedly sicker: ventricular-assist device 8.1 % vs 3.8 %, extracorporeal membrane oxygenation 2.7 % vs 0 %, prior sternotomy 60 % vs 36 % (all P &lt; 0.05). Procurement distance quadrupled (198 vs 51 nm) and cold-ischemic time lengthened (3.7 vs 3.0 h; P &lt; 0.001). Kaplan–Meier curves (Image 2) showed higher Modern-era mortality for the full cohort at 90 days (13.5 % vs 6.2 %) and 1 year (17.5 % vs 12.1 %; both P ≤ 0.007); ACHD-only curves revealed an even wider Modern-era deficit at 90 days (P = 0.003) and 1 year (P = 0.007). Each additional ischemic hour increased 1-year hazard 22 % (HR 1.22, P = 0.007). The Modern era × ACHD term was strong (HR 3.9, P = 0.009), indicating nearly four-fold excess risk for Modern-era ACHD recipients. Conditional curves equalised beyond day 30 (P = 0.36) ( Image 3). Deaths shifted toward cerebrovascular events (15 % vs 3 %), organ failure (23% vs 15% and primary graft failure (11 % vs 3 %) Conclusions: Survival has declined in the Modern era for CHLT overall and—most strikingly—for ACHD recipients, likely driven by greater physiologic and surgical complexity and longer cold ischemia. Because deaths cluster within the peri-operative window, earlier ACHD referral, cold-ischemia reduction, and ACHD-focused peri-operative pathways are essential. Allocation policies that broadened sharing expanded access but now require refinement to safeguard this vulnerable ACHD CHLT population.