Future care for long-term cancer survivors: towards a new model

PurposeThe increase in the prevalence "long-term cancer survivor” (LCS) patients is expected to increase the cost of LCS care. The aim of this study was to obtain information that would allow to optimise the current model of health management in Spain to adapt it to one of efficient LCS patient care.MethodsThis qualitative study was carried out using Delphi methodology. An advisory committee defined the criteria for participation, select the panel of experts, prepare the questionnaire, interpret the results and draft the final report.Results232 people took part in the study (48 oncologists). Absolute consensus was reached in three of the proposed sections: oncological epidemiology, training of health professionals and ICT functions.ConclusionThe role of primary care in the clinical management of LCS patients needs to be upgraded, coordination with the oncologist and hospital care is essential. The funding model needs to be adapted to determine the funding conditions for new drugs and technologies.

Future care for long-term cancer survivors: towards a new model.

PURPOSE: The increase in the prevalence "long-term cancer survivor" (LCS) patients is expected to increase the cost of LCS care. The aim of this study was to obtain information that would allow to optimise the current model of health management in Spain to adapt it to one of efficient LCS patient care. METHODS: This qualitative study was carried out using Delphi methodology. An advisory committee defined the criteria for participation, select the panel of experts, prepare the questionnaire, interpret the results and draft the final report. RESULTS: 232 people took part in the study (48 oncologists). Absolute consensus was reached in three of the proposed sections: oncological epidemiology, training of health professionals and ICT functions. CONCLUSION: The role of primary care in the clinical management of LCS patients needs to be upgraded, coordination with the oncologist and hospital care is essential. The funding model needs to be adapted to determine the funding conditions for new drugs and technologies.

Vaginal neutrophils eliminate sperm by trogocytosis.

STUDY QUESTION: What is the vaginal polymorphonuclear (PMN) spermicidal mechanism to reduce the excess of sperm? SUMMARY ANSWER: We show that PMNs are very efficient at killing sperm by a trogocytosis-dependent spermicidal activity independent of neutrophil extracellular traps (NETs). WHAT IS KNOWN ALREADY: Trogocytosis has been described as an active membrane exchange between immune cells with a regulatory purpose. Recently, trogocytosis has been reported as a mechanism which PMNs use to kill tumour cells or Trichomonas vaginalis. STUDY DESIGN, SIZE, DURATION: We used in vivo murine models and human ex vivo sperm and PMNs to investigate the early PMN-sperm response. PARTICIPANTS/MATERIALS, SETTING, METHODS: We set up a live/dead sperm detection system in the presence of PMNs to investigate in vivo and ex vivo PMN-spermicidal activity by confocal microscopy, flow cytometry and computer-assisted sperm analysis (SCA). MAIN RESULTS AND THE ROLE OF CHANCE: We revealed that PMNs are highly efficient at killing sperm by way of a NETs-independent, contact-dependent and serine proteases-dependent engulfment mechanism. PMNs 'bite' sperm and quickly reduce sperm motility (within 5 min) and viability (within 20 min) after contact. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was conducted using murine models and healthy human blood PMNs; whether it is relevant to human vaginal PMNs or to cases of infertility is unknown. WIDER IMPLICATIONS OF THE FINDINGS: Vaginal PMNs attack and immobilize excess sperm in the vagina by trogocytosis because sperm are exogenous and may carry pathogens. Furthermore, this mechanism of sperm regulation has low mucosal impact and avoids an exacerbated inflammatory response that could lead to mucosal damage or infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was partially supported by Ministry of Economy and Competitiveness ISCIII-FIS grants, PI16/00050, and PI19/00078, co-financed by ERDF (FEDER) Funds from the European Commission, 'A way of making Europe' and IiSGM intramural grant II-PI-MRC-2017. M.R. holds a Miguel Servet II contract (CPII14/00009). M.C.L. holds IiSGM intramural contract. There are no competing interests.

Epidemiology of diverticular disease -- systematic review of the literature.

INTRODUCTION: Associated with the Western diet and life style,diverticular disease is affecting more and more developing countries worldwide. Recent studies show an increase in incidence of the disease at young age, that raises the risk of complications, along with major consequences for the patient but also for the healthcare system. METHOD: Systematic review of the literature with US National Library of Medicine and National Institutes of Health International PubMed Medline, using abstracts and articles available in PubMed Medline, Cochrane databases searching for ("Diverticulosis, Colonic epidemiology" [MeSH] OR"Diverticulosis, Colonic etiology" [MeSH] OR "Diverticulosis,Colonic genetics" [MeSH] OR "Diverticulosis, Colonic history" [MeSH]). RESULTS: Even from the rise of diverticular disease as a public healthcare problem, at the end of the previous century, it was associated with a diet rich in refined sugars, lacking vegetable fibres. The higher incidence in countries like U.S.A., Canada, United Kingdom and the northern states compared with its rare occurrence in the sub-Saharan African continent, strengthen the anterior assumptions. In regions like Asia, the disease pattern is characterized by are latively low incidence of colonic diverticular disease, with distribution of diverticula mainly on the right colon. The different incidence by sex and age show the possible existence of hormonal protective factors. Studies from countries with a rich ethnic diversity, bring into question the probable genetic predisposition to diverticular disease, fact backed-up by the few studies on twins and 1st degree relatives available in the literature. DISCUSSION: The rising incidence of colonic diverticular disease in Romania makes our country adhere the epidemiologic model existing in countries with a close socio-economic status.Although with a lower incidence than countries that have adopted a Western diet, Romania is likely to encounter a public health problem, if certain measures to identify and minimise the population exposure to risk factors are not taken.

Trauma registry -- a necessity of modern clinical practice.

INTRODUCTION: Traumas represent the cause of 10 % of deaths in the entire world. The successful development of trauma systems, including the use of trauma registries, played a significant part in lowering the mortality and the disabilities due to injuries resulted from trauma. METHOD: Review of the literature using computerized database of National Library of Medicine and the International Institutes of Health MEDLINE using PubMed interface. There were selected the articles that address the issue of trauma registry from the different world trauma systems. RESULTS: Trauma registries have developed once they were introduced in centers and trauma systems in the United States of America in 1970. First trauma database processed on computers was created in 1969 in Cook County Hospital in Chicago. This database became the prototype of trauma registry in Illinois which started gathering information from 50 designated hospitals across the entire state in 1971.Countries with limited resources were able to start useful trauma registers. Continuous financing and dedicated personnel inside the team are two essential factors in the success of a trauma registry. NISS (New Injury Severity Score) higher than 15 is a widely used inclusion criteria in the trauma register. Exclusion is represented by patients admitted at over 24 hours after the accident, those declared dead before hospital arrival or with no signs of life on arrival in hospital. In addition, it is recommended that asphyxia,drowning and burns to be excluded. CONCLUSION: The improvements regarding the treatment of multi-traumatized people in developing countries depend on establishing and performance of trauma systems, where trauma registry represents a part of these systems infrastructure.

Survey of CMV management in pediatric allogeneic HSCT programs, on behalf of the inborn errors, infectious diseases and pediatric diseases working parties of EBMT.

Human CMV infection is a frequent complication after HSC in children with remarkable morbidity and mortality. Antiviral drugs are relatively efficient but have numerous side effects. They are used as prophylactic, pre-emptive or therapeutic medicines. It is still a matter of debate which option is the best strategy. No uniform procedure has emerged regarding these three options, and new immunologic tools have raised more questions for physicians. To assess the current practice in the management of CMV infection, we sent a questionnaire to the EBMT centers performing hematopoietic SCT (HSCT) in children. Fifty-six out of 196 responded to the questionnaire (28.5%). Quantitative PCR was the most common monitoring tool (44/56). Only 4/56 centers use the pp65 antigenemia alone. All centers used pre-emptive strategy (56/56). 21/56 centers also used prophylactic measures, 13/21 after analysis of donor/receptor serologic status. Ganciclovir was the most common first-line agent for CMV disease (55/56). The most common dose and duration for induction treatment were 5 mg/kg bid (47/55) for 14 days (20/55). There is no uniform procedure for researching resistance strain, antiviral second-line therapy or cell therapy. A harmonization process should enable sound prospective trials to improve prevention, control and cure of CMV disease in children and adolescents.

Current strategies in the therapeutic approach for adenocarcinoma of the ampulla of Vater.

INTRODUCTION: Ampulla of Vater tumors, neoplastic diseases located at the confluence of the common bile duct with the main pancreatic duct; represent 0.2% of all gastrointestinal cancers. METHOD: Retrospective study of all patients admitted in the Emergency Hospital of Bucharest Romania between January 2008 and January 2013, the only selection criterion used being a pathology report which describes an ampulla of Vater carcinoma. We have also performed a review of the medical literature up to 2013, using the PubMed/Medline, Proquest Hospital Collection, Science Direct, Cochrane Library and Web of Science databases. We have used different combinations of the following keywords: "ampulla of Vater", "carcinoma", "resection", reviewing the reference list of retrieved articles for further relevant studies. RESULTS: Forty eight patients with ampulla of Vater carcinoma were identified, of whom 59.6% men, 71% from urban areas, and a mean age of 66 ± 13.3 years. Most patients were admitted for obstructive jaundice (49%), right upper quadrant abdominal pain (19%), nausea and loss of appetite in 13%, loss of weight (13%) and upper digestive obstruction in 6% of cases. All patients were evaluated with abdominal transparietal ultrasonography and double contrast, pancreatic protocol, Mutidetector Row Computed Tomography. The abdominal Magnetic Resonance Imaging was performed in 10 cases, upper gastrointestinal endoscopy in 9 cases, and Endoscopic Retrograde Cholangiopancreatography in 39 cases. According to the AJCC Cancer Staging 9% were into stage I, 47% into stage II, 40% into stage III and 4% into stage IV of the disease. The therapeutic approach was surgical for 44 patients and an endoscopic palliation with stent insertion in 4 cases. The surgical procedure was represented by Whipple pancreatoduodenectomy in 27 cases, pylorus preserving pancreatoduodenectomy in 15 cases and exploratory laparotomy in 2 cases. Early morbidity was represented by pancreatic leakage in 4 cases. CONCLUSIONS: There are clinical scenarios in which it is quite challenging to distinguish a primary ampullary adenocarcinoma based on a preoperative workup. Nevertheless, an aggressive approach should be performed, knowing the higher resectability rates and a five-year survival for these patients. Complete surgical resection should be performed in all medically fit patients, candidates for pancreatoduodenectomy, by a high volume, trained surgeon, able to offer a low morbidity and mortality.

Prehospital trauma care: a clinical review.

INTRODUCTION: There are many controversies related to the trauma patient care during the pre-hospital period nowadays. Due to the heterogeneity of the rescue personnel and variability of protocols used in various countries, the benefit of the prehospital advanced life support on morbidity and mortality has been not established. METHOD: Systematic review of the literature using computer search of the Library of Medicine and the National Institutes of Health International PubMed Medline database using Entre interface.We reviewed the literature in what concerns the basic and advanced life support given to the trauma patients during the prehospital period. RESULTS: Although the organization of the medical emergency system varies from a country to another, the level of patient'scare can be classified into two main categories: Basic Life Support (BLS) and Advanced Life Support (ALS).There are many studies addressing what to be done at the scene.The prehospital care can be divided into two extremes: stay and play/treat then transfer or scoop and run/load and go. CONCLUSIONS: A balance between "scoop and run" and "stay and play" is probably the best approach for trauma patients. The chosen approach should be made according to the mechanism of injury (blunt versus penetrating trauma), distance to the trauma center (urban versus rural) and the available resources.

[Trauma scores: a review of the literature]. / Scorurile traumatice: revizie a literaturii.

BACKGROUND: A quantitative method for measuring trauma severity has many potential applications: patient triage, a common terminology about injuries severity, prognosis assessment, trauma care audit and epidemiological. METHOD: Systematic review of the literature using computer searching of Library of Medicine and the National Institutes of Health International MEDLINE database using PubMed Entre interface. We have selected articles about the main scoring systems used in today's trauma care. RESULTS: Trauma scores were introduced more than 30 years ago, for assigning numerical values to anatomical lesions and physiological changes after an injury. Physiologic Scores describe changes due to a trauma and translated by changes in vital signs and consciousness. Anatomical Scores describe all the injuries recorded by clinical examination, imaging, surgery or autopsy. If physiological scores are used at first contact with the patient (for triage) and then repeated to monitor patient progress, anatomic scores are used after the diagnosis is complete, generally after patient discharge or postmortem. They are used to stratify trauma patients and to measure lesion severity. Scores that include both anatomical and physiological criteria (mixed scores) are useful for patient prognosis. CONCLUSIONS: Despite their imperfections, trauma scores are very important tools in trauma patients management and research. Using large national databases allow a better research, validation and development of scoring systems.

The EBMT activity survey: 1990-2010.

A total of 654 centers from 48 countries were contacted for the 2010 survey. In all, 634 centers reported a total of 33 362 hematopoietic SCT (HSCT) with 30 012 patients receiving their first transplant (12 276 allogeneic (41%) and 17 736 autologous (59%)). Main indications were leukemias: 9355 (31%; 93% allogeneic), lymphoid neoplasias specifically Non Hodgkin's lymphoma, Hodgkin's lymphoma and plasma cell disorders: 17 362 (58%; 12% allogeneic), solid tumors: 1585 (5%; 6% allogeneic) and non-malignant disorders: 1609 (6%; 88% allogeneic). There were more unrelated donors than HLA-identical sibling donors (53% versus 41%); the proportion of peripheral blood as stem cell source was 99% for autologous and 71% for allogeneic HSCT. Cord blood was primarily used in allogeneic transplants (6% of total) with three autologous cord blood HSCT being reported. The number of transplants has increased by 19% since 2005 (allogeneic 37% and autologous 9%) and continued to increase by about 1100 HSCT per year since 2000. Patterns of increase were distinct and different. The data show the development of transplantation in Europe since 1990, with the number of patients receiving a HSCT increasing from 4200 to over 30 000 annually. The most impressive trend seen is the steady increase of unrelated donor transplantation, in parallel to the availability of unrelated donors through donor registries.

[Mechanism of injury--trauma kinetics. What happend? How?]. / Mecanismul lezional--cinetica in trauma. Ce s-a intâmplat? Cum?

INTRODUCTION: Understanding the mechanism of injuries represents a key element in blunt and penetrating trauma management. METHOD: Systematic review of the main types of the modem trauma mechanisms, using Medline, Cochrane Library and Embase databases. RESULTS: To properly understand the road car accident injuries, trauma surgeon should know as many details from the scene: the speed of cars, impact direction, if the car rolled over, if occupants were restrained, if airbags exploded, vehicle telemetry, extrication time. Motorcyclists are 20 to 30 times more at risk for severe injuries or death than the four-wheel vehicle occupants. Current evidence shows a significant decrease in injuries severity by increasing use of seat-belts, motorcycle helmets, childrestrains and speed limit. Despite this, few countries around the world have road safety laws relating to key factors that can be considered sufficiently comprehensive in scope. Many modern trauma systems use for prehospital triage mechanism of injury criteria. CONCLUSIONS: The trauma surgeon should know the mechanism of injury. This allows a high suspicion for potential injuries, their early diagnosis and increased quality in the care of trauma patients.

[History of trauma care]. / Istoria îngrijirii pacientului traumatizat.

BACKGROUND: Since its inception, the man suffered injuries through falls, fire, drowning and interpersonal conflict. While the mechanism and frequency of different specific injuries has changed passing of millennia, trauma remains an important cause of mortality and morbidity in modern society. Although the war is presented as one of the four knights of the Apocalypse, we must emphasize the important developments of surgical experience during war. The purpose of this study is to highlight the lessons learned during the history and how they changed the modern trauma care. METHOD: Systematic review of English language literature using computer searching of Library of Medicine and the National Institutes of Health International MEDLINE database using PubMed Entre interface. RESULTS: The first historical record of a trauma medical care is 3605 years ago. Over the past decades, one of the most important changes in trauma patient care is the selective nonoperative management (SNOM) of significant abdominal visceral injuries. SNOM was first described in 1968, for splenic trauma, by Upadhyay and Simpson. It was accepted much later for liver injuries. Beginning from 1960 - 1970, SNOM was introduced for abdominal stab wounds. Exploratory laparotomy remains the standard approach for abdominal gunshot wounds until 1990, when centers from United States and South Africa first reported cases successfully managed nonoperatively. CONCLUSIONS: The trauma surgery has evolved continuously over the centuries, according to more and more severe modem injuries.

[Trauma--epidemiology: where are we today?]. / Epidemiologia traumatismelor--unde ne aflam astazi?

INTRODUCTION: Understanding the epidemiological data on injuries is the cornerstone of modern interventions targeting prevention and treatment to decrease their mortality and morbidity. METHOD: Systematic review of English literature using computer searching and selecting articles that describe the epidemiological data for the main causes of nowadays trauma. RESULTS: Trauma meets the conditions of a pandemy, 5.8 million people dying evey year and 8.4 million being expected in 2020. Trauma is one of the main five causes of mortality and morbidity for all age groups below 60 years. Most deaths caused by road car accidents occur in young adults aged 15-44 years. Over half of deaths by drowning occur between 0-14 years. Over 40% of mortality by falls occurs in people over 70 years. 60% of deaths by poisoning occurs in people 15-59 years. Over 60% of human aggression mortality occurs in young adults aged 15-44 years. Suicide occurs most often in people between 15-44 years. Alcohol consumption is closely correlated with mortality and morbidity due to trauma. CONCLUSIONS: Modem trauma system management should always consider that trauma mortality is the number most easily to measure and to reporte, but it represent only the tip of the iceberg.

Agrupación estacional de tres casos de síndrome de Löfgren / No disponible

El síndrome de Löfgren es una entidad definida por lapresencia de eritema nudoso, adenopatías hiliares bilaterales,poliartralgias, fiebre y, ocasionalmente, iritis. Se trata deuna forma habitual de presentación aguda de la sarcoidosis,enfermedad sistémica de etiología desconocida caracterizadapor la presencia de granulomas no caseificantes en los órganosafectados. Clásicamente se ha descrito su apariciónpreferente en primavera e invierno. Aunque para el diagnósticode sarcoidosis se requiere, además de un cuadro clínicoy una evolución compatibles, la presencia de granulomas nocaseificantes en uno o más de los órganos afectos, y la exclusiónde otras enfermedades granulomatosas, infecciosas ono, para el síndrome de Löfgren se acepta el diagnóstico sinconfirmación histológica, habida cuenta de su buen pronósticoy su presentación clínica peculiar.Presentamos tres casos de síndrome de Löfgren de aparicióncoincidente en el tiempo, y con buena evolución sintratamiento específico, a pesar de que una de las pacientesmostraba una afectación leve de la función pulmonar conafectación radiológica pulmonar (AU)

Löfgren’s syndrome is characterized by the presence oferythema nodosum, bilateral hilar adenopathy, polyarthralgias,fever and, occasionally, iritis. It is usually an acute formof sarcoidosis, which is a systemic disease of unknown etiology,characterized by the presence of non-caseificant granulomatasin the affected organs. It classically appears inspring and winter. The presence of non-caseificant granulomatason one or more of the affected organs, and the exclusionof any other granulomatous diseases (infectious or not)is necessary to diagnose sarcoidosis in addition to a compatibleclinical picture and course, However, in regards toLöfgren’s syndrome, the diagnosis can be accepted withouthistological confirmation because of its good prognosis andits characteristic clinical presentation.We present three cases of Löfgren’s syndrome which hadappeared at the same time and with good progress withoutspecific treatment even though one of the patients had aslight impairment of the pulmonary function with pulmonaryradiological involvement (AU)

[Prostatic malacoplakia: report of a case and review of the literature]. / Malacoplaquia de próstata: aparición de un caso y revisión de la literatura.

OBJECTIVE: To describe an additional case of malakoplakia of the prostate. The etiopathogenesis, the histological and clinical features of this disease are analyzed and the literature briefly reviewed. METHODS/RESULTS: The pathological features of malakoplakia of the prostate in an elderly man with severe prostatic syndrome and recurrent urinary infections from E. Coli are described. The clinical manifestations disappeared following adenomectomy according to the Millin technique. CONCLUSION: Diagnosis of malakoplakia of the prostate is based on the pathological findings. The importance of the pathologist's role in the diagnosis of this condition, which will determine the treatment to follow, is therefore underscored.

[Acute abdomen secondary to pyonephrosis. Perinephritic abscess with fistula to peritoneal cavity]. / Abdomen agudo secundario a pionefrosis. Absceso perinefrítico, fistulizado a cavidad peritoneal.

OBJECTIVE: To describe a case of acute abdomen arising from an underlying urological condition. METHODS/RESULTS: Herein we describe a patient with acute abdomen arising from a pyonephrotic kidney with fistulization to the peritoneal cavity. The clinical manifestations disappeared following nephrectomy by the anterior approach and drainage of the intraperitoneal cavity. CONCLUSION: Although infrequent, it should be taken into account that peritoneal abscess and/or pyonephrosis can cause acute abdomen when they fistulize to the peritoneal cavity.

[Erectile dysfunction caused by neurapraxia of the pudendal nerve after the use of a traction table for the treatment of traumatic fractures. Report of a case and review of the literature]. / Disfunción eréctil por neuroapraxia del nervio pudendo tras el uso de la mesa de tracción para la solución de fracturas traumatológicas. A propósito de un caso y revisión de la literatura.

OBJECTIVE: To describe a case of erectile dysfunction as a result of traction on the fracture table. METHODS: We report on a 39-year-old man who developed erctile dysfunction postoperatively and for several months thereafter, following intramedullary nailing with the Grosse-Kept bolt type fixation system. RESULTS: The patient spontaneously recovered erectile function six months after orthopaedic treatment. CONCLUSION: Erectile dysfunction induced by orthopaedic fracture table is a complication that should be taken into account. There are many procedures available to reduce the risk of this complication.

[Acute orchiepididymitis: assessment with high-resolution ultrasonography in 52 cases]. / Orquiepididimitis aguda: valoración mediante ecografía de alta resolución en 52 casos.

OBJECTIVES: The present study describes our experience in ultrasound diagnosis of acute orchiepididymitis, with special reference to the most common US patterns and complications of this disease entity. METHODS: In acute scrotum suspected as having an inflammatory origin, high resolution ultrasonography is performed in the acute phase in addition to routine blood and urine analyses. Treatment and subsequent US control evaluation vary according to each case. RESULTS: The sonographic findings in 52 cases with a clinical suspicion of acute orchiepididymitis are presented. All examinations were performed in the acute phase. Subsequent sonographic control evaluation was performed 2-4 months after treatment. Seven cases had a negative ultrasound; in 4 cases ultrasound disclosed a different pathology (2 tumors, 1 testicular torsion and 1 hydatid torsion); 12 had both testicular and epididymal involvement; one had testicular and 28 had epididymal involvement alone. Complications were observed in 21 cases (hydrocele, abscess, pyocele, infarct...). Sonographic evaluation after treatment showed complete resolution in 26 cases whereas 15 cases showed postinflammatory sequelae (atrophy, changes in testicular ultrasound pattern, calcifications, chronic hydrocele...). The ultrasound findings indicated surgery in 2 cases. CONCLUSIONS: High resolution ultrasonography is currently the diagnostic method of choice in scrotal inflammation. It permits determining the extent of the lesion (orchitis, epididymitis, orchiepididymitis), complications (hydrocele, hematocele, pyocele, abscess, infarct...) and the result of therapy.

Bone marrow gene transfer in three patients with adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency results in severe combined immune deficiency disease (SCID), which is fatal without treatment. Allogeneic bone marrow transplantation (BMT) is the treatment of choice if an HLA-identical sibling bone marrow donor is available, resulting in almost 100% cure rate. BMT-related mortality is high in patients lacking such a donor. For these patients, efficient transfer of a recombinant ADA gene into hematopoietic stem cells is a therapeutic option if it results in the outgrowth of a 'genetically repaired' lymphoid system. Based on successful gene transfer studies in monkeys, we performed retrovirus-mediated gene transfer into CD34+ bone marrow cells of three patients with ADA deficiency. Two patients received bovine ADA conjugated to polyethylene glycol (PEG-ADA); in the third patient, PEG-ADA was started 4 months after gene transfer. Gene transfer resulted in a 5-12% transduction frequency of in vitro colony forming cells (CFU-Cs). No toxicity was observed during and after infusion of the graft. Following infusion of the transduced CD34+ cells, transduced granulocytes and mononuclear cells persisted in the circulation for 3 months. In addition, the gene was present in the marrow of one of the patients at 6 months after gene transfer. Expression of the gene was not detected. After this period, the gene could not be detected. In monkey studies we showed that myeloablation, which was not performed in the patients, may enhance engraftment of genetically modified cells. We hypothesize that lack of myeloablation, administration of bovine ADA and low numbers of transduced progenitor cells all may have contributed to the relative low numbers of transduced cells in the patients. Under these conditions, no selective advantage of the genetically corrected progenitor cells was observed.