Treating Anemia in the Preanesthesia Assessment Clinic: Results of a Retrospective Evaluation.

BACKGROUND: Perioperative anemia is challenging during hospital stay because anemia and red blood cell (RBC) transfusions are associated with an increased morbidity and mortality. With the implementation of patient blood management (PBM), a preanesthesia assessment clinic to screen and treat anemia before elective surgery was institutionalized at Muenster University Hospital, Germany. The main objective of this study was to evaluate the association between treating preoperative anemic patients with intravenous iron (IVI) and (primarily) presurgical hemoglobin levels and (secondarily) use of RBCs and mortality. METHODS: Between April 1, 2014, and July 4, 2016, patients scheduled for elective surgery with a risk for RBC transfusions >10% in 2013 were screened for preoperative anemia and, if indicated, treated with IVI. Patients' data, time span between visit in the anesthesia/PBM clinic and surgery, demographic data, type of surgery, the difference of hemoglobin levels between visit and surgery, RBC transfusion, infectious-related International Classification of Disease codes during hospital stay, and 1-year survival were determined retrospectively by screening electronic data files. In addition, patients were interviewed about adverse events, health-related events, and infections via telephone 30, 90, and 365 days after visiting the anesthesia/PBM clinic. RESULTS: A total of 1101 patients were seen in the anesthesia/PBM clinic between days -28 and -1 (median [Q1-Q3], -3 days [-1, -9 days]) before elective surgery. Approximately 29% of patients presented with anemia, 46.8% of these anemic patients were treated with ferric carboxymaltose (500-1000 mg).In the primary analysis, hemoglobin levels at median were associated with a reduction between the visit in the anesthesia/PBM clinic and the surgery in all nonanemic patients on beginning of medical treatment (nonanemic patients at median -2.8 g/dL [-4, -0.9 g/dL], while anemic patients without IVI presented with median differences of -0.8 g/dL [-2, 0 g/dL] and anemic patients with IVI of 0 g/dL [-1.0, 0.5 g/dL]). Hemoglobin levels raised best at substitution 22-28 days before surgery (0.95 g/dL [-0.35, 1.18 g/dL]). Due to the selection criteria, transfusion rates were high in the cohort. Overall, there was no association between IVI treatment and the use of RBC transfusions (odds ratio for use of RBCs in anemic patients, no IVI versus IVI: 1.14; 95% confidence interval, 0.72-1.82). Patients treated with or without IVI presented a comparable range of International Classification of Disease codes related to infections. Telephone interviews indicated similar adverse events, health-related events, and infections. Cox regression analysis showed an association between anemia and reduced survival, regardless of IVI. CONCLUSIONS: An anemia clinic within the preanesthesia assessment clinic is a feasible and effective approach to treat preoperative anemia. The IVI supplementation was safe but was associated with decreased RBC transfusions in gynecology/obstetric patients only. The conclusions from this retrospective analysis have to be tested in prospective, controlled trials.

Medical Liability and Patient Law in Germany: Main Features with Particular Focus on Treatments in the Field of Interventional Radiology.

UNLABELLED: On February 26th, 2013 the patient law became effective in Germany. Goal of the lawmakers was a most authoritative case law for liability of malpractice and to improve enforcement of the rights of the patients. The following article contains several examples detailing legal situation. By no means should these discourage those persons who treat patients. Rather should they be sensitized to to various aspects of this increasingly important field of law. To identify relevant sources according to judicial standard research was conducted including first- and second selection. Goal was the identification of jurisdiction, literature and other various analyses that all deal with liability of malpractice and patient law within the field of Interventional Radiology--with particular focus on transarterial chemoembolization of the liver and related procedures. In summary, 89 different sources were included and analyzed. The individual who treats a patient is liable for an error in treatment if it causes injury to life, the body or the patient's health. Independent of the error in treatment the individual providing medical care is liable for mistakes made in the context of obtaining informed consent. Prerequisite is the presence of an error made when obtaining informed consent and its causality for the patient's consent for the treatment. Without an effective consent the treatment is considered illegal whether it was free of treatment error or not. The new patient law does not cause material change of the German liablity of malpractice law. KEY POINTS: •On February 26th, 2013 the new patient law came into effect. Materially, there was no fundamental remodeling of the German liability for medical malpractice. •Regarding a physician's liability for medical malpractice two different elements of an offence come into consideration: for one the liability for malpractice and, in turn, liability for errors made during medical consultation in the process of obtaining informed consent. •Forensic practice shows that patients frequently enforce both offences concurrently.

Retrospective Analysis of the Blood Component Utilization in a University Hospital of Maximum Medical Care.

BACKGROUND: Demographic data illustrate clearly that people in highly developed countries get older, and the elderly need more blood transfusions than younger patients. Additionally, special extensive therapies result in an increased consumption of blood components. Beyond that the aging of the population reduces the total number of preferably young and healthy blood donors. Therefore, Patient Blood Management will become more and more important in order to secure an increasing blood supply under fair-minded conditions. METHODS: At the University Hospital of Münster (UKM) a comprehensive retrospective analysis of the utilization of all conventional blood components was performed including all medical and surgical disciplines. In parallel, a new medical reporting system was installed to provide a monthly analysis of the transfusional treatments in the whole infirmary, in every department, and in special blood-consuming cases of interest, as well. RESULTS: The study refers to all UKM in-patient cases from 2009 to 2011. It clearly demonstrates that older patients (>60 years, 35.2-35.7% of all cases, but 49.4-52.6% of all cases with red blood cell (RBC) transfusions, 36.4-41. 6% of all cases with platelet (PTL, apheresis only) transfusions, 45.2-48.0% of all cases with fresh frozen plasma (FFP) transfusions) need more blood products than younger patients. Male patients (54.4-63.9% of all cases with transfusions) are more susceptible to blood transfusions than female patients (36.1-45.6% of all cases with transfusions). Most blood components are used in cardiac, visceral, and orthopedic surgery (49.3-55.9% of all RBC units, 45.8-61.0% of all FFP units). When regarding medical disciplines, most transfusions are administered to hematologic and oncologic patients (12.9-17.7% of all RBC units, 9.2-12.0% of all FFP units). The consumption of PTL in this special patient cohort (40.6-50.9% of all PTL units) is more pronounced than in all other surgical or in non-surgical disciplines. CONCLUSION: The results obtained from our retrospective analysis may help to further optimize the responsible and medical indication-related utilization of blood transfusions as well as the recruitment of blood donors and their timing. It may be also a helpful tool in order to avoid needless transfusions and transfusionassociated adverse events.

Thermogravimetry coupled to single photon ionization quadrupole mass spectrometry: a tool to investigate the chemical signature of thermal decomposition of polymeric materials.

Mass spectrometry (MS) is an established analytical technique to analyze evolved gas in thermogravimetry (TG). In this study, for the first time a novel SPI-MS technique using an electron beam pumped VUV excimer lamp as photon source (lambda = 126 nm) was employed in conjunction with thermogravimetry. The coupling was achieved with an improved heated interface and adjacent transfer capillary between TG and ion source of a quadrupole mass spectrometer. The feasibility of this approach was proven by investigating semivolatile substances such as long-chain alkanes (heptadecane C17H36), polymers, e.g., polystyrene, polycarbonate, and acrylonitrile-butadiene-styrene, polymer mixtures and blends. Mass spectra with almost no fragmentation were obtained, and quantification of selected substances could be achieved. Polymer mixtures could be distinguished by their SPI mass spectra, and the effect of premixing of polymers has been accessed. Its unique attributes render the TA-SPI-MS method a promising new tool for quantitative and qualitative evaluation of complex organic thermal degradation products.

Effect of topical oral G-CSF on oral mucositis: a randomised placebo-controlled trial.

Oral mucositis is a dose-limiting toxicity of intensive chemotherapy. It is caused directly by the cytotoxic effect of chemotherapeutic agents and indirectly by sustained neutropenia. Severe oral mucositis is an important predisposing factor for life-threatening septic complications during aplasia. It also reduces quality of life. At present, no effective causal prophylaxis or treatment against oral mucositis is established. We performed a prospective randomised placebo-controlled trial using topical oral r-metHuG-CSF (filgrastim) in high-grade lymphoma patients treated according to the B-NHL protocol, which contains high-dose methotrexate and causes severe oral mucositis (WHO grades I-IV) in >50% of patients. Between August 1996 and July 1997, a total of 32 chemotherapy cycles were documented in eight patients (four male, four female). Mucosal erythema and ulceration were recorded. All patients assessed their oral pain and impact on swallowing daily, using a subjective scale from no to maximal discomfort (1-10). In addition, oral mucositis was assessed according to the WHO score. Filgrastim was administered in 16 cycles as a viscous mouthrinse (carboxymethylcellulose 2%, oleum citrii) 4 x 120 microg/day from days 10 to 16. Sixteen cycles were given to control patients, of these 14 with placebo, and another two cycles with no treatment. Severe mucositis (WHO grade III/IV) was documented in 21 of 32 cycles (65.5%). A difference of borderline significance was observed for the reduction of maximum severity of oral mucositis between G-CSF vs placebo (P = 0.058), with a reduction of WHO grade IV of 50% (four G-CSF vs eight control). The number of days in hospital was reduced significantly in the G-CSF group (P = 0.02). In conclusion, topical oral G-CSF mouthrinses may be beneficial to reduce oral mucositis.

Early detection of chronic disseminated Candida infection in leukemia patients with febrile neutropenia: value of computer-assisted serial ultrasound documentation.

Computer tomography (CT) is known to be as sensitive as magnetic resonance imaging (MRI) in detecting fungal microabscesses in chronic disseminated candidiasis. However, all imaging techniques have to be repeated in cases of suspected fungal infection. Therefore, use of the CT or MRI scan is limited. Only ultrasound (US) examinations can be repeated as often as needed. The disadvantage of US is a lack of sufficient documentation. We analyzed the value of computer-assisted documentation in serial ultrasonography of leukemia patients with suspected chronic disseminated candidiasis. From November 1996 until October 1997, a total of 220 ultrasound examinations (Kranzbühler Logiq 500, 3.5 MHz convex array) were performed in 58 patients undergoing intensive chemotherapy. Initial US pictures were stored on a personal computer and compared with the live US at the time of reevaluation in cases of persistent fever. Ultrasound detected microabscesses in liver and/or spleen in eight of the 58 patients. Diagnosis was confirmed by autopsy/biopsy (n = 6), blood culture (n = 1), and a significant Candida antibody titer (n = 1). Focal lesions occurred only after neutrophil recovery. However, a newly evolving nonhomogeneous, micronodular pattern of liver and spleen occurred during febrile neutropenia in three patients, and two of these developed focal lesions subsequently. Follow-up was easy, since US pictures could be compared directly with stored examinations on screen. We conclude that serial US is sensitive in detecting microabscesses in the liver or the spleen. Computer-assisted US documentation proved to be a helpful tool for detection as well as in the follow-up of patients with chronic disseminated candidiasis.

[Possibilities and limits of ambulatory supportive measures in oncology exemplified by antibiotic therapy of febrile neutropenia]. / Möglichkeiten und Grenzen ambulanter supportiver Massnahmen in der Onkologie am Beispiel der Antibiotikatherapie febriler Neutropenien.

Neutropenia is common after intensive chemotherapy. Hospitalization and intravenous broad-spectrum antibiotics are the standard of care for febrile neutropenic patients because of the risk of serious complications and associated mortality. Short neutropenic periods (< 7 days) are considered to be at a low-risk in cases when fever occurs in clinically stable patients. Recent work suggests that such a low-risk population of febrile neutropenic patients might benefit from alternatives to inpatient care. The agents that best qualify for outpatient treatment include quinolones i.v./p.o., glycopeptides, ceftriaxone and aminoglycosides, particularly if the latter are given once daily. Response rates to antimicrobial therapy range from 80 to 95% in low-risk febrile neutropenia episodes. Treating these patients in an outpatient setting avoids hospitalization in 75 to 95%. There is no doubt that outpatient therapy may have several advantages, including lower costs and an improved quality of live. Outpatient antibiotic therapy for febrile low-risk neutropenia should be considered as an acceptable alternative to inpatient treatment.

Myelodysplastic syndromes: a guide to treatment with epoetin and colony-stimulating factors.

Myelodysplastic syndromes (MDS) are clonal disorders of haemopoietic stem cells which are characterised by peripheral cytopenia and, usually, by an increased bone marrow cellularity. Transfusions of red blood cells and platelets comprise the basis of supportive care for anaemia and thrombocytopenia. In patients who progress to acute myeloid leukaemia, cytotoxic chemotherapy is used. In MDS, haemopoietic growth factors can enhance: proliferation and differentiation of normal and myelodysplastic haemopoietic progenitor cells, and prevent premature apoptosisacceleration of haemopoietic recovery after intensive chemotherapy and amelioration of mature cell function; and sensitisation of malignant cells for the cytotoxic action of chemotherapeutic agents. There is widespread clinical experience with the use of epoetin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). A meta-analysis of 17 trials with EPO showed a stimulation of erythropoiesis, resulting in a discontinuation of the need for transfusions or an increase in haemoglobin levels of at least 15 g/L in 16% of 205 patients. Favourable factors for the response were an initial absence of a need for transfusion and a serum EPO level <200 U/L. In clinical phase I/II studies of GM-CSF administration, a dose-dependent increase in the absolute neutrophil count was seen in >80% of patients, as well as a decrease in the infection rate. The effect on survival could not be assessed. Lower platelet counts, with a risk of bleeding, bone pain, local erythema at the subcutaneous injection site and phlebitis during intravenous infusion, were observed. The combined administration of GM-CSF and EPO to a small number of patients resulted in an increase in haemoglobin levels or a decrease in the need for transfusion, with an overall response rate of 46%, but is not a proven treatment. The use of G-CSF increased the absolute neutrophil count in about 90% of patients with MDS, and was accompanied by an improvement of neutrophil function, which is frequently impaired in these patients. However, contradictory data exist on the influence of prophylactic G-CSF treatment on the infection rate. Bone pain and thrombocytopenia were the most important adverse effects of G-CSF treatment. Synergism of G-CSF and EPO has not yet been proven in randomised phase III trials, although selected patients showing no response to EPO alone may achieve normal haemoglobin levels after receiving additional G-CSF. Treatment in vivo with EPO, GM-CSF or G-CSF has not been shown to change the percentage of bone marrow cells carrying cytogenetic aberrations. However, individual patients have shown a reversal from a monoclonal to a polyclonal pattern with GM-CSF therapy.

Clinical use of hematopoietic growth factors in patients with myelodysplastic syndromes.

In myelodysplastic syndromes (MDS), pancytopenia and defective function of neutrophils and platelets lead to a high risk of infectious and hemorrhagic complications. The progression to acute myeloid leukemia adds to morbidity and mortality. Supportive care including red blood cell and platelet transfusions are still the cornerstone of therapeutic management. However, the clinical use of the recombinant hematopoietic growth factors has enlarged the range of therapeutic applications in patients with MDS. It is possible to reverse neutropenia in MDS patients by administration of G-CSF (granulocyte colony stimulating factor) or GM-CSF (granulocyte-monocyte colony stimulating factor). Because of the lower incidence of adverse events, G-CSF is preferable. However, neither G-CSF nor GM-CSF have been shown to reduce the rate of severe infection or mortality from infection when given prophylactically. In the case of a severe infection, therapeutic administration of G-CSF together with antibiotics might be justified in otherwise neutropenic MDS patients. Preliminary data suggest it to be possible to identify MDS patients with a higher than 50% chance of reversal of anemia or transfusion dependency by treatment with high-dose erythropoietin (EPO). Since patients with only slight impairment of erythropoiesis and no transfusion dependency have the highest response rates but need EPO the least, pharmacoeconomic analyses are urgently needed. Controlled randomized trials will have to ascertain whether combinations of EPO with G-CSF or GM-CSF are of benefit. Clinical studies with thrombopoietin (megakaryocyte growth and differentiation factor) have to be initiated to find out whether thrombocytopenia in MDS can be reversed.

G-CSF and cyclosporin induce an increase of normal cells in hypoplastic paroxysmal nocturnal hemoglobinuria.

Four paroxysmal nocturnal hemoglobinuria (PNH) patients with severe thrombocytopenia, hemolytic anemia and neutropenia were treated using a combination of filgrastim (G-CSF) and cyclosporin. In all patients a trilineage response of hematopoiesis was achieved. In addition, the proportion of glycosyl-phosphatidylinositol (GPI)-deficient granulocytes decreased. All patients mobilized CD34+ hematopoietic progenitors into peripheral blood after starting treatment with G-CSF. The majority of early progenitors (CD34+ CD38-) after mobilization into peripheral blood was found to be unaffected by the GPI-anchoring defect. No patient developed leukemia while under therapy. We conclude from these data that the combination of G-CSF and cyclosporin represents an efficient option for the treatment of hypoplastic PNH.

Acute abdomen due to endometriosis as a diagnostic and therapeutic challenge in the treatment of acute myelocytic leukemia.

Acute abdominal pain is a frequent diagnostic and therapeutic challenge in hematologic patients. We report on the very rare case of organ endometriosis with acute abdominal symptoms in a 43-year-old female patient with AML-M5, starting 4 days after induction chemotherapy with idarubicin, ara-C, and etoposide. The patient presented with an acute abdomen with clinical findings of acute cholecystitis, subileus, and local pain in the right upper abdomen accompanied by severe diarrhea. Probably due to impaired intestinal resorption, menstrual bleeding occurred despite regular administration of lynestrenol. Ultrasound examination of the abdomen disclosed a tumor with poor echoes in the pouch of Douglas, a subcapsular splenic hemorrhage, and a thickened gallbladder wall with surrounding edema. A cystic adnex tumor was confirmed by endovaginal ultrasound. Based on history and the findings on ultrasound, an endometriosis was diagnosed, and the LHRH agonist (nafarelin) was administered nasally in combination with lynestrenol. Following this medication the abdominal pain ceased, supporting the diagnosis of endometriosis. Nasal administration of an LHRH agonist in the following cycles of chemotherapy was effective in preventing further abdominal discomfort and vaginal bleeding. LHRH agonists should be given to patients with known endometriosis before starting myeloablative chemotherapy to prevent painful hemorrhage from endometriosis.

Immune thyroiditis after transplantation of allogeneic CD34+ selected peripheral blood cells.

A 28-year-old female patient underwent allogeneic PBSCT from her HLA-identical sister for AML in first CR. CD34+ cells were positively selected from PBPC using immunoaffinity columns. She received 8.0 x 10(6) CD34+ cells/kg and 1.74 x 10(6) CD3+ cells/kg body weight (BW). The patient developed acute GVHD III and mild limited chronic GVHD. Thirteen months after transplantation severe thyrotoxicosis requiring plasmapheresis occurred. Immune thyroiditis was confirmed cytologically by lymphocytic infiltration in a fine needle aspirate and by elevated thyroid-Ab-titers. The patient's donor had received thyroid hormone substitution for 10 years for hypothyroidism. The most probable cause of immune thyroiditis after allogeneic BMT is the transfer of antithyroid donor lymphocytes. These lymphocytes can also be transferred with a CD34+ selected peripheral stem cell graft. The transplantation of lymphocyte-depleted autologous bone marrow or PBPC grafts after myeloablative treatment is increasingly considered as potential treatment of severe autoimmune diseases. This case demonstrates that even low numbers of lymphocytes are capable of transferring autoimmune disorders.

Treatment with growth factors in myelodysplastic syndromes.

In myelodysplastic syndromes (MDS), pancytopenia leads to a high risk of infectious and hemorrhagic complications. The progression to acute myeloid leukemia adds to morbidity and mortality. While transfusions of red blood cells and platelets are still a cornerstone of the therapy, the clinical use of recombinant hematopoietic growth factors has enlarged the range of therapeutic applications in patients with MDS. It is possible to reverse neutropenia by administration of G-CSF (granulocyte colony stimulating factor) or GM-CSF (granulocyte-monocyte colony stimulating factor). In the case of a severe infection, therapeutic administration of G-CSF together with antibiotics might be justified in otherwise neutropenic MDS patients. Since especially patients with only slight impairment of erythropoiesis and no transfusion dependency have the highest response rates but need erythropoietin (EPO) the least, pharmacoeconomic analyses are urgently needed. Controlled randomized trials will have to ascertain wether combinations of EPO with G-CSF or GM-CSF are of benefit. Clinical studies with thrombopoietin (megakaryocyte growth and differentiation factor) have to be initiated to find out whether thrombocytopenia in MDS can be reversed.

Gamma delta-T cell-receptor-positive lymphocytes inhibit human hematopoietic progenitor cell growth in HIV type 1-infected patients.

In severe HIV infection, the majority of patients exhibit signs of hematopoietic deficiency including anemia, leukopenia, and thrombocytopenia. Besides other pathophysiological mechanisms, the disturbed helper/suppressor ratio of T-lymphocytes suggests that alterations within T cell subpopulations may have a suppressive effect on HIV-associated hematopoiesis. Since a delta TCS-1- and mostly CD-8-positive subpopulation of cytotoxic T-lymphocytes expressing the gamma delta-receptor is increased in peripheral blood and bone marrow of HIV-infected persons, it was the aim of this study to investigate the role of gamma delta-positive cells in HIV-associated bone marrow deficiency. The number of bone marrow-derived pluripotent colony-forming units (CFU-GEMM), burstforming units-erythrocyte (BFU-E), and colony-forming units-granulocyte-monocyte (CFU-GM) of HIV-1-positive patients was significantly (p < 0.05) increased after depletion of CD-8-positive, gamma delta-positive, and delta TCS-1-positive T-lymphocytes. In contrast, the depletion of these subpopulations had no stimulatory effect in healthy controls. Further experiments identified direct cellular contact between effector and hematopoietic progenitor cells and the production of interferon-gamma and tumor necrosis factor-alpha as the mechanisms mediating the suppressive effect of the delta TCS-1-positive cells in HIV-positive patients.

Modified antisense oligodeoxynucleotides against the splice acceptor site of tat do not inhibit in vitro hematopoietic colony growth in HIV-positive patients.

The hematopoietic failure in the majority of patients with progressive HIV infection is further aggravated by virustatic agents like azidothymidine. As an alternative therapeutic attempt, three derivatives of an antisense oligodeoxynucleotide (ODN) against the splice acceptor site of the tat gene have been shown to inhibit HIV replication in vitro. This study was aimed at examining whether these agents are toxic to the hematopoietic progenitor cells. To this end, bone marrow cells from HIV-positive and healthy persons were depleted from adherent cells to eliminate fibroblasts. In further experiments, the cells were additionally enriched for CD34-positive hematopoietic progenitor cells or were depleted from delta TCS-1-positive T lymphocytes. At concentrations of 1.25-10 microM, the three antisense ODN did not inhibit any erythrocyte or granulocyte-monocyte colony growth from CD34-positive cells, either from the HIV-positive or from the HIV-negative cohort. In contrast to azidothymidine, which served as inhibitory control, a significant increase of colony growth was seen after depletion of fibroblasts, of delta TCS-1-positive cells, or without cell separation. In conclusion, the three oligodeoxynucleotides do not exert any hematotoxic effect but do increase colony formation from low-density bone marrow cells in vitro and could therefore be useful in future clinical studies.