Fibroblast growth factor-2 promotes in vitro activation of cat primordial follicles.

This study evaluated the effect of fibroblast growth factor-2 (FGF-2) on the morphology, primordial follicle activation and growth after in vitro culture of domestic cat ovarian tissue. Ovaries (n = 12) from prepubertal domestic cats were collected and fragmented. One fragment was fixed for histological analysis (fresh control). The remaining fragments were incubated in control medium alone or with 10, 50 or 100 ng/ml FGF-2 for 7 days. After in vitro culture, the following endpoints were analyzed: morphology, activation by counting primordial and developing follicles, and growth (follicle and oocyte diameters). Treatment with 100 ng/ml FGF-2 maintained (P > 0.05) the percentage of normal follicles similar to fresh control. Follicle survival was greater (P < 0.05) after culture in 100 ng/ml FGF-2 than in 50 ng/ml FGF-2. The percentage of primordial follicles decreased (P < 0.05) and the percentage of developing follicles increased (P < 0.05) in all treatments compared with fresh tissue. The proportion of developing follicles increased (P < 0.05) in tissues incubated with 100 ng/ml FGF-2 compared with control medium and other FGF-2 concentrations. Furthermore, culture in 10 or 100 ng/ml FGF-2 resulted in increased (P < 0.05) follicle and oocyte diameters compared with fresh tissues and MEM+. In conclusion, FGF-2 at 100 ng/ml maintains follicle survival and promotes the in vitro activation and growth of cat primordial follicles.

[Successful treatment of a geriatric COVID-19 patient with severe chest trauma : An interdisciplinary case report]. / Erfolgreiche Behandlung des schweren Thoraxtraumas einer geriatrischen COVID-19-Patientin : Ein Fallbericht von interdisziplinärer Bedeutung.

The coronavirus disease 2019 (COVID-19) has spread rapidly worldwide and leads to high morbidity and mortality. Clinical experience regarding the surgical management in COVID-19 patients is limited. We report the interdisciplinary approach in a COVID-19 patient with severe thoracic trauma and pulmonary symptoms, who was admitted to the emergency unit after blunt chest trauma with dislocated serial rib fractures and concomitant hemothorax.

Program on high value cost-conscious education in intensive care: Educational program on prediction of outcome and cost awareness on Intensive Care admission.

BACKGROUND: Intensive Care (ICU) involves extended and long lasting support of vital functions and organs. However, current training programs of ICU residents mainly focus on extended support of vital functions and barely involve training on cost-awareness and outcome. We incorporated an educational program on high-value cost-conscious care for residents and fellows on our ICU and measured the effect of education. METHODS: A cohort study with factorial survey design, in which ICU residents and fellows were asked to evaluate clinical vignettes, was performed on the mixed surgical-medical ICU of the Amsterdam University Medical Centre. Residents were offered an educational program focusing on outcome and costs of ICU care. Before and after the program they filled out a questionnaire, which consisted of 23 vignettes, in which known predictors of outcome of community acquired pneumonia (CAP), pancreatitis, acute respiratory distress syndrome (ARDS) and cardiac arrest were presented, together with varying patient factors (age, body mass index (BMI), acute kidney failure (AKI) and haemato-oncological malignancy). Participants were asked to either admit the patient or estimate mortality. RESULTS: BMI, haemato-oncological malignancy and severity of pancreatitis were discriminative for admission to ICU in clinical vignettes on pancreatitis and CAP. After education, only severity of pancreatitis was judged as discriminative. Before the intervention only location of cardiac arrest (in- vs out of hospital) was distinctive for mortality, afterwards this changed to presence of haemato-oncological malignancy. CONCLUSION: We incorporated an educational program on high-value cost-conscious care in the training of ICU physicians. Based on our vignette study, we conclude that the improvement of knowledge of costs and prognosis after this program was limited.

A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias.

BACKGROUND: Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 (T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). METHODS: We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months. RESULTS: Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event. CONCLUSIONS: Ponatinib had significant antileukemic activity across categories of disease stage and mutation status. (Funded by Ariad Pharmaceuticals and others; PACE ClinicalTrials.gov number, NCT01207440 .).

Perioperative management and outcome of fracture treatment in patients with haemophilia without inhibitors.

INTRODUCTION: Fractures in persons with haemophilia (PWH) are not uncommon and require an interdisciplinary approach to maintain haemostasis during surgical treatment. AIM: The aim of this study was to evaluate the perioperative management and outcome in PWH following fracture fixation compared to a matched non-haemophilic control group. METHODS: A cohort of 44 PWH who underwent 46 surgical fracture fixations was retrospectively compared to 46 non-haemophilic patients (matched-pair controls). Patients were classified according to the fracture localization: (i) proximal upper extremity (PrUEx; n = 7), (ii) distal upper extremity (DiUEx; n = 12), (iii) proximal lower extremity (PrLEx; n = 13) and (iv) distal lower extremity (DiLEx; n = 14). Both groups were assessed for length of hospital stay, duration of surgery, drainage use and complication rates. RESULTS: There was no significant difference regarding the duration of the preoperative hospital stay between PWH and controls. Only PWH who were operated at the DiUEx stayed significantly longer in hospital (4.8 ± 3.7 days) than controls (2.2 ± 2.3 days; P = 0.039). Operation time was significantly longer in PWH with fractures treated at the DiLEx (64.9 ± 26.6 min) compared to the controls (49.8 ± 37.9 min; P = 0.035). Neither frequency nor duration of surgical drainage placement differed significantly between the two groups. The overall complication rate in both groups was low without a statistically significant difference. CONCLUSION: An optimal interdisciplinary perioperative management provided the surgical treatment of fractures in PWH can be performed safely with a low complication rate.

Outcome after total knee arthroplasty in haemophilic patients with stiff knees.

INTRODUCTION: Advanced haemophilic arthropathy of the knee is associated with progressive joint stiffness. Results after total knee arthroplasty (TKA) in stiff knees are considered to be inferior compared to those with less restricted preoperative range of motion (ROM). There is only very limited data on the results of primary TKA in haemophilic patients with stiff knees. AIM: The purpose of this retrospective study was to evaluate the clinical outcome after TKA performed in haemophilic patients with preoperative ROM of 50° or less. METHODS: Twenty one patients (23 knees) undergoing TKA with stiff knees were retrospectively evaluated. Mean follow-up was 8.3 years (range, 2-25). Clinical assessment included ROM, degree of flexion contracture and complication rate. Functional evaluation and pain status were assessed using the Knee Society's Scoring System (KSS). RESULTS: Range of motion improved from 26.7° preoperatively to 73.0° postoperatively. Flexion contracture decreased from 21.7° to 8.3°. KSS increased from 22.9 to 72.9 points. Evaluation of pain revealed a decrease from 8.4 points preoperatively to 2.1 points postoperatively. All these differences were statistically significant (P < 0.005). The complication rate was 8.7% including one late periprosthetic infection, and one aseptic implant loosening. Nine patients who required VY-quadricepsplasty for knee exposure developed a mean postoperative extensor lag of 7°. CONCLUSION: Total knee arthroplasty in haemophilic patients presenting with stiff knees results in significant improvement of function and reduction in pain. Although the clinical outcome is inferior compared to nonstiff knees reported in the literature, joint replacement surgery can be successfully performed in this particular group of patients.

Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples.

The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy.

Total ankle replacement in patients with haemophilia and virus infections--a safe alternative to ankle arthrodesis?

Despite reliable results of ankle fusion for advanced haemophilic arthropathy, total ankle replacement (TAR) may be functionally advantageous. There is only very limited literature data available on TAR in patients with haemophilia. The objective of this study is to evaluate the short- and mid-term results after TAR in patients with end-stage haemophilic ankle arthropathy and concomitant virus infections. In a retrospective study, results after eleven TAR in 10 patients with severe (n = 8) and moderate (n = 2) haemophilia (mean age: 49 ± 7 years, range, 37-59) were evaluated at a mean follow-up of 3.0 years (range, 1.2-5.4). Nine patients were positive for hepatitis C, five were HIV-positive. Range of motion (ROM), AOFAS-hindfoot-score, pain status (visual analogue scale, VAS) as well as patient satisfaction were evaluated. In two cases deep prosthesis infection occurred leading to the removal of the implant. In the remaining eight patients the mean AOFAS score improved significantly from 21.5 to 68.0 points (P < 0.0005), the VAS score decreased significantly from 7.6 to 1.9 points (P < 0.0005). ROM increased from 23.2 to 25.0 degrees (P = 0.51). At final follow-up all patients without any complications were satisfied with the postoperative results. Radiographic examination did not reveal any signs of prosthetic loosening. TAR is a viable surgical treatment option in patients with end-stage ankle osteoarthritis due to haemophilia. It provides significant pain relieve and high patient satisfaction. However, due to the increased risk of infection and lack of long-term results, TAR particularly in patients with severe haemophilia and virus infections should be indicated carefully.

The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury.

BACKGROUND AND OBJECTIVE: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Specific therapy is lacking. We assessed whether C1-inhibitor attenuates lung injury in a 'two-hit' TRALI model. METHODS: Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC-I antibodies. In the intervention group, C1-inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained. RESULTS: Injection of MHC-I antibodies induced TRALI, illustrated by an increase in wet-to-dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1-inhibitor resulted in increased pulmonary C1-inhibitor levels with high activity. C1-inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro-inflammatory mediators were unaffected. CONCLUSION: In a murine model of TRALI, C1-inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.

Evaluation of a multi-center randomised clinical trial on prophylactic transfusion of fresh frozen plasma: implications for future trials.

BACKGROUND: Prophylactic use of fresh frozen plasma (FFP) in critically ill patients with a coagulopathy is common. However, a lack of evidence of efficacy has resulted in a call for trials on the benefit of FFP in these patients. To date, conducting a trial on this subject has not been successful. Recently, a multi-center randomised trial was stopped prematurely due to slow inclusion. OBJECTIVE: To assess clinicians' opinions regarding a trial on prophylactic administration of FFP in coagulopathic critically ill patients who need to undergo an intervention. METHODS: A survey among 55 intensivists who all participated in a randomised trial on the risks and benefits of FFP in critically ill patients. RESULTS: Response rate was 84%. Majority of respondents indicated that international normalised ratio (INR) should be assessed before insertion of a central venous catheter (CVC) (61%), chest tube (89%) or tracheostomy (91%). Reasons to withhold transfusion of FFP to non-bleeding critically ill patients are risk of transfusion-related acute lung injury (TRALI) (46%), fluid overload (39%) and allergic reaction (24%). Although, the majority of respondents expressed the opinion that the trial was clinically relevant, 56% indicated that ≥1 patient subgroups should have been excluded from participation. CONCLUSION: Intensivists express the need for more evidence on the prophylactic use of FFP in coagulopathic critically ill patients. However, lack of knowledge about FFP and personal beliefs about the preferable transfusion strategy among clinicians, resulted in premature termination of a clinical trial on this topic.

[Evaluation of a 2D fluoroscopy-based navigation system for insertion of femoral neck screws. An experimental study]. / Evaluation eines 2-D-fluoroskopiebasierten Navigationssystems zur Implantation von Schenkelhalsschrauben. Eine experimentelle Studie.

INTRODUCTION: The aim of this study was the evaluation of a new computer-assisted planning and navigation system based on 2D-fluoroscopy for guidewire insertion in order to perform cannulated screw placement into the femoral neck. The image acquisition process was supported by a radiation-saving procedure called Zero-dose C-arm navigation. MATERIAL AND METHODS: In the context of a sawbone study, we performed insertion of 3 cannulated screws positioned under navigation control as well as using the conventional technique in 12 sawbones. Both procedures were performed using open and closed techniques. RESULTS: The computer-assisted technique significantly reduced the amount of intraoperative fluoroscopic images (open technique: -14±3 images, closed technique: -29.4±6 images). Drilling attempts were reduced in the computer-assisted groups (open technique: -1.2±1 attempts, closed technique: -1.7±1.5 attempts) and the femoral neck area covered by the screws was greater in the navigation-assisted groups (open technique: +32.1±16.3 mm(2), closed technique: +32.6±14.9 mm(2)), There was no difference concerning parallelism of the screws or perforation of femoral neck or head. The operation time was significantly longer in the navigation-assisted groups (open technique: +24.2±2.1 min, closed technique: +22.8±5.8 min). CONCLUSION: The addition of computer-assisted planning and surgical guidance supported by Zero-dose C-arm navigation can be useful for the fixation of medial femoral neck fractures with cannulated screws. Further studies with the goal of reducing the operation time are indispensable before integrating this navigation system into the clinical workflow.

Evaluation of a new computer-assisted surgical planning and navigation system based on two-dimensional fluoroscopy for insertion of a proximal femoral nail: an experimental study.

Pertrochanteric femoral fractures are common and intramedullary nailing is an accepted method for their surgical treatment. Accurate placement of the implant is essential to ensure fixation. The conventional technique can require multiple guide wire passes, and relies heavily on fluoroscopy. A computer-assisted planning and navigation system based on two-dimensional fluoroscopy for guide wire placement in the femoral neck has been developed, in order to perform intramedullary pertrochanteric fracture fixation using the proximal femoral nail (PFNA). The planning process was supported by a 'zero-dose C-arm navigation' system. The PFNA was inserted into 12, intact, femoral sawbones guided by the computer-based navigation, and into 12, intact, femoral sawbones using a conventional fluoroscopic-assisted technique. Guide wire and subsequent blade placement in the femoral neck was evaluated. The computer-assisted technique achieved a significant decrease in the number of required fluoroscopic images and in the number of guide wire passes. The obtained average blade placement accuracy in the femoral neck was equivalent to the conventional technique. The operation time was significantly longer in the navigation-assisted group. The addition of computer-assisted planning and surgical guidance to the intramedullary nailing of pertrochanteric femoral fractures offers a number of clinical benefits based on the results of this sawbone study. Further studies including fractured sawbones and cadaver models with extension of the navigation process to all steps of PFNA introduction and with the goal of reducing operation time are indispensable before integration of this navigation system into clinical practice.

[Endoprosthetics of the radial column after trauma]. / Endoprothetischer ersatz des radialen pfeilers nach trauma.

Non-displaced fractures of the radius head are in most cases treated conservatively. Open reduction and anatomical internal fixation of displaced radius head fractures is the method of choice. In comminuted fractures of the radius head (Mason type III and type IV) replacement with a radius head prosthesis achieves joint stability and prevents secondary complications, such as valgus elbow deformity and proximal radial migration. Modern anatomically formed prostheses show promising results in the medium-term view. Typical complications after radius head replacement are limited range of motion in the elbow joint, arthritis of the capitulum and heterotopic ossifications. In cases of capitulum arthritis, capitulum prostheses were developed to resurface the lateral compartment of the elbow joint. Short-term results are encouraging with improvements in pain and range of movement.

Melatonin improves development, mitochondrial function and promotes the meiotic resumption of sheep oocytes from in vitro grown secondary follicles.

The aim of this study was to evaluate follicular survival and development of ovine isolated secondary follicles cultured in medium containing fixed or sequential concentrations of melatonin and further oocyte maturation. Isolated secondary follicles were cultured for 18 days in α-MEM+ alone (control) or with different concentrations of melatonin (100, 500 or 1000 pg/mL) or sequential concentrations of melatonin (Mel Seq: Day 6 = 100; Day 12 = 500; Day 18 = 1000 pg/mL). The percentages of morphologically normal follicles and antral cavity formation increased significantly in 1000 pg/mL melatonin compared to the other treatments. After 18 days, 1000 pg/mL melatonin (Mel 100) showed a greater (P < 0.05) follicular diameter than α-MEM+, 100 and 500 pg/mL melatonin. In addition, the concentration of 500 pg/mL melatonin showed a higher (P < 0.05) percentage of fully grown oocytes than α-MEM+, Mel 100 and Mel Seq treatments. After oocyte maturation, the levels of ROS were lower (P < 0.05) in 1000 pg/mL melatonin (Mel 1000) than in other treatments. Both Mel 1000 and Mel Seq treatments showed significantly higher levels of mitochondrial activity than other treatments. There were no significant differences between 500 and 1000 pg/mL melatonin regarding meiotic stages. In conclusion, the concentration of 1000 pg/mL melatonin maintains survival, promotes follicular development and increases the levels of active mitochondria after in vitro culture of sheep secondary follicles. Moreover, this concentration promotes the meiotic competence of oocytes and decreases the production of ROS during oocyte maturation.

Effects of melatonin on the in vitro growth of early antral follicles and maturation of ovine oocytes.

This study aimed to evaluate the effect of melatonin on the in vitro culture and maturation of isolated sheep early antral follicles. Isolated early antral follicles were cultured for 12 d in α-minimum essential medium (MEM+) alone (control) or α-MEM+ added with fixed different concentrations (100, 500, or 1,000 pg/mL) or a sequential concentration of melatonin (MelSeq; day 6 = 100; day 12 = 500 pg/mL). The percentage of morphologically normal follicles was higher (P < 0.05) in 500 pg/mL melatonin than the other treatments at 6 d. Mel 500 also showed a higher rate of fully grown oocytes (P < 0.05) than other treatments. After in vitro culture, reactive oxygen species (ROS) levels in oocytes were similar between Mel 500 and MelSeq, with both being lower (P < 0.05) than other treatments. Oocytes cultured in both Mel 500 and Mel 1000 showed glutathione peroxidase levels similar (P > 0.05) to the control group and higher (P < 0.05) than other treatments. Mitochondrial activity was similar (P > 0.05) among control, Mel 500, and Mel 1000 treatments. Mel 500 treatment presented a higher percentage of germinal vesicle breakdown oocytes than the control group and similar percentages to the other treatments. Follicles cultured in melatonin followed by oocyte maturation with the addition of 500 pg/mL melatonin in maturation medium showed increased (P < 0.05) levels of mitochondrial activity compared to α-MEM+ alone. In conclusion, the concentration of 500 pg/mL of melatonin promotes development and decreases ROS levels of ovine oocytes from in vitro grown early antral follicles. Moreover, melatonin increases mitochondrial activity and promotes the acquisition of meiotic competence of these oocytes.

Kink far below the Fermi level reveals new electron-magnon scattering channel in Fe.

Many properties of real materials can be modeled using ab initio methods within a single-particle picture. However, for an accurate theoretical treatment of excited states, it is necessary to describe electron-electron correlations including interactions with bosons: phonons, plasmons, or magnons. In this work, by comparing spin- and momentum-resolved photoemission spectroscopy measurements to many-body calculations carried out with a newly developed first-principles method, we show that a kink in the electronic band dispersion of a ferromagnetic material can occur at much deeper binding energies than expected (Eb = 1.5 eV). We demonstrate that the observed spectral signature reflects the formation of a many-body state that includes a photohole bound to a coherent superposition of renormalized spin-flip excitations. The existence of such a many-body state sheds new light on the physics of the electron-magnon interaction which is essential in fields such as spintronics and Fe-based superconductivity.

Predictors of short-term and long-term mortality in critically ill patients admitted to the intensive care unit following allogeneic stem cell transplantation.

Historically, the mortality of patients admitted to the ICU after allogeneic stem cell transplantation (alloSCT) is high. Advancements in transplantation procedures, infectious monitoring and supportive care may have improved the outcome. This study aimed to determine short-term and long-term mortality after ICU admission of patients after alloSCT and to identify prognostic clinical and transplantation-related determinants present at ICU admission for long-term outcome. A multicenter cohort study was performed to determine 30-day and 1-year mortality within 2 years following alloSCT. A total of 251 patients were included. The 30-day and 1-year mortality was 55% and 80%, respectively. Platelet count <25 × 109/L (OR: 2.26, CI: 1.02-5.01) and serum bilirubin >19 µmol/L (OR: 2.47 CI: 1.08-5.65) at admission, other donor than a HLA-matched-related or HLA-matched-unrelated donor (OR: 4.59, CI: 1.49-14.1) and vasoactive medication within 24 h (OR: 2.35, CI: 1.28-4.31) were associated with increased 30-day mortality. Other donor than a HLA-matched-related or HLA-matched-unrelated donor (OR: 1.9, CI: 1.13-3.19), serum bilirubin >77 (OR: 2.05, CI: 1.28-3.30) and vasoactive medication within 24 h (OR: 1.65, CI: 1.12-2.43) were associated with increased 1-year mortality. Neutropenia was associated with decreased 30-day and 1-year mortality (OR: 0.29, CI: 0.14-0.59 and OR: 0.70, CI: 0.48-0.98). Myeloablative conditioning and T cell-depleted transplantation were not associated with increased mortality.

Characterization of a reference material for BCR-ABL (M-BCR) mRNA quantitation by real-time amplification assays: towards new standards for gene expression measurements.

Monitoring of BCR-ABL transcripts has become established practice in the management of chronic myeloid leukemia. However, nucleic acid amplification techniques are prone to variations which limit the reliability of real-time quantitative PCR (RQ-PCR) for clinical decision making, highlighting the need for standardization of assays and reporting of minimal residual disease (MRD) data. We evaluated a lyophilized preparation of a leukemic cell line (K562) as a potential quality control reagent. This was found to be relatively stable, yielding comparable respective levels of ABL, GUS and BCR-ABL transcripts as determined by RQ-PCR before and after accelerated degradation experiments as well as following 5 years storage at -20 degrees C. Vials of freeze-dried cells were sent at ambient temperature to 22 laboratories on four continents, with RQ-PCR analyses detecting BCR-ABL transcripts at levels comparable to those observed in primary patient samples. Our results suggest that freeze-dried cells can be used as quality control reagents with a range of analytical instrumentations and could enable the development of urgently needed international standards simulating clinically relevant levels of MRD.

Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma.

The FIP1L1-PDGFRA fusion gene has been described in patients with eosinophilia-associated myeloproliferative disorders (Eos-MPD). Here, we report on seven FIP1L1-PDGFRA-positive patients who presented with acute myeloid leukemia (AML, n=5) or lymphoblastic T-cell non-Hodgkin-lymphoma (n=2) in conjunction with AML or Eos-MPD. All patients were male, the median age was 58 years (range, 40-66). AML patients were negative for common mutations of FLT3, NRAS, NPM1, KIT, MLL and JAK2; one patient revealed a splice mutation of RUNX1 exon 7. Patients were treated with imatinib (100 mg, n=5; 400 mg, n=2) either as monotherapy (n=2), as maintenance treatment after intensive chemotherapy (n=3) or in overt relapse 43 and 72 months, respectively, after primary diagnosis and treatment of FIP1L1-PDGFRA-positive disease (n=2). All patients are alive, disease-free and in complete hematologic and complete molecular remission after a median time of 20 months (range, 9-36) on imatinib. The median time to achievement of complete molecular remission was 6 months (range, 1-14). We conclude that all eosinophilia-associated hematological malignancies should be screened for the presence of the FIP1L1-PDGFRA fusion gene as they are excellent candidates for treatment with tyrosine kinase inhibitors even if they present with an aggressive phenotype such as AML.

[A young woman from Cameroon with rectal blood loss, intestinal schistosomiasis and rectosigmoid carcinoma]. / Een jonge vrouw uit kameroen met rectaal bloedverlies, intestinale schistosomiasis en rectosigmoïdcarcinoom.

A 32-year-old woman from Cameroon presented with rectal blood loss due to a focally infiltrating adenocarcinoma of the rectosigmoid in the presence of an active intestinal schistosomiasis (Schistosoma intercalatum). A correlation between chronic intestinal schistosomiasis and the development of colorectal cancer has been suggested in the literature, but is not uniformly accepted. However, the case presented here reinforces this suggestion. In a patient with rectal blood loss who comes from an area where intestinal schistosomiasis is endemic, the possibility of a colorectal carcinoma should be considered in the diagnosis.