Quantitative assessment of haemolysis secondary to modern infusion pumps.

BACKGROUND: Although most studies have shown that little haemolysis is induced by infusion pumps, there are some notable exceptions. Only limited data are available on the actual infusion pumps that are most used in hospitals in Quebec and elsewhere, namely, the Infusomat® Space (peristaltic), Plum A+™ (piston) and Colleague® CXE (shuttle) pumps. METHODS: Haemolysis and potassium levels were compared before and after the use of the three different infusion pumps. Using 135 units of packed red blood cells (RBCs) aged from 10 to 28 days, 27 measurements were taken for each pump at various flow rates (30, 60, 150, 300 and 450 ml/h) and were compared with measurements taken before using the pumps. The range of flow rates was chosen to cover those of paediatric and adult transfusions. RESULTS: The shuttle- and piston-type pumps resulted in low haemolysis levels. The peristaltic-type pump produced significantly more haemolysis, which worsened at low flow rates, but the absolute value of haemolysis remained within the range recommended by the regulatory agencies in North America and Europe. Approximately two-thirds of the haemolysis produced by the peristaltic-type pump seemed to be secondary to the use of an antisiphon valve (ASV) on the transfusion line recommended by the manufacturer. Potassium levels did not increase with the use of the pumps. CONCLUSION: Modern infusion pumps widely used in hospitals in Quebec and elsewhere produce non-threatening levels of haemolysis during the transfusion of packed RBCs aged from 10 to 28 days. ASVs appear to induce additional haemolysis, and we do not recommend using them for blood transfusion.

Synchronous metastatic skull base chordoma to the breast: case report and literature review.

CLINICAL SCENARIO: During routine staging work-up for a left breast mass, a 68-year-old woman complained of dysphagia and dysphonia. During further investigations, a left-sided lesion at the foramen magnum was observed on brain imaging. Both lesions were biopsied and showed a classical chordoma. MANAGEMENT: The skull-base lesion and the breast lesion were surgically resected, and adjuvant radiotherapy was given. SUMMARY: Chordoma is a rare primary central nervous system tumour that seldom metastasizes. The lung is the most common site of metastasis. Synchronous breast metastasis from a skull-base chordoma is very rare, and a safe management option includes a maximum resection followed by adjuvant radiotherapy.

[Inherited primitive and secondary polycythemia]. / Polyglobulies héréditaires primitives et secondaires.

Myeloproliferative disorders and secondary polycythemia cover most of the polycythemia cases encountered in daily practice. Inherited polycythemias are rare entities that have to be suspected when the classical causes of acquired polycythemia have been ruled out. Recent advances were made in the understanding of these pathologies, which are still little known to the physicians. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of inherited polycythemia.

A Canadian national expert consensus on neoadjuvant therapy for breast cancer: linking practice to evidence and beyond.

BACKGROUND: Use of the neoadjuvant approach to treat breast cancer patients has increased since the early 2000s, but the overall pathway of care for such patients can be highly variable. The aim of our project was to establish a multidisciplinary consensus among clinicians with expertise in neoadjuvant therapy (nat) for breast cancer and to determine if that consensus reflects published methods used in randomized controlled trials (rcts) in this area. METHODS: A modified Delphi protocol, which used iterative surveys administered to 85 experts across Canada, was established to obtain expert consensus concerning all aspects of the care pathway for patients undergoing nat for breast cancer. All rcts published between January 1, 1967, and December 1, 2012, were systematically reviewed. Data extracted from the rcts were analyzed to determine if the methods used matched the expert consensus for specific areas of nat management. A scoring system determined the strength of the agreement between the literature and the expert consensus. RESULTS: Consensus was achieved for all areas of the pathway of care for patients undergoing nat for breast cancer, with the exception of the role of magnetic resonance imaging in the pre-treatment or preoperative setting. The levels of agreement between the consensus statements and the published rcts varied, primarily because specific aspects of the pathway of care were not well described in the reviewed literature. CONCLUSIONS: A true consensus of expert opinion concerning the pathway of care appropriate for patients receiving nat for breast cancer has been achieved. A review of the literature illuminated gaps in the evidence about some elements of nat management. Where evidence is available, agreement with expert opinion is strong overall. Our study is unique in its approach to establishing consensus among medical experts in this field and has established a pathway of care that can be applied in practice for patients receiving nat.

Concurrent chemoradiotherapy for locally advanced breast cancer-time for a new paradigm?

BACKGROUND: In cases of locally advanced breast cancer (labc), preoperative ("neoadjuvant") therapy was traditionally reserved to render the patient operable. More recently, neoadjuvant therapy, particularly chemotherapy, is being used in patients with operable disease to increase the opportunity for breast conservation. Despite the increasing use of preoperative chemotherapy, rates of pathologic complete response, a surrogate marker for disease-free survival, remain modest in patients with locally advanced disease and particularly so when the tumour is estrogen or progesterone receptor-positive and her2-negative. A new paradigm for labc patients is needed. In other solid tumours (for example, rectal, esophageal, and lung cancers), concurrent chemoradiotherapy (ccrt) is routinely used in neoadjuvant and adjuvant treatment protocols alike. RESULTS: The literature suggests that ccrt in labc patients with inoperable disease is associated with response rates higher than would be anticipated with systemic therapy alone. CONCLUSIONS: Ongoing trials in this field are eagerly awaited to determine if ccrt should become the new paradigm.

How does loss to follow-up influence cohort findings on HIV infection? A joint analysis of the French hospital database on HIV, Mortalité 2000 survey and death certificates.

OBJECTIVE: We aimed to retrieve the vital status of patients lost to follow-up (LFU), with no further visits for at least 12 months, for the 34,835 patients in the Agence Nationale de Recherche sur le SIDA CO4 French Hospital Database on HIV (ANRS CO4 FHDH) seen in 1999 and to examine how loss to follow-up might influence estimates of survival and the impact of delayed access to care (DAC) on survival. METHODS: The status of LFU patients was established by using the mid-2006 update of the FHDH in which their status 12 months after loss to follow-up was added when available and by matching with the Mortalité 2000-Epidemiological Centre for Medical Causes of Death (CépiDc) database, which included HIV-infected patients dying in 2000. We compared Kaplan-Meier and hazard ratio (HR) estimates before and after correction for the status of LFU patients. RESULTS: In the mid-2006 updated FHDH, of the patients seen in 1999, 7.5% were LFU: of these, 2.1% later returned for follow-up, with a median time without follow-up in an FHDH centre of 3.5 years, and 5.4% had no further FHDH visits whatsoever, of whom 29.8% died according to Mortalité 2000-CépiDc. After correction, the estimated 1-year survival rates following enrolment in 1999 differed between the original and updated analyses (97.1 vs. 95.9%, respectively; P=0.017); the estimates of mortality HRs associated with DAC did not differ during the first 6 months, but did differ for the 6-18-month period. CONCLUSIONS: Among LFU patients, 28.1% returned to follow-up after several years and at least 21.4% died, which led to a slight overestimation of both survival and the impact of DAC on survival.

Experimental quantum communication without a shared reference frame.

We present an experimental realization of a robust quantum communication scheme [Phys. Rev. Lett. 93, 220501 (2004)] using pairs of photons entangled in polarization and time. Our method overcomes errors due to collective rotation of the polarization modes (e.g., birefringence in optical fiber or misalignment), is insensitive to the phase's fluctuation of the interferometer, and does not require any shared reference frame including time reference, except the need to label different photons. The practical robustness of the scheme is further shown by implementing a variation of the Bennett-Brassard 1984 quantum key distribution protocol over 1 km optical fiber.

Unconditional security of a three state quantum key distribution protocol.

Quantum key distribution (QKD) protocols are cryptographic techniques with security based only on the laws of quantum mechanics. Two prominent QKD schemes are the Bennett-Brassard 1984 and Bennett 1992 protocols that use four and two quantum states, respectively. In 2000, Phoenix et al. proposed a new family of three-state protocols that offers advantages over the previous schemes. Until now, an error rate threshold for security of the symmetric trine spherical code QKD protocol has been shown only for the trivial intercept-resend eavesdropping strategy. In this Letter, we prove the unconditional security of the trine spherical code QKD protocol, demonstrating its security up to a bit error rate of 9.81%. We also discuss how this proof applies to a version of the trine spherical code QKD protocol where the error rate is evaluated from the number of inconclusive events.

Robust quantum communication using a polarization-entangled photon pair.

Noise and imperfection of realistic devices are major obstacles for implementing quantum cryptography. In particular, birefringence in optical fibers leads to decoherence of qubits encoded in photon polarization. We show how to overcome this problem by doing single qubit quantum communication without a shared spatial reference frame and precise timing. Quantum information will be encoded in pairs of photons using tag operations, which corresponds to the time delay of one of the polarization modes. This method is robust against the phase instability of the interferometers despite the use of time bins. Moreover synchronized clocks are not required in the ideal no photon loss case as they are necessary only to label the different encoded qubits.

Robust polarization-based quantum key distribution over a collective-noise channel.

We present two polarization-based protocols for quantum key distribution. The protocols encode key bits in noiseless subspaces or subsystems and so can function over a quantum channel subjected to an arbitrary degree of collective noise, as occurs, for instance, due to rotation of polarizations in an optical fiber. These protocols can be implemented using only entangled photon-pair sources, single-photon rotations, and single-photon detectors. Thus, our proposals offer practical and realistic alternatives to existing schemes for quantum key distribution over optical fibers without resorting to interferometry or two-way quantum communication, thereby circumventing, respectively, the need for high precision timing and the threat of Trojan horse attacks.

An exactly solvable Ogston model of gel electrophoresis. VI. Towards a theory for macromolecules.

In this article, we present a generalized version of our lattice model of low-field gel electrophoresis that allows us to treat the case of macromolecules such as short linear or circular oligomers and semi-flexible rods. We show that free-solution electrophoresis problems can be seen as random walks in the conformational space of the analyte. For sufficiently small molecules, our mathematical approach provides exact mobilities. In a quenched gel-like environment, however, both conformational and positional degrees of freedom must be used, but exact solutions can also be obtained. As an example, we then investigate several two-dimensional model gels, as well as a simple channel system where we see evidence of entropic effects that cannot be captured by the traditional Ogston concept of free volume.

Allogeneic transplantation for multiple myeloma: further evidence for a GVHD-associated graft-versus-myeloma effect.

We report a series of 37 consecutive patients with multiple myeloma (MM) who received an allograft between 1990 and 2000 at our institution. Median age was 47 years, and nearly 70% of patients were Durie-Salmon stage III. A median of five cycles of chemotherapy were given before transplant, with a median interval between diagnosis and transplant of 9.3 months. We report a nonrelapse mortality rate of 22% with a median follow-up period of 40 months, whereas complete remission (CR) rate at 12 months is estimated at 57%. Treatment failure rate and overall survival at 40 months are estimated at 52% and 32%, respectively. The number of chemotherapy cycles prior to allotransplantation achieved borderline statistical significance as a poor prognosis factor for overall survival (P = 0.05), while the presence of chronic graft-versus-host disease (cGVHD) was significantly correlated with CR achievement (P = 0.036). Our study confirms that early allografting in MM can yield toxicity rates significantly lower than those associated with historical cohorts, and supports the hypothesis that cumulative chemotoxicity has a negative influence on mortality and survival rates. More importantly, our study clearly demonstrates an association between cGVHD and CR and brings further evidence in favor of a graft-versus-myeloma effect.

Theory of DNA electrophoresis: a look at some current challenges.

Although electrophoresis is one of the basic methods of the modern molecular biology laboratory, new ideas are being suggested at an accelerated rate, in large part because of the pressing demands of the biomedical community. Although we now have, at least for some methods, a fairly good theoretical understanding of the physical mechanisms that lead to the observed peak spacings, widths and shapes, this knowledge is often too qualitative to be used to guide further technical developments and improvements. In this article, we review some selected elements of the current state of our theoretical ignorance, focusing mostly on DNA electrophoresis, and we offer several suggestions for further theoretical investigations.

Allogeneic bone marrow transplantation following busulfan-cyclophosphamide with or without etoposide conditioning regimen for patients with acute lymphoblastic leukaemia.

We have investigated the feasibility and efficacy of administering a radiation-free preparative regimen in the setting of allogeneic bone marrow transplantation (BMT) in 40 consecutive patients with acute lymphoblastic leukaemia (ALL). Busulfan (4 mg/kg/d x 4 d) and cyclophosphamide (50 mg/kg/d x 4 d) (BuCy4) were given in 29 patients and 11 received busulfan (4 mg/kg/d x 4 d), etoposide (60 mg/kg) and cyclophosphamide (60 mg/kg/d x 2 d) (BuCy+VP - 16). Median age was 22 years (range 1-50); 11 patients were children < or = 15 years of age. All children and 20 adults were at high risk of relapse pretransplant. Nine adults and one child died from transplant-related toxicity. 11 patients relapsed at a median of 11 months post-transplant (range 2-27). The 3-year Kaplan-Meier estimated probability of relapse was 42.1% and found to be significantly lower in patients with chronic GVHD (P = 0.03). 19 patients are leukaemia-free survivors with a median follow-up of 33 months (range 7-59). The Kaplan-Meier actuarial probability of disease-free survival at 3 years was 43% for all patients. 63.6% for children versus 30.2% for adults (P = 0.24) and 51.6% for patients transplanted in first remission versus 30.2% for those transplanted in subsequent remissions (P = 0.20).

Acute graft-versus-host disease prophylaxis with methotrexate and cyclosporine after busulfan and cyclophosphamide in patients with hematologic malignancies.

The combination of two powerful immunosuppressive agents, methotrexate (MTX) and cyclosporine (CSP), has resulted in a significant decrease in the morbidity and mortality after allogeneic bone marrow transplantation (BMT). However, the additive toxicities from ablative preparative regimens may lead to suboptimal use of this combined immunoprophylaxis. We evaluated the efficacy and feasibility of administering MTX/CSP with busulfan (4 mg/kg/d for 4 days) and cyclophosphamide (50 mg/kg/d for 4 days) (BuCy4) in 101 consecutive patients with hematologic malignancies categorized into high- and low-risk groups receiving HLA-matched marrow grafts. Postgrafting immunosuppression consisted of MTX short course (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11) and intravenous CSP (1.5 mg/kg every 12 hours). Eighty-three patients (82.1%) received 100% of MTX calculated dose and 87 (86.1%) achieved a CSP therapeutic level (250 to 600 ng/mL) within a median of 16 days. Seventy-three patients (72.2%) received optimal immunosuppressive therapy comprising a full MTX course and achieving CSP therapeutic concentrations. The Kaplan-Meier estimated incidence of grade II to IV acute graft-versus-host disease (GVHD) was 9.2% for all patients and 5.5% in patients receiving optimal GVHD prophylaxis. Eighty-nine patients (88.2%) survived > or = 100 days posttransplant and 43 (48.3%) developed chronic GVHD, the majority of which were de novo (31 of 43). The estimated incidence of relapse was 28.9% for all patients and 14.8% in the low-risk group, with a median follow-up of 24.5 months. High-risk features and the absence of chronic GVHD were significantly associated with relapse (P = .002 and .036, respectively) in multivariate analyses. Projected disease-free survival at 2 years was 52.3% for all patients and 65.2% in low-risk patients. Disease-free survival was significantly improved in optimally treated patients (P = .03) due to a lower incidence of early deaths from acute GVHD and infectious episodes. In conclusion, optimal delivery of MTX/CSP in association with BuCy4 resulted in a near complete abrogation of acute GVHD in HLA-matched transplants and a significantly improved disease-free survival.

Cytogenic characterization of primary refractory anemia.

Refractory anemia (RA) is the only myelodysplastic syndrome (MDS) devoid of quantitative marrow diagnostic criteria. The diagnosis rests mainly on the subjective identification of qualitative abnormalities according to the French-American-British criteria (FAB) involving one or more bone marrow hematopoietic cell lineages. The occurrence of nonrandom chromosome abnormalities remains the hallmark of the disease and the only means of investigation which confirms the disease objectively. With the purpose in mind to further characterize RA among MDS, we have undertaken a prospective high resolution banding chromosome analyses of bone marrow cells in patients with primary refractory anemia (PRA) with the aim of defining a cytogenetic phenotype and of assessing the clinical relevance of clonal abnormalities at initial diagnosis. Of 39 patients consecutively referred for chromosome analyses with a diagnosis of RA according to the FAB criteria, 27 patients had PRA and fulfilled our criteria for adequate chromosome analyses. Median age was 68 years. Fourteen of 27 patients (52%) had clonal chromosomal abnormalities at diagnosis. None of the patients showed a complex karyotype; 9/14 (64%) had a mixture of normal and abnormal cells. Interstitial or terminal deletions, involving chromosomes 5, 6, 7, 9, 11, 12, and 20, were found in 11/14 (79%) of the patients. Comparison of survival between patients with and without abnormalities showed no difference. The presence of clonal abnormalities did not predict transformation to acute myeloblastic leukemia (AML) nor was it associated with poor survival. In this study, patients with PRA were found to have a predominant pseudodiploid karyotypic pattern characterized by interstitial and/or terminal deletions as opposed to derivatives, specific and non-specific balanced translocations, or other structural and numerical abnormalities. We were unable to reveal any prognostic significance to the presence of these clonal abnormalities at initial diagnosis.

Chronic B-cell lymphocytosis.

Persistent elevation of lymphocyte counts is usually associated with a malignant monoclonal lymphoproliferative disease. Over the last 8 years, amongst patients investigated in our center for undetermined persistent lymphocytosis, a diagnosis of malignant lymphoproliferation was excluded in 6 cases as studies of surface membrane immunoglobulin light chains showed that they presented a polyclonal expansion of their B-lymphocyte pool. All patients were young-to-middle aged women presenting peculiar immunohematologic findings characterized by 1) persistent (2-7 yr) elevation of lymphocyte counts (4-14 x 10(9)/l), 2) presence of characteristic binucleated B cells on peripheral blood smears, 3) a normal bone marrow histology, 4) a polyclonal increase of serum IgM with low-to-normal IgG and IgA levels. Histologic examination of the spleen in 2 patients and lymph nodes in 1 showed a benign follicular lymphoid hyperplasia. The evolution was benign in every case. We suggest that chronic polyclonal B-cell lymphocytosis is a distinct clinicopathologic entity that should not be confused with malignant lymphoproliferative disorders.