Impact of intraoperative therapeutic plasma exchange on bleeding in lung transplantation.

BACKGROUND: Our program uses a desensitization protocol that includes intraoperative therapeutic plasma exchange (iTPE) for crossmatch-positive lung transplants, which improves access to lung transplant for sensitized candidates while mitigating immunologic risk. Although we have reported excellent outcomes for sensitized patients with the use of this protocol, concern for perioperative bleeding appears to have hindered broader adoption of it at other programs. We conducted a retrospective cohort study to quantify the impact of iTPE on perioperative bleeding in lung transplantation. METHODS: All first-time lung transplant recipients from 2014 to 2019 who received iTPE were compared to those who did not. Multivariable logistic regression was used to determine the association between iTPE and large-volume perioperative transfusion requirements (≥5 packed red blood cell units within 24 hours of transplant start), adjusted for disease type, transplant type, and extracorporeal membrane oxygenation or cardiopulmonary bypass use. The incidence of hemothorax (requiring reoperation within 7 days of lung transplant) and 30-day posttransplant mortality were compared between the 2 groups using chi-square test. RESULTS: One hundred forty-two patients (16%) received iTPE, and 755 patients (84%) did not. The mean number of perioperative pRBC transfusions was 4.2 among patients who received iTPE and 2.9 among patients who did not. iTPE was associated with increased odds of requiring large-volume perioperative transfusion (odds ratio 1.9; 95% confidence interval: 1.2-2.9, p-value = 0.007) but was not associated with an increased incidence of hemothorax (5% in both groups, p = 0.99) or 30-day posttransplant mortality (3.5% among patients who received iTPE vs 2.1% among patients who did not, p = 0.31). CONCLUSIONS: This study demonstrates that the use of iTPE in lung transplantation may increase perioperative bleeding but not to a degree that impacts important posttransplant outcomes.

Complement-Mediated Thrombotic Microangiopathy in Pregnancy: An Educational Case Report.

Rationale: Thrombotic microangiopathy (TMA) is a spectrum of rare diseases characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. Differentiating pre-eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome and atypical hemolytic uremic syndrome (aHUS) during pregnancy may be diagnostically challenging yet important as the treatment pathways differ. Most cases of aHUS are associated with dysregulation of the complement alternative pathway, for which current guidelines recommend prompt treatment with complement C5 inhibitor to prevent chronic sequelae. Here, we report a case of pregnancy-associated aHUS (p-aHUS) to highlight the challenging aspects of the diagnostic process and the importance of prompt treatment with complement inhibition to reduce the risk of poor outcomes. Presenting concerns: A 28-year-old woman was admitted to a local hospital for induction of vaginal delivery of twins at 34 weeks and 3 days of gestational age, due to intrauterine growth restriction (IUGR). She was previously healthy, and this current pregnancy was uncomplicated, except for the IUGR. Approximately, 10 hours after her induced delivery, she developed vomiting, epigastric pain, and hypertension. Diagnosis: She was initially suspected of having fulminant liver failure in the context of acute fatty liver of pregnancy versus pre-eclampsia/HELLP syndrome, due to evidence of elevated liver enzymes, acute kidney injury (AKI), thrombocytopenia, and hemoglobin levels trending down, for which the patient was initially treated conservatively. On day 2 post-delivery, she was transferred to our hospital for possible liver biopsy and management of liver failure. Upon transfer, dialysis was started due to anuric AKI; at the same time, her liver function spontaneously improved, while platelet count remained very low and hemoglobin levels continued to trend down. A full TMA work-up revealed low C3 levels; secondary causes of TMA were ruled out. The patient received a final diagnosis of p-aHUS. Complement genetic tests were also performed and did not identify any pathogenic variants. Interventions: Given the final diagnosis of p-aHUS, the patient was started on a C5 inhibitor (day 8 post-delivery). Her platelet count quickly normalized 2 days after the first dose, while the hemoglobin levels remained low for a longer period, likely due to retained products of conception. Outcomes: The patient was able to completely discontinue dialysis after approximately 3 months, however, her kidney function did not recover completely, despite all the other TMA markers normalizing (platelets count in range, negative hemolysis markers, and normal hemoglobin levels). Her estimated glomerular filtration rate (eGFR) was 23 mL/min/1.73 m2 at the 6-month follow-up. Teaching points: The diagnosis of p-aHUS can be challenging due to frequent overlapping symptoms and signs with other forms of pregnancy-associated TMA, leading to a delay of the treatment, which can affect the patient's outcome. Failure of TMA to improve in the postpartum period or occurring at this time, with negative ADAMTS13 and antiphospholipid antibody syndrome (APLAS) serologies should favor the diagnosis of p-aHUS. Early treatment with C5 inhibition should be considered in women with a diagnosis of p-aHUS. Patients need multidisciplinary and likely tertiary/quaternary care at centers where clinical experience, access to diagnostics and treatment initiation can begin without delay.

Justification: La microangiopathie thrombotique (MAT) est un spectre de maladies rares caractérisées par une thrombocytopénie, une anémie hémolytique microangiopathique et des lésions à différents organes. Pendant la grossesse, il peut être difficile de différencier la prééclampsie, le syndrome HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) et le syndrome hémolytique et urémique atypique (SHUa) d'un point de vue diagnostique, mais il est important de le faire, car les avenues de traitement diffèrent. La plupart des cas de SHUa sont associés à un dérèglement de la voie alterne du complément, pour lequel la recommandation actuelle est de privilégier un traitement rapide avec un inhibiteur de la fraction C5 du complément afin de prévenir les séquelles chroniques. Dans le présent article, nous présentons un cas de SHUa associé à une grossesse (SHUa-g) afin de mettre en évidence les difficultés associées au diagnostic et l'importance de traiter rapidement par inhibition du complément afin de réduire le risque de résultats défavorables. Présentation du cas: Une femme de 28 ans admise dans un hôpital local pour l'induction d'un accouchement vaginal de jumeaux à 34 semaines et 3 jours, en raison d'un retard de croissance intra-utérin (RCIU). La patiente était en bonne santé et la grossesse, à l'exception du RCIU, était sans complications. Environ dix heures après l'accouchement, la patiente a développé des vomissements, des douleurs épigastriques et de l'hypertension. Diagnostic: On a d'abord soupçonné une insuffisance hépatique fulminante liée soit à une stéatose hépatique aiguë de la grossesse ou encore à une prééclampsie/syndrome HELLP, en raison d'une élévation des enzymes hépatiques, d'une insuffisance rénale aiguë, d'une thrombocytopénie et d'une baisse de l'hémoglobine, pour lesquelles la patiente a initialement été traitée de façon conservatrice. Deux jours après l'accouchement, la patiente a été transférée à notre hôpital pour une possible biopsie du foie et la prise en charge d'une insuffisance hépatique. Après le transfert, une IRA anurique a justifié l'initiation de la dialyse. Au même moment, la fonction hépatique s'est améliorée spontanément, tandis que la numération plaquettaire est demeurée très faible et que les taux d'hémoglobine ont continué à baisser. Un bilan MAT complet a révélé de faibles taux de C3; les causes secondaires de MAT ont été écartées. La patiente a reçu un diagnostic final de SHUa-g. Des tests génétiques complémentaires n'ont pas permis d'identifier de variants pathogènes. Intervention: Compte tenu du diagnostic final de SHUa-g, un traitement avec un inhibiteur de C5 a été amorcé (au huitième jour après l'accouchement). La numération plaquettaire s'est rapidement normalisée deux jours après la première dose, mais les taux d'hémoglobine sont demeurés bas sur une plus longue période, probablement en raison de la rétention de produits de la conception. Résultats: La patiente a pu cesser complètement la dialyse environ trois mois plus tard, mais sa fonction rénale ne s'est pas complètement rétablie, malgré la normalisation de tous les autres marqueurs de MAT (numération plaquettaire dans les normales, marqueurs d'hémolyse négatifs, taux d'hémoglobine normaux). Son débit de filtration glomérulaire estimé (DFGe) s'établissait à 23 ml/min/1.73 m2 lors du suivi à six mois. Enseignements tirés: Le chevauchement fréquent des symptômes et signes cliniques des autres formes de MAT associées à la grossesse rend parfois difficile le diagnostic du SHUa-g, ce qui peut retarder le traitement et affecter l'évolution clinique. L'absence d'amélioration d'une MAT dans la période postpartum, ou sa survenue à ce moment, couplée à des sérologies négatives pour ADAMTS13 et pour le syndrome des anticorps antiphospholipides (SAPL) devrait plaider en faveur d'un diagnostic de SHUa-g. Un traitement précoce par inhibition de C5 doit être envisagé chez les femmes qui reçoivent un diagnostic de SHUa-g. Ces patientes requièrent des soins multidisciplinaires, et probablement tertiaires/quaternaires, dans des centres où l'expérience clinique, l'accès au diagnostic et l'initiation du traitement sont rapidement accessibles.

Propensity Score Matching Analysis Comparing the Efficacy and Steroid Tapering Benefit of Extracorporeal Photopheresis to Best Available Therapy in Third-Line or Beyond Treatment for Chronic GvHD.

Graft-versus host disease (GVHD) is one of the major limitations to allogeneic hematopoietic stem cell transplantation (HCT). Although corticosteroids with calcineurin inhibitors are established first line-therapy for chronic graft-versus-host disease (cGVHD), approximately one-half of cGVHD patients are refractory to corticosteroid therapy. The goal of the present study was to compare treatment outcomes of patients treated with extracorporeal photopheresis (ECP) and best available therapy (BAT) as third-line or beyond treatment for cGVHD. Using propensity score matching (PSM), treatment outcomes were compared between ECP-treated patients (n = 74) and a historical cohort of cGVHD patients treated with BAT (n = 132). By adjusting for unbalanced risk factors between the groups, including GVHD severity at the start of therapy, acute GVHD history, and baseline corticosteroid dose, 62 patients were balanced and selected for PSM. In the PSM cohort, the ECP group showed a 12-month failure-free survival (FFS) rate of 70.1% versus 32.5% in the BAT group (P < .0001; hazard rate [HR], .214), and 93.1% 12 months' overall survival (OS) rate of 93.1% versus 68.1% in the BAT group (P = .0249; HR, .3811); multivariate analysis confirmed ECP's superior FFS and OS compared with BAT. Generalized linear model analysis showed faster tapering of corticosteroids and higher rates of prednisone discontinuation in the ECP versus BAT PSM groups in the first 6 months. The ECP group also had a higher percentage of prednisone discontinuation, by 6% at month 0, by 14.9% at month 3, and by 22.5% at month 6. The current study demonstrates superior FFS, OS, and steroid tapering efficacy for ECP compared with BAT as third-line therapy or beyond in cGVHD patients.

Single centre retrospective analysis of extracorporeal photopheresis (ECP) therapy in patients heavily pre-treated for chronic graft-versus-host disease (cGvHD) with steroid failure.

BACKGROUND: Extracorporeal photopheresis (ECP) is recommended as a second- or later-line therapy for chronic GvHD (cGvHD). Benefits include reasonable response with avoidance of intense systemic immunosuppression, which can translate into lowering the risk of systemic toxicity and opportunistic infection. METHODS: We evaluated 75 patients treated with ECP for cGvHD from 2007 to 2021 at Princess Margaret Cancer Centre, and analyzed overall response rate (ORR) and clinical benefit (CB) at 3, 6 and 12 months plus other long-term treatment outcomes. RESULTS: With a median follow-up of 72 months, a gradual increase in ORR was noted over time: 21% (16 out of 75 patients), 57% (36/63) and 70% (32/46) at month 3, 6 and 12, respectively. Gradual increase in CB was also observed over time with CB rate of 23% (17/75), 62% (39/63), and 76% (35/46) at months 3, 6 and 12, respectively. A total of 27 failures (36%) were noted, due to: 1) ECP resistance requiring switch to other therapy (n = 14, 19%), 2) non-relapse mortality (n = 10, 13%), 3) relapse of primary disease (n = 1, 1%) or 4) ECP procedure-related complication (n = 1, 1%, line infection), with 20 deaths (27%) observed. Failure-free survival (FFS) and overall survival (OS) rates were 68.3% and 85.9% at 12 months, respectively. After starting ECP, the proportions of patients who completely discontinued steroids were 17%, 32%, and 64% at months 3, 6 and 12, respectively. CONCLUSION: ECP is an effective treatment option for heavily pre-treated cGvHD patients.

Characterizing the process of urgent referrals and transfers to a large tertiary care apheresis centre in Ontario: A retrospective database review.

BACKGROUND: Therapeutic plasma exchange (TPE) and red blood cell exchange (RBCX) are life-saving apheresis procedures offered in 7 Ontario hospitals. Most referrals are directed by CritiCall Ontario (CritiCall), a 24/7 service funded by the Ontario Ministry of Health and Long-Term Care. We used CritiCall data to examine referral requests, acceptances, and transfers for urgent apheresis to our centre. METHODS: Retrospective CritiCall referral and transfer data for urgent apheresis between October 2013 and December 2018 were included. Continuous variables were analyzed by linear regression. Categorical variables were analyzed using nonparametric tests. RESULTS: Eighty-five cases (52 TPE, 33 RBCX) were identified. Median patient age was 52 years (interquartile range [IQR] 32) for TPE, 29 years (IQR 18) for RBCX. Most patients (58%) were female. Total time from referral to arrival at our centre was 243 (IQR 166) minutes. The greatest proportion of this total was from patient acceptance to arrival (169 [IQR 112] minutes). Median distance between referring and accepting centres was 39 (IQR 30) kilometres, with ground transportation used most often. Multiple linear regression examining factors that contribute to total time demonstrated that the number of physicians contacted prior to patient acceptance and inter-hospital distance were independently associated (p = 0.007 and p = 0.048, respectively). INTERPRETATION: Addressing modifiable factors to reduce time is important given that time to initiate treatment is associated with better outcomes. Quality improvement strategies should be aimed at coordinated provincial resource sharing, pairing referrals with nearest available apheresis centres, and creating efficiency in the interval between patient acceptance and arrival.

Outcomes after flow cytometry crossmatch-positive lung transplants managed with perioperative desensitization.

Our program previously reported successful outcomes following virtual crossmatch (VXM)-positive lung transplants managed with perioperative desensitization, but our ability to stratify their immunologic risk was limited without flow cytometry crossmatch (FCXM) data before 2014. The aim of this study was to determine allograft and chronic lung allograft dysfunction (CLAD)-free survival following VXM-positive/FCXM-positive lung transplants, which are performed at a minority of programs due to the high immunologic risk and lack of data on outcomes. All first-time lung transplant recipients between January 2014 and December 2019 were divided into 3 cohorts: VXM-negative (n = 764), VXM-positive/FCXM-negative (n = 64), and VXM-positive/FCXM-positive (n = 74). Allograft and CLAD-free survival were compared using Kaplan-Meier and multivariable Cox proportional hazards models. Five-year allograft survival was 53% in the VXM-negative cohort, 64% in the VXM-positive/FCXM-negative cohort, and 57% in the VXM-positive/FCXM-positive cohort (P = .7171). Five-year CLAD-free survival was 53% in the VXM-negative cohort, 60% in the VXM-positive/FCXM-negative cohort, and 63% in the VXM-positive/FCXM-positive cohort (P = .8509). This study confirms that allograft and CLAD-free survival of patients who undergo VXM-positive/FCXM-positive lung transplants with the use of our protocol does not differ from those of other lung transplant recipients. Our protocol for VXM-positive lung transplants improves access to transplant for sensitized candidates and mitigates even high immunologic risk.

Blood-brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood-brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity < 10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral computed tomography perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range, 21-77 years). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD], 25) × 109/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100 g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100 g, with a mean difference of -0.312 mL/min/100 g (95% confidence interval: -0.4729 to -0.1510; P = .0032). In this pilot study of patients with iTTP, pathologically increased BBB permeability was evident, and although there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications.

Long-term outcomes of sensitized lung transplant recipients after peri-operative desensitization.

The Toronto Lung Transplant Program has been using a peri-operative desensitization regimen of plasma exchange, intravenous immune globulin, and antithymocyte globulin in order to accept donor-specific antibody (DSA)-positive lung transplants safely since 2008. There are no long-term data on the impact of this practice on allograft survival or the development of chronic lung allograft dysfunction (CLAD). We extended our prior study to include long-term follow-up of 340 patients who received lung transplants between January 1, 2008 and December 31, 2011. We compared allograft survival and CLAD-free survival among patients in three cohorts: DSA-positive, panel reactive antibody (PRA)-positive/DSA-negative, and unsensitized at the time of transplant. The median follow-up time in this extension study was 6.7 years. Among DSA-positive, PRA-positive/DSA-negative, and unsensitized patients, the median allograft survival was 8.4, 7.9, and 5.8 years, respectively (p = .5908), and the median CLAD-free survival was 6.8, 7.3, and 5.7 years, respectively (p = .5448). This follow-up study confirms that long-term allograft survival and CLAD-free survival of patients who undergo DSA-positive lung transplants with the use of our protocol do not differ from other lung transplant recipients. Use of protocols such as ours, therefore, may improve access to transplant for sensitized candidates.

The practical integration of a hybrid model of ultrasound-guided peripheral venous access in a large apheresis center.

BACKGROUND: Apheresis treatments require adequate venous access using peripheral intravenous (PIV) catheterization or central venous catheters (CVC). Ultrasound-guided PIV (USGPIV) can be used to decrease the need of CVC insertions for apheresis procedures. METHOD: A hybrid model of USGPIV and standard of care (SOC) for PIV access was developed. Nurses performed USGPIV on all patients considered for PIV access if felt SOC PIV access was not possible. Information was collected regarding nurses' confidence with access, number of attempts required, site of access, complications, and need for CVC. RESULTS: In all, 226 PIV access attempts were made during a 2-month period. All apheresis procedure types were represented. A total 65% were accessed by SOC and 35% by USGPIV. USGPIV was successful on first try on 90% draw/inlet access and 87% successful on first try on return access. Access above the antecubital fossa was required in 31% of USGPIV for draw/inlet veins, and 22% of return veins. Nurses' confidence with accessing PIV was increased by USGPIV, based on 7-point Likert scale assessments. During the recording period, 2/226 (0.9%) apheresis procedures required a CVC. In a separate cohort of only hematopoietic progenitor cell collections, CVC insertion was required in 44/238 (18.5%) patients, in 7 months prior to adoption of USGPIV and 5/152 (3.3%) patients in 7 months following adoption of USGPIV. CONCLUSION: A hybrid model of using SOC and USGPIV for PIV access for apheresis procedures resulted in decreased need for CVC access, high levels of successful initial access attempts, and increased nursing confidence in PIV access.

Peripheral vascular access for therapeutic plasma exchange: A practical approach to increased utilization and selecting the most appropriate vascular access.

BACKGROUND: Therapeutic plasma exchange (TPE) is used in the treatment of many diseases. At present, peripheral vascular access (PVA) is an underutilized method of vascular access in TPE. It should be considered more frequently due its relatively low risk for adverse events, particularly infections. METHODS: The Advancing Vascular Access in Apheresis Working Group met in December 2017 for an extensive review and discussion of vascular access for TPE and developed a "road map" providing detailed information regarding clinical situations in which PVA-based TPE would and would not be appropriate. RESULTS: The road map is consistent with current recommendations that PVA should be used in combination with TPE whenever possible. PVA should be considered for patients who do not have existing central lines and who are stable. The patient should have peripheral veins that will allow for adequate treatment and must be able to comply with the process of achieving and maintaining peripheral access. There should be expert clinical assessment of veins, and this evaluation may include ultrasound and/or near infrared evaluation. Conditions that would prompt a switch from PVA to an alternate method of venous access include loss of venous access, patient preference, or development of a requirement for very frequent treatment over a long period of time. CONCLUSIONS: While PVA is not suitable for all patients requiring TPE, it has significant safety advantages over other approaches and should be employed whenever possible.

Preoperative Extracorporeal Membrane Oxygenation and Plasmapheresis for Urgent Pulmonary Endarterectomy in Heparin-Induced Thrombocytopenia-Positive Patient.

Pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. This case report outlines the importance of venoarterial extracorporeal membrane oxygenation and plasmapheresis as two important options in the management of heparin-induced thrombocytopenia-positive patients requiring urgent pulmonary endarterectomy.

Results of a cross Canada survey of blood film review practice patterns by technologists and pathologists.

INTRODUCTION: No common or widely accepted criteria exist for physician review of blood films or for reported standards of physician rate of blood film review. Individual institutions generally have internal criteria for physician review of blood films. To better understand how and why blood film reviews are performed at different institutions across Canada, with a specific interest in physician blood film review, we undertook a survey to assess the current practise patterns of physician review of blood films across Canada. METHODS: A 15 question survey was developed and sent to 24 academic, large community and corporate laboratories across Canada by e-mail to laboratory directors of those institutions. Centres were chosen to include all provinces in Canada and most of the major academic centres. Twenty of the 24 centres responded. RESULTS: The mean rate of physician review of blood films as a percentage of all CBCs processed per day was 4.1% (range 0.35%-13%) and of all blood films made per day was 28.8% (range 1.9%-66.5%). Data on factors which might affect physician review rates, physician preferences regarding what percentage of physician blood film review rates is reasonable and physician perspectives on the role of physician blood film review are discussed. CONCLUSION: This survey reveals that there is varying practise patterns and opinions with respect to blood film review by physicians in Canada.

Asymmetric Free-Space Light Transport at Nonlinear Metasurfaces.

Asymmetric light transport has significantly contributed to fundamental science and revolutionized advanced technology in various aspects such as unidirectional photonic devices, optical diodes, and isolators. While metasurfaces mold wave fronts at will with an ultrathin flat optical element, asymmetric transport of light cannot be fundamentally achieved by any linear system including linear metasurfaces. We report asymmetric transport of free-space light at nonlinear metasurfaces upon transmission and reflection. Moreover, we theoretically derive the nonlinear generalized Snell's laws that were experimentally confirmed by the anomalous nonlinear refraction and reflection. The asymmetric transport at optically thin nonlinear interfaces is revealed by the concept of a reversed propagation path. Such an asymmetric transport at metasurfaces opens a new paradigm for free-space ultrathin lightweight optical devices with one-way operation including unrivaled optical valves and diodes.

Safety and feasibility of red cell exchange for sickle cell disease across Canada.

We outline a case whereby RBCX was successfully provided over disparate geographical areas and time zones in Canada and overcame the logistical challenges of coordinating care across four different health care systems with the application of modern telecommunication technologies. We present this case as a model for other SCD providers and patients.

Cost-minimization analysis comparing intravenous immunoglobulin with plasma exchange in the management of patients with myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) exacerbations may be treated with intravenous immunoglobulin (IVIg) or plasma exchange (PLEX), which have equivalent effectiveness. This cost-minimization analysis compared IVIg with PLEX for treatment of patients with MG exacerbation. METHODS: We combined the Ontario-based health cost data with clinical data from a randomized clinical trial. Analyses were undertaken from the perspective of a public healthcare insurer and from the perspective of a tertiary university hospital payer. RESULTS: PLEX was less costly than IVIg among patients with a body mass index (BMI) > 15.7 kg/m(2) , from the perspective of the public healthcare insurer (P < 0.0001). However, PLEX was more costly than IVIg from the perspective of the hospital payer when the costs of blood products were excluded (P < 0.0001). CONCLUSIONS: PLEX can be considered a short-term cost-minimizing therapy when compared with IVIg for treatment of MG exacerbation among patients with BMI >15.7 kg/m(2) , from the perspective of a public healthcare insurer. Muscle Nerve 53: 872-876, 2016.

Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10-Color flow cytometry diagnosis and HyperCVAD therapy.

Few studies describe the comprehensive immunophenotypic pattern of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the bone marrow and its treatment. This retrospective analysis evaluates the diagnostic flow cytometry (FCM) pattern and outcome of nine patients diagnosed with BPDCN. A four-tube 10-color FCM panel used for diagnosis of acute leukemia (AL), showed cells in the blast gate (CD45dim/low SSC) and were positive for CD4(bright), CD33(dim), CD56(heterogenous), CD123(bright), CD36, CD38, HLA-DR, CD71. Seven patients received front-line induction therapy with HyperCVAD with an overall response rate of 86%. Five of six responders underwent planned allogeneic hematopoietic cell transplantation (allo-HCT). For a median follow up of 13.3 months, the 1-year disease free survival and overall survival were 56 and 67%, respectively. An accurate diagnosis of BPDCN can be made by 10-color FCM using a four-tube AL panel demonstrating a characteristic pattern of antigen expression. Front-line induction chemotherapy with HyperCVAD can yield high remission rates, but allo-HCT is required for long-term durable remissions.

Macroscale Transformation Optics Enabled by Photoelectrochemical Etching.

Photoelectrochemical etching of silicon can be used to form lateral refractive index gradients for transformation optical devices. This technique allows the fabrication of macroscale devices with large refractive index gradients. Patterned porous layers can also be lifted from the substrate and transferred to other materials, creating more possibilities for novel devices.

A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab.

The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician-diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital-based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow-up, one was a non-responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow-up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory-typical TTP in contrast to refractory-other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse.