Englewood Hospital and Medical Center

Importance: More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. Objective: To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Evidence Review: Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. Findings: It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). Conclusions and Relevance: Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

DESCRIPTION: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children. METHODS: These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

BACKGROUND: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. METHODS: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RECOMMENDATION 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

BACKGROUND: Blood utilization has long been suspected to consume more health care resources than previously reported. Incomplete accounting for blood costs has the potential to misdirect programmatic decision making by health care systems. Determining the cost of supplying patients with blood transfusions requires an in-depth examination of the complex array of activities surrounding the decision to transfuse. STUDY DESIGN AND METHODS: To accurately determine the cost of blood in a surgical population from a health system perspective, an activity-based costing (ABC) model was constructed. Tasks and resource consumption (materials, labor, third-party services, capital) related to blood administration were identified prospectively at two US and two European hospitals. Process frequency (i.e., usage) data were captured retrospectively from each hospital and used to populate the ABC model. RESULTS: All major process steps, staff, and consumables to provide red blood cell (RBC) transfusions to surgical patients, including usage frequencies, and direct and indirect overhead costs contributed to per-RBC-unit costs between $522 and $1183 (mean, $761 +/- $294). These exceed previously reported estimates and were 3.2- to 4.8-fold higher than blood product acquisition costs. Annual expenditures on blood and transfusion-related activities, limited to surgical patients, ranged from $1.62 to $6.03 million per hospital and were largely related to the transfusion rate. CONCLUSION: Applicable to various hospital practices, the ABC model confirms that blood costs have been underestimated and that they are geographically variable and identifies opportunities for cost containment. Studies to determine whether more stringent control of blood utilization improves health care utilization and quality, and further reduces costs, are warranted.

This prospective nonrandomized open-label cohort study addresses the safety and efficacy of exosomes (ExoFlo™) derived from allogeneic bone marrow mesenchymal stem cells as treatment for severe COVID-19. During April 2020, ExoFlo was provided to 24 SARS-CoV-2 polymerase chain reaction-positive patients at a single hospital center, all of whom met criteria for severe COVID-19 as well as moderate-to-severe acute respiratory distress syndrome. Patients received a single 15 mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy from days 1 to 14 post-treatment. All safety endpoints were met with no adverse events observed within 72 h of ExoFlo administration. A survival rate of 83% was observed. In total, 17 of 24 (71%) patients recovered, 3 of 24 (13%) patients remained critically ill though stable, and 4 of 24 (16%) patients expired for reasons unrelated to the treatment. Overall, after one treatment, patients' clinical status and oxygenation improved with an average pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) increase of 192% (P < 0.001). Laboratory values revealed significant improvements in absolute neutrophil count [mean reduction 32% (P value <0.001)] and lymphopenia with average CD3+, CD4+, and CD8+ lymphocyte counts increasing by 46% (P < 0.05), 45% (P < 0.05), and 46% (P < 0.001), respectively. Likewise, acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. In conclusion, owing to its safety profile, capacity to restore oxygenation, downregulate cytokine storm, and reconstitute immunity, ExoFlo is a promising therapeutic candidate for severe COVID-19. Future randomized controlled trials (RCTs) are needed to determine ExoFlo therapeutic potential.

PURPOSE: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS: Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

PURPOSE: To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy. METHODS: An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022. RESULTS: A total of 26 publications met eligibility criteria and form the evidentiary basis for the update. RECOMMENDATIONS: The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate.The Panel recommends the Practical Geriatric Assessment as one option for this purpose (https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf; https://youtu.be/jnaQIjOz2Dw; https://youtu.be/nZXtwaGh0Z0).Additional information is available at www.asco.org/supportive-care-guidelines.

Introduction Abbreviations used in this article: aCL, anticardiolipin antibodies, ANA, antinuclear antibodies, anti-dsDNA, anti-dsDNA antibodies, aPL, antiphospholipid antibodies, APS, antiphospholipid syndrome, ARDS, acute respiratory distress syndrome, CSF, cerebrospinal fluid, CT, computed tomography, DIC, disseminated intravascular coagulation, ECG, electrocardiogram, ENA, extractable nuclear antigen antibodies, ESR, erythrocyte sedimentation rate, HPF, high power field, INR, international normalized ratio, LA, lupus anticoagulant, PT, prothrombin time, PTT, partial thromboplastin time, SLE, systemic lupus erythematosus, TTP, thrombotic thrombocytopenic purpura, WBC, white blood count The antiphospholipid syndrome (APS), originally defined as the combination of venous or arterial thrombotic events, recurrent fetal loss, and, frequently, a moderate thrombocytopenia in association with antiphospholipid antibodies (aPL), was subsequently greatly expanded to include diverse conditions, for example, heart valve lesions, adrenal insufficiency, and pulmonary syndromes such as acute respiratory distress syndrome (ARDS), “capillaritis,” and pulmonary alveolar hemorrhage, among others (16,17). It was then realized that several “microangiopathic syndromes” also existed, as opposed to large vessel occlusive disease. Single organs, such as the kidneys, heart, skin, and brain, have been affected by this “thrombotic microangiopathy” in the context of the “classic” or “simple” APS. The temporal occurrence of thrombotic events in patients with this classic APS usually extends over months or years. In 1992, the existence of a new “subset” was described in which multiple vascular occlusive events, usually affecting small vessels supplying organs and presenting over a short period of time, were the outstanding features. This subset was termed the “catastrophic” APS. Although large vessel occlusions were also present, their prevalence did not in any way approach that in patients with the classic APS. The occlusions occurred over days to several weeks, and more than 50% of patients usually succumbed despite seemingly adequate therapy, including anticoagulation, steroids, etc. (6). In 1998, a comprehensive review article with the clinical and laboratory description of 50 such patients was published (8). In the present paper we describe the clinical and serologic features of the largest series of patients with catastrophic APS hitherto reported, including 30 new cases from interested physicians in many different countries, as well as a comprehensive literature review of 50 additional recently published case reports with this syndrome. This new series, comprising a total of 80 patients, enables us to analyze further and clarify not only the clinical importance of this syndrome, but also its pathogenesis. Methods We undertook a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of catastrophic APS published in English, Spanish, and French from 1996 (when the previous comprehensive review series of catastrophic APS was completed [8]) through 2000 (keywords:lupus anticoagulant, coagulation inhibitor, lupus inhibitor, anticardiolipin, cardiolipin, anticardiolipin antibody, antiphospholipid, phospholipid, antiphospholipid antibody, antiphospholipid syndrome, catastrophic antiphospholipid syndrome). We also retrospectively analyzed several original cases categorized as having catastrophic APS that were not included in the previous series. Additionally, the bibliographies of all articles were systematically scanned for references not identified in the initial search. Patients were considered as having catastrophic APS if they presented an acutely devastating APS with multiple organ involvement, as previously defined (6). Data from these patients were summarized using a standardized data form, including sex, age, diagnosis of the underlying condition, precipitating factors, main thrombotic clinical manifestations, immunologic features, treatment, and evolution. Thirty new and previously unpublished cases (14 patients from the European Union, 8 from the United States, and 8 from other countries) were added to the literature review. The bilateral Fisher exact test was used for statistics. Case Reports The most relevant data of the 80 case reports described in clinical and and case reports described in clinical of 80 patients with catastrophic clinical of patients the of catastrophic of patients with catastrophic The was a with of and systemic lupus in presented with and included antinuclear antibodies anti-dsDNA, and antibodies and lupus were not a with and an of syndrome in which to was well of a In of and small bilateral and a The was the blood and were and the anti-dsDNA antibodies were was as for a lupus was with and was The heart was and blood was was was bilateral the were and the were but The was but not were and was blood prothrombin partial thromboplastin and were all were but were were but and were a heart and were the and a with The pulmonary was of the of small a and the of but lupus and with thrombotic was was for days by was also with of were also for the all the of the arterial the and was bilateral was and was to the with the of the that the was the In was by was the with the of a which The the and were of of the of a of the with The of the small the the the was with and the the and of were and the were and with and syndrome from bilateral to over the and and with The was to with white count to with and disseminated intravascular coagulation to and as well as succumbed to The subsequently APS in a with a previous of as a lupus but the of in this syndrome to and not to Case This with presented with and been for an respiratory did not any to in acute and was white blood count was was count was was was was and was was of and a in the of the small acute the and thrombotic was with and with and to was then and was a with or with 50% and 50% and of with of as well as to of in and was the clinical was by and but only of did not any further in The was and an of and an of The were of the small acute the and respiratory catastrophic APS in a with Case was in of and for been as having with as well as valve The erythrocyte sedimentation was was but were and were were anti-dsDNA antibodies was of with was of months this was and well the of the was a in the and valve the count and blood power as well as was for was with was as was were in the was anti-dsDNA antibodies were and antibodies were was diagnosis of was and the of and with bilateral multiple pulmonary with pulmonary and pulmonary The heart was with a was diagnosis of APS the of was and the was of and the clinical The with of only were also an and The was to the a days of and precipitating for the of catastrophic APS. Case was in 1996 with and days a of The diagnosis of been in and been with In months to a was and was that time, was the a in with thrombocytopenia was and anti-dsDNA, and antibodies were The of was to and was was months was to the of bilateral in and and thrombocytopenia were was by and was vascular in the of the of a diagnosis of APS to was was 50 and was In and the was and were and was well the of the present and in and as well as in the was was a and was with a of blood was and was and an of with a of of and count of of and and were and were and with was anti-dsDNA antibodies and were was and of pulmonary In the a of pulmonary was of the with in the of the and and The of a was The heart were and of was diagnosis of to pulmonary the of with APS was and The was and to of therapy, and and In a days of and the and in the pulmonary with a The of was was by and other were in the of the the of an with partial in the and its the of the with was and pulmonary and Although of small vessels the of catastrophic APS, large vessels Case was in with and days previously the of as well as the In a diagnosis of been been with the been many to of In of and was and anti-dsDNA antibodies were was with and the of these presented with lesions, and In the diagnosis of APS in the of was of venous in the of and antibodies was with the acute and The of from 30 to 80 was and with in and were blood was with an of and of and and were and was was and anti-dsDNA antibodies were was and were were were were The multiple in diagnosis of pulmonary was but pulmonary not 80 of and and this and The from to and in and of clinical and the was to the was and the of was the to respiratory and features of in the of catastrophic APS. Case was in of in and the been for In was of acute of was with valve and valve insufficiency, heart and bilateral in the with The laboratory of and of The was not and were and was The blood was of and were and pulmonary The in the pulmonary was 30 an of with and was for and were and was anti-dsDNA antibodies were was antibodies were high were was The of was diagnosis of APS was and was of was and bilateral the which but the the diagnosis of was of and to the with and therapy, days and and of a in the of catastrophic APS and a of Case The was a with a of and APS with insufficiency, and was to but was to the venous was of the and of the a of of count of of and of and a The was for of by heart was with and was of and venous was for venous The was also to have and of of an of and of The to and was was then to have antibodies in to aCL, and a in blood and were for of to that was not to of the and were the and was with for the to and was to have and was for of and to the that and a new was was and the was with with of the was was to and an of was for and with were a to and were was to have the a and was of the was for a a in blood to new The count and was to The were which several days The and to for the of the were to but than the an acute in and that a to and was with but to to and with a blood of was with a small It was to including but new The 80 days multiple small and vessel in different of were multiple organs Although catastrophic APS also in patients with other than or APS Case 8 This was a of but was or with an of the with arterial and venous pulmonary and of the and of the was with and with and which to The cerebrospinal of were was by of and a and acute also were present the of and were and all for and including and were was for diagnosis of catastrophic APS was and the was therapy, with and In of treatment, clinical was added the of total of was over was the and by the and of occurred by the was the to and an of of was the normalized was The clinical of the was over the for the was the with of the and of the precipitating for catastrophic APS. Case The a a of of and from and presented with acute and to have a and moderate thrombocytopenia which to was respiratory occurred and a of the the with a of were with of were blood The was and were of count was ANA, anti-dsDNA, nuclear antigen antibodies and were was The was and then and was was to of the The was with and and with the with of the was of and and been with of the valve with and of blood of patients with catastrophic APS. Case The was a with a of the of in of and the was to have blood and of the and power was thrombocytopenia The was 8 and 8 The was and the of and The was anti-dsDNA antibodies were and and were The a diagnosis of was and to the was that count to and was the of and was The blood and was with a of was with thrombotic was and of a and blood were for to the was of and was then with and was was then of the with The were was and was for the the to and of were was for was for APS and by were an and was blood the was by an in to with and the other of was of of The of that to the of was with multiple were and for syndrome and a precipitating the presenting of catastrophic APS. Case of for and was in a of by pulmonary in 1996 a and was as having APS with for and as well as was with and was to a in for a a were a of a respiratory of and blood to by was was and was present over the was a The was and were the and were and of was with 50 50 a with of with a heart The was with the the were The main were and were The and were the The was not and were The a short the of the This was to to in the of clinical of of the The of the was small of was the The and features. diagnosis of to APS was and was the of was by The was over the and The was not but were venous was the not to the and were to but were with to the The was also the main was to It with The a that they were with in the Although the not with a small venous was in the of the The was in The was not well The of the main and were with previous but were The and were were and the were in was and the a main pulmonary was the of a was and a of of and blood was The a heart a large in the pulmonary and and an of in the of the was to the and was subsequently to to acute pulmonary was with by The of was considered but of high was by acute to acute or but was to have a of the of and was of through a was days and was of the was and with days of and well the precipitating of catastrophic APS. Case presented to the in was by the and was with and The was small for and the subsequently an a days a of a in been that an vessel that did not with was also to have valve the of in a of and and a and a with a anti-dsDNA antibodies a of and a of also by a and a a was in and of a small for with large of that from to by vascular The was with and for the was and to well for with and then and was subsequently with of and with of a This and an in a This an of the was was for and then and was and was The was for a months and then from for of of this also In 1998, presented with an of as an and a a and with of was but several of to the was and was but of this a of and of and an of The was and the was this acute the the only to a a of the a with multiple and multiple in the It was that the have a and a of the of the occlusive of in the with of these of was in the of the of the with been but these reports was that The to well of and and a lupus the precipitating of catastrophic APS. of the series of patients in the 80 patients were and were ratio, with from to from defined SLE, from APS, from from systemic and and than patients from and from of 80 patients with catastrophic and of APS were present in were with pulmonary recurrent fetal and previous were and arterial thrombotic syndrome, heart valve lesions, and of the precipitating of catastrophic APS that the most in more than of the patients was from respiratory to and other conditions, such as and such as in 80 patients with catastrophic most precipitating was and from a to and other association with was in of the of or to of the cases of catastrophic APS. association was with such as or the syndrome. were with or to The clinical of catastrophic APS was usually several the most the of the were and of catastrophic APS in 80 the clinical to thrombotic events the of catastrophic APS. patients catastrophic APS. total of of catastrophic APS of catastrophic was identified in of and adrenal were in of and pulmonary but involvement, and or valve lesions, but of but or venous and venous were present in and arterial occlusive by occurred in were also and of purpura, of small and lesions, and multiple were and and The laboratory of the 80 patients of this series in count than was in patients, of in of with laboratory features of and prothrombin and in and small of was blood in and immunologic features in 80 patients with catastrophic was in of the patients in which this test was The was in of patients patients presented high of of the The were in of patients usually in The anti-dsDNA antibodies were in of the patients with defined SLE, but in of the patients with other The of was in of and the 80 patients, In most patients, to the of to acute heart and was also present in several of of catastrophic APS was considered including in the patients Data were not for 80 of catastrophic APS were analyzed occurred in of and in by was the most treatment, used in of 80 in high were used in in in and in patients, a combination of the or of a treatment, occurred in of with in were not in of with in were not in of with in were not in of with in were not and in of with in were not diverse occurred in of with in were not in of with anticoagulation, steroids, and of with anticoagulation, steroids, and and of with anticoagulation, steroids, and or for of 80 of catastrophic The “catastrophic” APS was in to describe the clinical of a subset of patients with APS (6). patients of small vessels affecting multiple organs such as the heart, brain, adrenal or in of the 80 patients presented these additional several clinical example, ARDS, adrenal and from the present series. the pulmonary of catastrophic APS and in patients with APS. It a of pulmonary that from acute to the In previous been that the with by the or by with or to a of the The of such as in that a been to in and this to catastrophic APS patients with this in the of the that in the systemic syndrome which by affecting the vascular and by and in to and also of and In of systemic syndrome, antibodies also The of adrenal in catastrophic APS to as with this in patients with APS. It also more than of the venous for example, their from the The for this and to in and the have over the case in which this in patients with APS been The adrenal with of the syndrome in patients with catastrophic the diagnosis include other of a presenting in these or more than and of importance its occurrence pulmonary the of a as a further The for of adrenal and the of more adrenal also described in patients in association with as been by and patients have a of in the many which have the of APS. The of that of adrenal venous bilateral which to of the and of the arterial in adrenal been in several patients with other coagulation for example, with and and also as a of any underlying coagulation was the of cases with as opposed to than patients from the present series this a condition, most in patients with acute or and this added catastrophic APS. in the association APS and in a this the The occurrence of this days been by This a previous of recurrent and occurrence in was by in in a with a of a and high of in this with and In the literature with APS patients reported, of from catastrophic APS. It among the well of the in catastrophic APS patients for the present catastrophic APS most as opposed to patients with thrombotic thrombocytopenic this not patients in series presented the of their The described by and a presented with pulmonary and adrenal as well as features of but a further of catastrophic APS a pulmonary therapy, and also and by was a with of catastrophic APS only to months from a pulmonary the The affected the and in the not only were but also the clinical respiratory the and patients with this “catastrophic” others present with the “classic” APS. the present comprehensive review of the clinical of 80 patients we the of this APS, a to have a to in other were in such as example, serologic for have been in a of from and to and example, and of the to of the in that their to not this not not that in a the or or other the the of the the and the of the from the of the of by with or the of the fetal and to a in and in This also the of in by with and their the the of by with with and APS in this and APS by a series of additional a they identified that with the the of the antibodies and the in and of APS in the they a high of the with different and were with a of the with the the to the relevant to was from the were and the of clinical was the with antibodies from with or with to the the of clinical which APS. The that the of by and included in with of the that many diverse and in these catastrophic APS. We as in which the and the in the the of the and The of that these to the in patients with catastrophic APS. It to more with in patients with APS and to these patients also to the of the of events in catastrophic APS with by as well as other then of the including for the of as well as of the The of the to of of aPL, the of and The then the coagulation which in the of to also a for and in this also by of which in the and of of to the to which also of The also to and an and have been to The for catastrophic APS was a in the of It also that in the and a to the catastrophic of the disease. for example, a precipitating for catastrophic APS to factors, and the of also the for the association of catastrophic APS with example, such as or for to days to by recurrent and cases of catastrophic APS have been these also to its a in patients with APS for or if of the high of with coagulation The association of with the of catastrophic APS, which to a 50% the The by in the of this in the patients as with termed “thrombotic were of catastrophic APS, and, were not in the that these were also of the that the in patients with to then by the in to as and coagulation prothrombin and and a in the such as and and also The case by patients catastrophic APS that of the affected by to the and catastrophic APS. It been that large of in of patients with TTP, and these in the of to vascular a these large It been that this in patients with and that an to the for its in patients with a more of by a acute The existence of these large of not been in patients with catastrophic APS not been in of have not been In patients catastrophic APS, several or of this patients an with a and to the and then have to a of several in a to of this have been in the present review. It not that in the cases in which APS was to SLE, the of the catastrophic was to an these with an and the existence of an of also the In cases in which a precipitating not the to a or to as that to the It well in any with APS, an underlying the example, a small or only a The that with catastrophic APS and the patients included the of this The of in to in patients with and several have been in the pathogenesis. have been to in to of patients and also been that a inhibitor, which by and a blood coagulation have been to such as have been to with of have been to with and, patients have the of in this of patients, but also other The in patients with to patients have The of catastrophic APS in the present series was to that in the from 50% to these data considered an the with the of considered as to in a acute thrombotic did not in series and of catastrophic APS did not include in of in the present series in the physicians were of its in and thrombocytopenic patients, presenting with to that the with the of from from the and the present series for a of we a of in patients with in its In additional the of a of to for the (8). we that in association with anticoagulation, as a in to the in catastrophic APS and, a which catastrophic APS in patients with also of but their not to to in catastrophic APS. Additionally, and of in case of in of the of patients in to the of catastrophic APS include and of precipitating in this and We analyzed the clinical and laboratory of 80 patients with catastrophic antiphospholipid syndrome new cases and 50 from a computer-assisted review of the literature from 1996 through from defined systemic lupus from APS, from syndrome, from systemic and and of patients in this series was The most precipitating were and and of or international normalized The of the acute was usually multiple organs or in a short The of patients occlusive vascular affecting small vessels or organs, brain, heart, and a of patients large vessel was in patients, in disseminated intravascular coagulation in and in The antibodies were anticardiolipin antibodies lupus of patients with antinuclear antibodies and was used in of the in in in and in patients, a combination of occurred in of the 80 In to the of In several of respiratory was also present, usually to acute respiratory distress syndrome and alveolar occurred in of with in were not and in of with in were not other combination was with a in The and for us their patients with catastrophic antiphospholipid syndrome.

BLOOD management has been defined as “the appropriate use of blood and blood components, with a goal of minimizing their use.”‡This goal has been motivated historically by (1) known blood risks; (2) unknown blood risks; (3) preservation of the national blood inventory; and (4) constraints from escalating costs.1Known risks of blood include transmissible infectious disease, transfusion reactions, and potential effects of immunomodulation (e.g. , postoperative infection or tumor progression). Unknown risks include emerging pathogens transmissible by blood (e.g. , new variant Creutzfeldt-Jakob disease and West Nile virus).2–4In addition, several studies have linked allogeneic blood transfusions with occurrence of unfavorable outcomes including increased risk of mortality and various morbidities.5–7For example, studies have indicated that the risk of postoperative infections such as sepsis are as much as two to four times higher in transfused patients compared with untransfused cohorts.8–9Taken together, these lines of evidence support the implementation of blood management as a means to improve the clinical outcomes of the patients. Blood management was cited recently as 1 of the 10 key advances in transfusion medicine over the past 50 yr.10Patient-focused blood management11is described in the Circular of Information§as “a professional judgment based on clinical evaluation that determines the selection of components, dosage, rate of administration…..” Patient blood management therefore encompasses an evidence-based medical and surgical approach that is multidisciplinary (transfusion medicine specialists, surgeons, anesthesiologists, and critical care specialists) and multiprofessional (physicians, nurses, pump technologists and pharmacists). Preventive strategies are emphasized to identify, evaluate, and manage anemia12–14(e.g. , pharmacologic therapy15and reduced iatrogenic blood losses from diagnostic testing)16; to optimize hemostasis (e.g. , pharmacologic therapy17and point of care testing18); and to establish decision thresholds (e.g. , guidelines) for the appropriate administration of blood therapy.5,19Patient blood management has recently been recognized by the World Health Organization (World Health Alliance Resolution A63.R12) as a means to “promote the availability of transfusion alternatives.”‖To achieve these goals, health care institutions and accreditation and regulatory agencies have focused on blood utilization to improve clinical outcomes and patient safety. In the United States, The Joint Commission developed Patient Blood Management Performance Measures and submitted these to the National Quality Forum for endorsement. The National Quality Forum did not endorse these submitted Performance Measures, citing lack of data on the outcomes proposed; as a result, they currently do not carry consequences if not met. Because these Performance Measures were process-based rather than outcomes-based, data on proposed outcomes are difficult to retrieve. The Joint Commission has placed these Performance Measures in their Topic Library where they are to be used as additional patient safety activities and/or quality improvement projects by provider institutions as accreditation goals.#The principles of these performance indicators are summarized in table 1. We review recent advances in patient blood management to identify for physicians and healthcare institutions opportunities for process improvement blood utilization and patient safety.Guidelines for detection, evaluation, and management of anemia in elective surgery patients have been published (fig. 1).12,13Predictors of blood transfusion for patients have long been identified, with the most important being the preoperative circulating erythrocyte mass,20as estimated by the patient's hemoglobin concentration. In addition to being a risk factor for blood transfusions, preoperative anemia is also an independent predictor of morbidity and mortality postoperatively.21–24Evaluation of anemia**should begin with an initial assessment of iron-restricted erythropoiesis, which can occur in either the presence or absence of inflammation. Absorption of oral iron is inhibited in the presence of hepcidin due to inflammation, whereas chronic blood loss (e.g. , menses) is an important cause of iron deficiency in the absence of inflammation.25,26Iron-restricted erythropoiesis can cause anemia due to an absolute deficiency of storage iron, an iron sequestration syndrome due to inflammation, or a functional iron deficiency due to erythropoietin-stimulated erythropoiesis.27The evaluation of unexpected anemia must in addition consider unexpected diagnoses including chronic kidney disease or occult malignancy. To facilitate this, screening and detection of anemia should occur as far as possible in advance (up to 30 days) of an electively scheduled surgery.13,28This requires close collaboration among the patients' primary care physicians, surgeons, anesthesiologists, and the medical directors of the institution's preadmission testing program.Successful completion of diagnostic testing pretransfusion (blood type/screen crossmatch) must overcome barriers associated with changes in practices for patients undergoing elective surgeries and for the availability of cross-matched blood. A College of American Pathology survey found that 35% of approximately 9,000 patients had type/screen specimens collected only on day of surgery; one-fourth of these tests were not completed (and cross-matched blood was not available) until after surgery had begun.29To address these barriers, we implemented a number of steps for process improvement at one of our own institutions30: After implementation, the incidence of patients undergoing surgery before availability of cross-matched blood was reduced from 1:133 to 1:328. A compliance rate of 100% for the surgical checklist is necessary to achieve our goal in which no patient undergoes elective surgery without cross-matched blood available.Documentation of transfusion events including informed consent are the Performance Measures specified by The Joint Commission: In addition, The Joint Commission Performance Measures specify that appropriate pretransfusion laboratory testing (e.g. , hemoglobin, prothrombin time/international normalized ration (INR), and platelet count) be documented along with the clinical indications (see next paragraphs) for transfusion of blood components. Adherence to such requirements should be monitored by the hospital's quality department or transfusion committee.The elements of transfusion consent comprise a discussion of blood transfusion risks (table 2)2,3and benefits; alternatives to blood; an opportunity to ask questions; and patient consent.32Current estimates of risk of blood transmission for some known viruses are: 1:280,000 to 1:357,000 for hepatitis B; 1:1,149,000 for hepatitis C; and 1:1,467,000 for human immunodeficiency virus (HIV).32,33Consent should occur as far in advance of transfusion as possible, so that alternatives to allogeneic blood such as autologous blood can be made available. As an example, California Health and Safety Code Section 1645 (Paul Gann Blood Safety Act) mandates that alternatives to allogeneic blood are made available for patients and “applies whenever there is a reasonable possibility that a blood transfusion may be necessary as a result of a medical or surgical procedure.” It should also be noted that blood transfusion has been legislated to be a medical service not subject to commerce and trade laws, thus excluding the principle of implied warranty and granting blood banks immunity from strict product liability.34When feasible, the patient's own (autologous) blood can serve to reduce or eliminate the need for allogeneic blood. In preoperative autologous donation, the patients donate their own blood over a period of a few weeks preceding the elective procedure.35In acute normovolemic hemodilution, the donation takes place in the operating room before the surgery and reinfusion occurs before the patient leaves the operating room. In cell salvage, the reinfusion occurs during or after the surgery as patients' blood is collected and reinfused.Preoperative autologous donation has some limitations.15As with allogeneic blood units, autologous blood is susceptible to acquired storage lesions, such as depletion of 2,3-diphosphoglycerate and impaired ability for erythrocytes to unload oxygen to tissues. Many predonated blood units may be wasted rather than transfused. In addition, preoperative autologous donation induces anemia preoperatively, with an attendant increased subsequent likelihood of blood transfusion with the associated risks, including errors in blood administration. Thus, preoperative autologous donation is generally not cost-effective but may be of value in selected patient populations, such as in patients previously alloimmunized with erythrocyte antibodies.36Acute normovolemic hemodilution causes blood losses during surgery to be diluted, thus reducing actual total blood losses. Acute normovolemic hemodilution offers several advantages compared with preoperative autologous donation, including avoidance of blood storage lesions; no risk of blood labeling or patient identification errors; and adaptability for patients undergoing nonelective procedures.37However, evidence on efficacy of acute normovolemic hemodilution is mixed.38–40Reasons for low acceptance include lack of standardized protocols, variations in the target hemoglobin, types of fluids used, heterogeneity in surgical blood losses by procedure, and patient selection criteria. Acute normovolemic hemodilution is most effective in procedures associated with large blood loss. Publications addressing the efficacy of acute normovolemic hemodilution have used mathematical modeling that does not take into account individual patient vascular and hemostatic compensation. Because some large blood loss surgical procedures may not result in significant blood loss, benefit of acute normovolemic hemodilution may not be realized. Regardless, the risk of monitored acute normovolemic hemodilution is extremely low and this rare loss of benefit still favors acute normovolemic hemodilution.41Autologous blood cell salvage and reinfusion has been demonstrated to be safe and effective in reducing allogeneic blood transfusions in a variety of patient populations.42,43The procedure requires the collected shed blood to be washed, resulting in loss of platelets and plasma, which could potentially cause dilutional coagulopathy or thrombocytopenia with large blood volumes processed. However, reinfusion of the yielded autologous blood is still preferred rather than allowing the shed blood to be completely wasted, or using allogeneic blood that is also devoid of platelets and plasma and carries the same if not more risks at large volumes. The use of cell salvage in situations such as cancer and obstetric and bowel (contaminated) surgeries with introduction of unwanted materials into the circulation has been considered a relative contraindication for cell salvage44; nevertheless, this technique has been used successfully in these circumstances.45AABB has Standards for Perioperative Autologous Blood Collection and Administration46to provide guidance on quality management for facilities who seek accreditation for these activities.Of the estimated 39 million discharges in the United States in 2004, 5.8% (2.3 million) were associated with blood transfusion.47Blood transfusion occurred in more than 10% of all hospital stays that included a procedure and was the most frequently performed procedure in 2009. The rate of blood transfusion more than doubled from 1997 to 2009.‡‡Increased provider awareness of the costs associated with blood transfusion4and recognition of the potential negative outcomes have stimulated multidisciplinary, multiprofessional, and institution-based approaches to patient blood management. For the 4-yr period 2005–2008, 212 fatalities reported to the Food and Drug Administration48were deemed to be transfusion related (fig. 2); the leading causes of death were transfusion-related acute lung injury (n = 114), hemolytic transfusion reactions (n = 46), transfusion-associated sepsis (n = 18), transfusion-associated cardiac overload (n = 17), and babesios (n = 10). As discussed previously, a greater number of patients could have potentially had worse clinical outcomes (increased morbidity and mortality) associated with unnecessary transfusions in the same period.Guidelines for blood transfusion attest to the inadequacy of discrete hemoglobin concentrations as ‘triggers’ for transfusion, and in addition to recommending transfusion of one blood unit each treatment event, they also acknowledge the necessity of considering other more physiologic criteria.49It is generally agreed that transfusion is not of benefit when hemoglobin concentrations are greater than 10 g/dl, and are beneficial when hemoglobin concentrations are less that 6 g/dl.50,51The variability in transfusion outcomes in patients undergoing cardiothoracic surgery continues to persist even after adjusting for patient- and institution-related factors.52,53Moreover, prospective randomized trials in patients undergoing cardiac54and noncardiac55,56surgery have each demonstrated that such patients can tolerate perioperative anemia without transfusion to hemoglobin concentrations between 7 and 8 g/dl, and have equivalent clinical outcomes comparable with transfusions to hemoglobin concentrations of greater than 10 g/dl. It is noteworthy that the recently published FOCUS trial found that elderly (mean age older than 80 yr), high-risk (factors for coronary artery disease) patients who have undergone hip fracture surgery tolerate a hemoglobin trigger as low as 8 g/dl (or higher if symptomatic).56A Cochrane meta-analysis of prospective randomized trials57comparing “high”versus “low” hemoglobin thresholds on more than 3,700 patients found that (1) “low” hemoglobin thresholds were well tolerated; (2) erythrocyte transfusions were reduced (approximately 37%) significantly in patients randomized to the “low” hemoglobin cohorts; (3) infections were reduced by 34% in patients in the “low” hemoglobin cohorts; and (4) a hemoglobin concentration of 7g/dl was sufficient for most patients. More recently, a randomized controlled trial of 2,016 elderly patients with history or risk factors of cardiovascular disease who underwent hip surgery demonstrated that mortality rates, inability to walk independently, and in-hospital morbidity rates were similar in liberal- versus restrictive-transfused patients, despite significant fewer transfusions in the restrictive group.56Patient blood management strategies for patients undergoing cardiac surgery have been shown to be safe and effective in reducing transfusion, while at the same time delivering high-quality outcomes. One of our institutions58reported that only 11% of patients undergoing cardiac surgeries received blood transfusions, in which the program ranked first in their state for lowest risk-adjusted mortality. Other single-center initiatives using laboratory-guided transfusion algorithms in both operating rooms and intensive care units have reported a 50% reduction in transfusions of blood components (personal communication, September 9, 2011, by Mark Ereth M.D., Professor of Anesthesiology, in the Department of Anesthesiology at the Mayo Clinic in Rochester, Minnesota, as presented at the Mayo Clinic Symposium (February 2011) on Patient Blood Management). Both the pediatric59and adult hospitals at one of our own medical centers have reduced blood utilization using computerized physician order entry: hemoglobin threshold for blood transfusion decreased in our adult hospital after a clinical effectiveness team instituted physician education and clinical decision support via electronic physician order entry (fig. 3).Data from the American Red Cross on blood usage suggests an estimated decline of 3% over each of the past 2 yr (2009–2010), indicating that physician behavior toward blood transfusions is undergoing change nationally (personal communication, September 9, 2011, Richard Benjamin M.D., Ph.D., Adjunct Associate Professor of Pathology at Georgetown University, Washington, D.C., and Chief Medical Officer for the American Red Cross; as presented at the Food and Drug Administration Blood Products Advisory Committee, June 2011). This trend is accompanied by data from the most recent National Blood Collection and Utilization Survey,§§which shows a progressive annual decrease in number of patients and percentage of hospitals who have cancelled elective surgical procedures due to blood inventory constraints (table 3). Current initiatives in research for blood transfusions are reflected in the growing literature on adverse effects of blood storage and their possible implications for oxygen delivery by blood transfusion.60In a recent evidence-based review the Transfusion Practices Committee of the AABB recommended plasma therapy for only a few clinical indications, based on the available evidence in the literature (which was assessed to be of “weak quality”): trauma patients with substantial hemorrhage, patients undergoing complex cardiovascular surgery, and in patients with intracranial hemorrhage requiring emergency reversal of warfarin-associated coagulopathy.61Patients with mild prolongations of the INR (less than 1.7) are not at risk of bleeding and do not need plasma therapy for minor procedures,62so that for most clinical settings there is ample evidence that plasma transfusions are inappropriate. However, logistical/technical barriers that prevent effective and timely plasma therapy (possibly resulting in plasma therapies that are “too little, too late”) have probably contributed to the paucity of evidence demonstrating any benefit for plasma therapy.17One of the largest prospective studies63of plasma transfusions and their effect on INR and bleeding included both medical and surgical patients with pretransfusion INR of between 1.1 and 1.85. The authors reported that less than 1% of patients had normalization of their INR and only 15% had at least 50% correction. The median dose of plasma was 2 units (only 5 to 7 ml/kg), and there was no correlation between plasma dose and change in INR. This study had many of the limitations common to other reports64in this clinical arena: lack of control groups, only modest prolongation in coagulation tests, poorly defined clinical endpoints (e.g. , change in hemoglobin or need for transfusion), and/or an inadequate dose of plasma therapy.The paucity of evidence for benefit of plasma transfusion therapy has been accompanied by growing evidence that risks of plasma have been underrecognized; in a prospective study, 6% of transfused patients developed transfusion associated cardiac overload65which is much higher than previously reported rates in retrospective studies.66,67Transfusion-related acute lung injury68is a significant cause of morbidity/mortality from blood transfusions, whose incidence has with use of plasma from or who have no history of performance for platelet transfusions has been developed by The Joint Commission for patients with or who cell in which a platelet threshold of appropriate for platelet from the and United States a transfusion trigger of 10 for platelets transfused are based on outcomes from four randomized clinical trials that compared of 10 versus in patients with acute and in autologous and allogeneic cell additional prospective studies also demonstrated safety with the threshold of 10 for platelet effect of these thresholds on of platelet and blood transfusions is one study demonstrated a and reduction in platelet and blood transfusions, no recent that platelet transfusions are effective as with or For platelet transfusions, algorithms for platelet transfusions based on point of care testing have demonstrated in patients who have bleeding such as in cardiothoracic in for the evidence-based literature for plasma additional studies in platelet transfusion are also transfusions carry risks, are and the of blood is Blood transfusion outcomes are therefore undergoing by healthcare institutions to reduce blood In addition to accreditation professional are also well to blood transfusion outcomes as quality indicators in their own and improvement in health care has been described as undergoing an in which in outcomes between quality and safety are this has been by a of from quality to process and safety to value or between quality and safety has been for patients in transfusion patient blood management patient safety by reducing blood Medical from errors in patient identification and labeling in blood currently known risks from that the is to to result in for patients who transfusions In recognition of this the Department of Health has the of a national to establish for blood of patient blood management in the period are in (1) optimize (2) blood and (3) manage begin with preoperative preadmission testing and the and the postoperative physicians to allogeneic blood transfusions, while delivering safe and effective and hospital effectiveness should principles of patient blood management into process improvement initiatives that improve patient safety and clinical outcomes.

BACKGROUND: Pressure ulcers are one of the most underrated conditions in critically ill patients. Despite the introduction of clinical practice guidelines and advances in medical technology, the prevalence of pressure ulcers in hospitalized patients continues to escalate. Currently, consensus is lacking on the most important risk factors for pressure ulcers in critically ill patients, and no risk assessment scale exclusively for pressure ulcers in these patients is available. OBJECTIVE: To determine which risk factors are most predictive of pressure ulcers in adult critical care patients. Risk factors investigated included total score on the Braden Scale, mobility, activity, sensory perception, moisture, friction/shear, nutrition, age, blood pressure, length of stay in the intensive care unit, score on the Acute Physiology and Chronic Health Evaluation II, vasopressor administration, and comorbid conditions. METHODS: A retrospective, correlational design was used to examine 347 patients admitted to a medical-surgical intensive care unit from October 2008 through May 2009. RESULTS: According to direct logistic regression analyses, age, length of stay, mobility, friction/shear, norepinephrine infusion, and cardiovascular disease explained a major part of the variance in pressure ulcers. CONCLUSION: Current risk assessment scales for development of pressure ulcers may not include risk factors common in critically ill adults. Development of a risk assessment model for pressure ulcers in these patients is warranted and could be the foundation for development of a risk assessment tool.

IMPORTANCE: Postoperative delirium occurs in 10% to 60% of elderly patients having major surgery and is associated with longer hospital stays, increased hospital costs, and 1-year mortality. Emerging literature suggests that dexmedetomidine sedation in critical care units is associated with reduced incidence of delirium. However, intraoperative use of dexmedetomidine for prevention of delirium has not been well studied. OBJECTIVE: To evaluate whether an intraoperative infusion of dexmedetomidine reduces postoperative delirium. DESIGN, SETTING, AND PARTICIPANTS: This study was a multicenter, double-blind, randomized, placebo-controlled trial that randomly assigned patients to dexmedetomidine or saline placebo infused during surgery and for 2 hours in the recovery room. Patients were assessed daily for postoperative delirium (primary outcome) and secondarily for postoperative cognitive decline. Participants were elderly (>68 years) patients undergoing major elective noncardiac surgery. The study dates were February 2008 to May 2014. INTERVENTIONS: Dexmedetomidine infusion (0.5 µg/kg/h) during surgery and up to 2 hours in the recovery room. MAIN OUTCOMES AND MEASURES: The primary hypothesis tested was that intraoperative dexmedetomidine administration would reduce postoperative delirium. Secondarily, the study examined the correlation between dexmedetomidine use and postoperative cognitive change. RESULTS: In total, 404 patients were randomized; 390 completed in-hospital delirium assessments (median [interquartile range] age, 74.0 [71.0-78.0] years; 51.3% [200 of 390] female). There was no difference in postoperative delirium between the dexmedetomidine and placebo groups (12.2% [23 of 189] vs 11.4% [23 of 201], P = .94). After adjustment for age and educational level, there was no difference in the postoperative cognitive performance between treatment groups at 3 months and 6 months. Adverse events were comparably distributed in the treatment groups. CONCLUSIONS AND RELEVANCE: Intraoperative dexmedetomidine does not prevent postoperative delirium. The reduction in delirium previously demonstrated in numerous surgical intensive care unit studies was not observed, which underscores the importance of timing when administering the drug to prevent delirium. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00561678.

BACKGROUND: There is little systematically derived evidence-based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice guidelines to help direct appropriate transfusion of plasma. STUDY DESIGN AND METHODS: A systematic review (SR) and meta-analysis of randomized and observational studies was performed to quantify known benefits and harms of plasma transfusion in common clinical scenarios (see accompanying article). A multidisciplinary guidelines panel then used the SR and the GRADE methodology to develop evidence-based plasma transfusion guidelines as well as identify areas for future investigation. RESULTS: Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy-related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients. CONCLUSION: We have systematically developed evidence-based guidance to inform plasma transfusion decisions in common clinical scenarios. Data from additional randomized studies will be required to establish more comprehensive and definitive guidelines for plasma transfusion.

BACKGROUND: Benchmarking transfusion activity may help to eliminate inappropriate use of blood products. The goal of this study was to measure and to compare the current transfusion practice and to identify predictors of transfusion in public hospitals to develop strategies to optimize transfusion practices. STUDY DESIGN AND METHODS: This was a prospective observational study in 18 randomly selected public hospitals from April 2004 to February 2005. Primary outcome measures were the amount of intra- and postoperative blood components transfused and intercenter variability of transfusion rate. Secondary outcome measures were prevalence of preoperative anemia, calculated perioperative blood loss, and lowest measured perioperative hemoglobin (Hb) level. RESULTS: Adult patients undergoing primary unilateral total hip replacement (THR, n = 1401), primary unilateral knee replacement (TKR, n = 1296), hemicolectomy (HECOC, n = 148), and coronary artery bypass graft (CABG) surgery (n = 777) were enrolled. Due to the small number, data of HECOC patients were not fully analyzed. In the remaining procedures, there was a large intercenter variability in the percentage of patients who received transfusions: THR 16 to 85 percent, TKR 12 to 87 percent, and CABG 37 to 63 percent. In the patients who received transfusions, the number of red blood cells (RBC) units transfused varied significantly. There was also a considerable intercenter variability in RBC loss. The prevalence of preoperative anemia was 19 percent and identical in both sexes. The incidence of preoperative anemia was three times higher in patients who received transfusions compared to those who did not. CONCLUSION: This study demonstrates a high intercenter variability in RBC transfusions and RBC loss in standard surgical procedures. Whereas the variability in blood loss remains largely unexplained, the main predictors for allogeneic RBC transfusions are preoperative and nadir Hb and surgical RBC loss.

Preoperative anaemia is common in patients undergoing orthopaedic and other major surgery. Anaemia is associated with increased risks of postoperative mortality and morbidity, infectious complications, prolonged hospitalization, and a greater likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the clinical and economic disadvantages of RBC transfusion in treating perioperative anaemia has prompted recommendations for its restriction and a growing interest in approaches that rely on patients' own (rather than donor) blood. These approaches are collectively termed 'patient blood management' (PBM). PBM involves the use of multidisciplinary, multimodal, individualized strategies to minimize RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies on approaches (pillars) that detect and treat perioperative anaemia and reduce surgical blood loss and perioperative coagulopathy to harness and optimize physiological tolerance of anaemia. After the recent resolution 63.12 of the World Health Assembly, the implementation of PBM is encouraged in all WHO member states. This new standard of care is now established in some centres in the USA and Austria, in Western Australia, and nationally in the Netherlands. However, there is a pressing need for European healthcare providers to integrate PBM strategies into routine care for patients undergoing orthopaedic and other types of surgery in order to reduce the use of unnecessary transfusions and improve the quality of care. After reviewing current PBM practices in Europe, this article offers recommendations supporting its wider implementation, focusing on anaemia management, the first of the three pillars of PBM.

Over one million patients per year undergo some type of procedure involving cartilage reconstruction. Polymer hydrogels, such as alginate, have been shown to be effective carriers for chondrocytes in subcutaneous cartilage formation. The goal of our current study was to develop a method to create complex structures (nose bridge, chin, etc.) with good dimensional tolerance to form cartilage in specific shapes. Molds of facial implants were prepared using Silastic ERTV. Suspensions of chondrocytes in 2% alginate were gelled by mixing with CaSO(4) (0.2 g/mL) and injected into the molds. Constructs of various cell concentrations (10, 25, and 50 million/mL) were implanted in the dorsal aspect of nude mice and harvested at times up to 30 weeks. Analysis of implanted constructs indicated progressive cartilage formation with time. Proteoglycan and collagen constructs increased with time to approximately 60% that of native tissue. Equilibrium modulus likewise increased with time to 15% that of normal tissue, whereas hydraulic permeability decreased to 20 times that of native tissue. Implants seeded with greater concentrations of cells increased proteoglycan content and collagen content and equilibrium and decreased permeability. Production of shaped cartilage implants by this technique presents several advantages, including good dimensional tolerance, high sample-to-sample reproducibility, and high cell viability. This system may be useful in the large-scale production of precisely shaped cartilage implants.

BACKGROUND: Discriminating indolent from clinically significant prostate cancer (PCa) in the initial biopsy setting remains an important issue. Prospectively evaluated diagnostic assays are necessary to ensure efficacy and clinical adoption. OBJECTIVE: Performance and utility assessment of ExoDx Prostate (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical parameters for discriminating Grade Group (GG) ≥2 PCa from GG1 PCa and benign disease on initial biopsy. DESIGN, SETTING, AND PARTICIPANTS: A two-phase adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy outcomes in men, with age ≥50 yr and prostate-specific antigen (PSA) 2-10ng/ml, scheduled for initial prostate biopsy. After EPI performance assessment during phase I, a clinical implementation document (ie, CarePath) was developed for utilizing the EPI test in phase II, where the biopsy decision is uncertain. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance evaluation of the EPI test in patients enrolled in phase I and publication of a consensus CarePath for phase II. RESULTS AND LIMITATIONS: In a total of 503 patients, with median age of 64 yr, median PSA 5.4ng/ml, 14% African American, 70% Caucasian, 53% positive biopsy rate (22% GG1, 17% GG2, and 15% ≥ GG3), EPI was superior to an optimized model of standard clinical parameters with an area under the curve (AUC) 0.70 versus 0.62, respectively, comparable with previously published results (n=519 patients, EPI AUC 0.71). Validated cut-point 15.6 would avoid 26% of unnecessary prostate biopsies and 20% of total biopsies, with negative predictive value (NPV) 89% and missing 7% of ≥GG2 PCa. Alternative cut-point 20 would avoid 40% of unnecessary biopsies and 31% of total biopsies, with NPV 89% and missing 11% of ≥GG2 PCa. The clinical investigators reached consensus recommending use of the 15.6 cut-point for phase II. Outcome of the decision impact cohort in phase II will be reported separately. CONCLUSIONS: EPI is a noninvasive, easy-to-use, gene expression urine assay, which has now been successfully validated in over 1000 patients across two prospective validation trials to stratify risk of ≥GG2 from GG1 cancer and benign disease. The test improves identification of patients with higher grade disease and would reduce the total number of unnecessary biopsies. PATIENT SUMMARY: It is challenging to predict which men are likely to have high-grade prostate cancer (PCa) at initial biopsy with prostate-specific antigen 2-10ng/ml. This study further demonstrates that the ExoDx Prostate (IntelliScore) test can predict ≥GG2 PCa at initial biopsy and defer unnecessary biopsies better than existing risk calculator's and standard clinical data.

OBJECTIVE: Postoperative pulmonary complications are a major contributor to the overall risk of surgery. We convened a patient safety summit to discuss ways to enhance physician awareness of postoperative pulmonary complications, advance postoperative pulmonary complications as a substantive public health concern demanding national attention, recommend strategies to reduce the deleterious impact of postoperative pulmonary complications on clinical outcomes and healthcare costs, and establish an algorithm that will help identify patients who are at increased risk for postoperative pulmonary complications. DATA SOURCES: We conducted PubMed searches for relevant literature on postoperative pulmonary complications in addition to using the summit participants' experience in the management of patients with postoperative pulmonary complications. DATA SYNTHESIS: Postoperative pulmonary complications are common, are associated with increased morbidity and mortality, and adversely affect financial outcomes in health care. A multifaceted approach is necessary to reduce the incidence of postoperative pulmonary complications. Identifying a measurable marker of risk will facilitate the targeted implementation of risk-reduction strategies. CONCLUSIONS: The most practicable marker that identifies patients at highest risk for postoperative pulmonary complications is the need for postoperative mechanical ventilation of a cumulative duration >48 hrs.

These cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Cancer Genetic Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Key components include the intake (medical and family histories), psychosocial assessment (assessment of risk perception), cancer risk assessment (determination and communication of risk), molecular testing for hereditary cancer syndromes (regulations, informed consent, and counseling process), and follow-up considerations. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.

The concurrent use of opioids, benzodiazepines (BZDs), and/or alcohol poses a formidable challenge for clinicians who manage chronic pain. While the escalating use of opioid analgesics for the treatment of chronic pain and the concomitant rise in opioid-related abuse and misuse are widely recognized trends, the contribution of combination use of BZDs, alcohol, and/or other sedative agents to opioid-related morbidity and mortality is underappreciated, even when these agents are used appropriately. Patients with chronic pain who use opioid analgesics along with BZDs and/or alcohol are at higher risk for fatal/nonfatal overdose and have more aberrant behaviors. Few practice guidelines for BZD treatment are readily available, especially when they are combined clinically with opioid analgesics and other central nervous system-depressant agents. However, coadministration of these agents produces a defined increase in rates of adverse events, overdose, and death, warranting close monitoring and consideration when treating patients with pain. To improve patient outcomes, ongoing screening for aberrant behavior, monitoring of treatment compliance, documentation of medical necessity, and the adjustment of treatment to clinical changes are essential. In this article, we review the prevalence and pharmacologic consequences of BZDs and/or alcohol use among patients with pain on chronic opioid therapy, as well as the importance of urine drug testing, an indispensable tool for therapeutic drug monitoring, which helps to ensure the continued safety of patients. Regardless of risk or known aberrant drug-related behaviors, patients on chronic opioid therapy should periodically undergo urine drug testing to confirm adherence to the treatment plan.