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Objective: To identify the level of current intensivist's knowledge regarding risk assessment and intensive care unit (ICU) clinical practice pertaining to stress-related mucosal bleeding, including pharmacologic approaches for stress ulcer prevention.Design: A nationwide survey of critical care physicians.Study Population: Two thousand random physician members of the Society of Critical Care Medicine.Measurements and Main Results: The response rate was 519 (26%) of 2000, with data analysis from 501 (25.1%) usable surveys. Respondents were affiliated with internal medicine (44.3%), surgery (42.3%), and anesthesiology (12.6%). Gut ischemia was indicated as the perceived major cause of stress ulceration (59.7%). The estimated incidence of clinically important bleeding was 2% or less by 62% of respondents; however, 28.6% of physicians surveyed initiate stress ulcer prophylaxis in all ICU patients, regardless of bleeding risk. Respiratory failure was most frequently indicated as a reason for stress ulcer prophylaxis (68.6%), followed by shock/hypotension (49.4%), sepsis (39.4%), and head injury/major neurologic insult (35.2%). The first-line agents selected for stress ulcer prophylaxis include histamine-2 receptor antagonists (63.9%), followed by proton pump inhibitors (23.1%), and sucralfate (12.2%). Concern for nosocomial pneumonia was regarded as more prevalent with antisecretory therapies in those who chose sucralfate (61%) as initial therapy compared with overall respondents (26.9%) (p < .001).Conclusions: The majority of intensivists surveyed recognize stress-related mucosal bleeding as a relatively infrequent event; however, implementation of a stress ulcer prophylaxis risk stratification scheme for ICU patients is necessary. Histamine-2 receptor antagonists are consistently perceived as appropriate initial agents, although proton pump inhibitors have become first-line therapy in an increasing percentage of critical care patients, despite limited data regarding their use in this population. [ABSTRACT FROM AUTHOR]

Bone marrow lesions (BMLs) have a strong correlation to patient-reported pain, functional limitations, joint deterioration, and rapid progression to total knee arthroplasty. The Subchondroplasty (SCP) procedure uses AccuFill, a calcium phosphate bone substitute material (BSM), to treat bone defects such as microtrabecular fractures and BML. This observational, prospective, multicenter, cohort study evaluated the effect of the SCP procedure at the 2-year follow-up for 70 patients with knee BML. Under arthroscopic and fluoroscopic guidance, the BML was injected with AccuFill. Patient-reported outcomes, including Visual Analog Scale (VAS) pain, Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and modified Knee Society Score (mKSS) were collected through 24 months postoperatively. Radiographs and magnetic resonance imaging (MRI) were performed at baseline and up to 24 months postoperatively. Patient selection was not limited based on the degree of osteoarthritis (OA) as determined radiologically by the Kellgren-Lawrence (K-L) grade. For a subset of patients, patient-reported outcomes were collected up to 5 years including pain evaluation, patient knee global assessment, and satisfaction with the procedure. Preoperative radiographs indicated moderate to severe OA (K-L grades 2-4) in 65 patients (92.8%). Significant improvements ( p  < 0.0001) in mean VAS pain, IKDC, mKSS, and KOOS scores were observed compared with baseline. Kaplan-Meier survivorship free from conversion to knee arthroplasty was 76.2% at 2 years. The subset of patients followed for 5 years demonstrated low pain scores and high procedure satisfaction. This study presents statistically significant and clinically meaningful evidence of improvement in clinical outcomes following SCP for BMLs of the knee after 2 years. The survivorship rate from arthroplasty at 2 years was 76.2%. SCP for BMLs can relieve pain with a minimally invasive procedure and may delay the need for knee arthroplasty. REGISTRATION:  NCT01621893 (ClinicalTrials.gov). LEVEL OF EVIDENCE:  Level II, Prospective Cohort Therapeutic Study., Competing Interests: S.B.C. was a consultant for Zimmer Biomet during the conduct of the study. He receives royalties from Slack Inc and receives research support from Major League baseball. C.H. is currently a consultant for Corin, MaxxOrtho, and Medacta. G.L.L. has no disclosures. S.A. is a paid consultant for Arthrex, Inc. P.J.D. has nothing to disclose. D.J.W. was a consultant for Zimmer Biomet during the conduct of the study. T.Y. is a paid consultant for Arthrex. L.M.J. is on the editorial board for Bulletin for the Hospital for Joint Diseases, editorial board for JBJS Reviews, has stock or stock options in Lazurite, received research support from Mitek, Arthrex, Inc., and Smith and Nephew, and receives royalties, financial or material support by Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing. R.J.D. is an independent contractor for a surgeon consulting group “Chicagoland Joint Replacement Specialists LLC. J.F.'s disclosures are for Elute: Data Safety Monitoring Committee; Lumiheal: Medical advisory board; Medipost Consultant; Med Market Consulting; Moximed: Design surgeon for product and clinical study of the “knee unloader”: MISHA knee system; Organogenesis: Consultant; Vericel Consultant; and ZKR Orthopedics Consultant/Medical Board. P.R. was a paid employee of Zimmer Biomet during the conduct of the study. J.E.W.M. is a paid employee of Zimmer Biomet., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The advent of novel targeted therapies, including B-cell receptor (BCR) pathway and B-cell lymphoma 2 (BCL2) inhibitors, has substantially changed the treatment paradigm for chronic lymphocytic leukemia (CLL). Although targeted therapies have improved outcomes compared to traditional chemoimmunotherapy in the front-line and relapsed or refractory settings, they are associated with resistance mutations and suboptimal outcomes in certain high-risk patients. Additionally, targeted therapies are associated with drug interactions and unique adverse effect profiles which can be challenging for patients and clinicians to manage. Ongoing studies continue to address questions regarding optimal sequencing of therapies, the role of treatment combinations, and the efficacy of next-generation novel agents. This review provides a comprehensive overview regarding the clinical management of targeted therapies for CLL and applies current literature to clinical practice.

Pegaspargase is a modified version of asparaginase with prolonged asparagine depletion. It appears to be safe in adults <40 years old, but has a unique spectrum of toxicities, the risks of which appear to increase with age. The primary objective of this study was to evaluate pegaspargase tolerability and toxicity as assessed by evaluation of incidence and severity of adverse events. Secondary objectives included characterization of the reasons underlying pegaspargase discontinuation, when applicable. Grade 3/4 asparaginase-related toxicities with ≥10% incidence included: hyperbilirubinemia, hyperglycemia, hypertriglyceridemia, hypoalbuminemia, hypofibrinogenemia, and transaminitis. 63% of patients (38 of 60) received all intended doses of pegaspargase, with the most common reasons for discontinuation noted as hypersensitivity (12%), hyperbilirubinemia/transaminitis (8%), and hematopoietic transplantation in complete remission (10%). This study suggests that while hepatotoxicity and other known adverse effects are common, with careful monitoring, pegaspargase can safely be administered to adults with ALL age ≥40 years old.

Background: Various studies have demonstrated that interleukin-6 (IL-6) activates the central magnocellular arginine vasopressin (AVP)-secreting neurons in the brain to produce non-osmotic, non-volume-mediated increases in AVP. The most common toxicity of CD19+ chimeric antigen receptor (CAR) T-cells is cytokine release syndrome, which is related to increased levels of IL-6. This study will evaluate the correlation of IL-6 levels with hyponatremia in patients receiving CD19+ CAR T-cells., Materials and Methods: This is a single-center retrospective analysis of adult patients who received CD19+ CAR T-cells for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL)., Results: Hyponatremia, defined as a serum sodium (Na) ≤ 135 mEq/L, occurred in 31 (61%) patients. A change in Na > 7 mEq occurred in 32 (63%) patients, and the median lowest Na was 133 mEq/L (interquartile range (IQR): 131 - 136)). There was an inverse linear relationship between IL-6 levels and lowest Na (p = 0.001). Overall, per 10-fold increase in IL-6, Na decreased by an average of 2.68 mEq/L., Conclusion: Hyponatremia is common in patients who received CD19+ CAR T-cells. There is an inverse linear relationship between IL-6 levels and nadir Na (p = 0.001). Further studies will be needed to confirm a causative relationship between IL-6 levels and hyponatremia following CD19+ CAR T-cell infusion.

Objective: To review the literature for the treatment of classical and variant hairy cell leukemia (HCL, HCLv), evaluating efficacy, safety, and supportive care involved in the use of purine analogues (PAs), interferon, BRAF inhibitors, monoclonal antibodies, Bruton's tyrosine kinase inhibitors, and new immunotoxin, moxetumomab pasudotox-tdfk (MPT). An electronic literature search of PubMed (January 1958 to January 2019) was conducted in PubMed using the MESH terms hairy cell leukemia, hairy cell leukemia variant, cladribine, pentostatin, rituximab, interferon, vemurafenib, moxetumomab pasudotox . Study Selection and Data Extraction: Studies written in the English language were considered for this article. The significance of each article was determined by authors independently. Data Synthesis: HCL and HCLv are rare B-cell lymphoproliferative disorders, each with distinct biologies. Symptoms are characterized by pancytopenia and splenomegaly. Initial treatments for HCL were suboptimal, leading to minimal and transient remissions. PAs significantly improved outcomes, inducing remission in most patients. However, those with purine-resistant disease were left with a dearth of options, leading to implementation of vemurafenib for BRAF V600 mutated disease and chemoimmunotherapy with rituximab. Despite these advances, some HCL and a majority of HCLv patients experience relapse. Newer targeted agents offer promise for relapsed and refractory patients, including the recently approved MPT. Relevance to Patient Care and Clinical Practice: This review provides a comprehensive update on the pharmacological management of HCL and HCLv for clinicians who encounter patients with this rare disease. Conclusion: HCL and HCLv are uncommon lymphoid neoplasms that lead to a characteristic constellation of symptoms. The emergence of PAs and novel targeted agents have improved the likelihood and durability of responses for these patients.

Background: The objective of this study was to evaluate the short-term and long-term outcomes of adult patients with hematologic malignancies who received chemotherapy in the intensive care unit (ICU)., Methods: This was a retrospective, single-center study comparing the outcomes of patients with hematologic malignancies who received chemotherapy in the ICU with a matched cohort of ICU patients who did not receive chemotherapy. Conditional logistic regression and shared-frailty Cox regression were used to assess short-term (ICU and hospital) mortality and death by 12 months after hospital discharge, respectively., Results: One hundred eighty-one patients with hematologic malignancies received chemotherapy in the ICU. The ICU and hospital mortality rates were 25% and 42% for chemotherapy patients and 22% and 33% for non-chemotherapy patients, respectively. Higher severity of illness scores on ICU admission were significantly associated with higher ICU mortality (odds ratio, 1.07; P < .001) and hospital mortality (odds ratio, 1.05; P ≤ .001). Six-month and 12-month survival estimates posthospital discharge were 58% and 50%, respectively. Compared with the matched cohort of patients who did not receive chemotherapy, those who did receive chemotherapy had a significantly longer length of stay in the ICU (median, 6 vs 3 days; P < .001) and in the hospital (median, 22 vs 14 days; P = .024). In multivariable analysis, the patients who received chemotherapy in the ICU had a trend toward a higher risk of dying by 12 months (hazard ratio, 1.45; P = .08)., Conclusions: Short-term mortality was similar among patients with hematologic malignancies who did and did not receive chemotherapy in the ICU, although patients who received chemotherapy had increased resource utilization. These results may inform ICU triage and goals-of-care discussions with patients and their families regarding outcomes after receiving chemotherapy in the ICU. Cancer 2018;124:3025-36. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Objective: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL)., Data Sources: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR)., Study Selection/data Extraction: Studies of pharmacology, clinical efficacy, and safety of rituximab, ofatumumab, obinutuzumab, inotuzumab, blinatumomab, and CAR T-cells in the treatment of adult patients with ALL were identified., Data Synthesis: Conventional chemotherapy has been the mainstay in the treatment of ALL, producing cure rates of approximately 90% in pediatrics, but it remains suboptimal in adult patients. As such, more effective consolidative modalities and novel therapies for relapsed/refractory disease are needed for adult patients with ALL. In recent years, anti-CD20 antibodies, blinatumomab, inotuzumab, and CD19-targeted CAR T-cells have drastically changed the treatment landscape of B-cell ALL., Conclusion: Outcomes of patients with relapsed disease are improving thanks to new therapies such as blinatumomab, inotuzumab, and CAR T-cells. Although the efficacy of these therapies is impressive, they are not without toxicity, both physical and financial. The optimal sequencing of these therapies still remains a question.

Asparaginase administration has become a crucial component of front-line pediatric and pediatric-insipired multi-agent regimens for the treatment of acute lymphoblastic leukemia (ALL). The aim of this retrospective study was to assess the safety and feasibility of switching to Erwinia asparaginase after pegaspargase intolerance in adult ALL patients treated at Memorial Sloan Kettering Cancer Center. Our analysis included 10 patients, with a median age of 39 years (range 20-72), male predominance (90%), and a typical B-cell to T-cell ratio (70:30%) for ALL. Nine patients were switched to Erwinia asparaginase after pegaspargase hypersensitivity and one patient after grade 4 hyperbilirubinemia secondary to pegaspargase. With Erwinia asparaginase, no hypersensitivity reactions occurred and no patient developed other known clinical asparaginase-related toxicities. Laboratory adverse effects consisted of mostly mild elevation in liver enzymes. No morphologic relapses have occurred in any patient switched to Erwinia asparaginase in first remission at a follow up of 0.4-34.6 months. These findings are unique in that all of our patients received Erwinia asparaginase after hypersensitivity or intolerance to pegaspargase and 50% of them were older than 40 years of age, a population with very limited Erwinia asparaginase data. Our observations provide preliminary information that treatment with Erwinia asparaginase can proceed as scheduled in adult patients, despite pegaspargase hypersensitivity and possibly liver intolerance., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The purpose of this multi-surgeon study was to assess and compare the accuracy of acetabular component placement, leg length discrepancy (LLD), and global offset difference (GOD) between six different surgical techniques and modes of guidance in total hip arthroplasty (THA). A total of 1980 THAs met inclusion criteria. Robotic- and navigation-guided techniques were more consistent than other techniques in placing the acetabular cup into Lewinnek's safe zone (P<0.005 and P<0.05, respectively). Robotic-guided surgery was more consistent than other techniques in placing the acetabular component within Callanan's safe zone (P<0.005). No statistically significant differences were found between groups in the frequency of patients with excessive LLD. Clinically significant differences between groups were not found in the frequency of patients with excessive GOD. Level of Evidence: IV., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To review the clinical pharmacology, efficacy, and safety of blinatumomab for the treatment of pediatric and adult precursor B-cell acute lymphoblastic leukemia (B-ALL)., Data Sources: A literature search of EMBASE (1947 to April 2015), Medline (1946 to April 2015), PubMed (1996 to April 2015), the U.S. National Institutes of Health Clinicaltrials.gov, the Food and Drug Administration, and relevant meeting abstracts was conducted using the terms blinatumomab, BiTE, bispecific T-cell engager, MT103, MEDI-538, and Blincyto., Study Selection/data Extraction: Human and animal studies describing the pharmacology, pharmacokinetics and pharmacodynamics, efficacy, and safety of blinatumomab for precursor B-ALL were identified., Data Synthesis: Blinatumomab is a first-in-class bispecific T-cell engager (BiTE) antibody derived from a B-lineage specific antitumor mouse monoclonal antibody that binds to both CD19 of B-cells and CD3 of T-cells. A pivotal phase II trial demonstrated that response rates were high in a refractory or relapsed patient population, with 43% achieving complete remission (CR). Median relapse-free survival was 5.9 months for those with CR or CR with incomplete hematological recovery. Median overall survival was 6.1 months, and 60% of patients achieved minimal residual disease (MRD) negativity. The most common adverse events included pyrexia, neurological events, headache, febrile neutropenia, peripheral edema, nausea, hypokalemia, constipation, and anemia., Conclusions: Blinatumomab is a novel BiTE therapeutic monoclonal antibody that has shown promising results in patients with relapsed or refractory ALL or those achieving a CR with persistent MRD. Phase III clinical trials should define the optimal place in therapy of blinatumomab., (© The Author(s) 2015.)

The two main treatment options for total hip arthroplasty (THA), medical management and surgical intervention, have advantages and disadvantages, creating a challenging decision. Treatment decisions are further complicated in a younger population (≤50) as the potential need for revision surgery is probable. We examined the relationship of selected variables to the decision-making process for younger patients with symptomatic OA. Thirty-five participants chose surgical intervention and 36 selected medical management for their current treatment. Pain, activity restrictions, and total WOMAC scores were statistically significant (P < .05) for patients selecting surgical intervention. No difference in quality of life was shown between groups. Pain was the only predictor variable identified, however, activity restrictions were also influential variables as these were highly correlated with pain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The use of a primary prosthetic replacement such as an Austin-Moore hemi-arthroplasty in patients sustaining fractures of the femoral neck has been associated with increased post-operative medical morbidity and mortality. A retrospective review was performed using the medical records of patients greater than 59 years of age who sustained femoral neck fractures and were treated with either internal fixation or primary hemi-arthroplastic replacement at Loyola University Medical Center between 1969 and 1979. Peri-operative data were reviewed and evaluated using computer-aided statistical analysis. Comparing the two forms of surgical treatment, statistically significant factors associated with primary hemi-arthroplastic replacement included: pre-injury nursing home residence, pre-injury ambulation requiring assistance, age greater than 79 years, slight elevation in serum creatinine values, abnormal electrocardiograms in patients over 77 years of age, time from injury to surgery of four or more days, and the use of spinal anesthesia (P less than 0.05). Factors associated with internal fixation were: patient age of 79 years or less, independent ambulation, non-nursing home residence, normal lab values, normal EKGs, less than four days from injury to surgery, and the use of general anesthesia. Within the limits imposed by a retrospective review in this specific patient population, there appears to be a tendency for older, less healthy patients to have been treated with primary hemi-arthroplasty. Possibly the previously reported increased post-operative medical morbidity and mortality associated with this procedure, as compared with internal fixation, may be a result of biased patient selection, and not a fault of the procedure.

Peripheral defects in the proximal tibia can be difficult to treat during total knee arthroplasty. Attempts can be made to solve the problem with cement, cement with screws, bone grafts, metal wedges, and custom components. In vitro testing has shown that a custom-augmented prosthesis with a built-up metal wedge is mechanically superior in resisting deflections when loaded. Using modular metal wedges, the tibial tray can be customized at the time of surgery. In vitro testing has also shown the wedge to be superior to the use of cement alone or cement reinforced by screws. The authors report on modular metal wedges to augment tibial bone stock deficiency. Twenty-two knees (20 patients) were followed for a minimum of two years with an average follow-up time of 37 months. The average age of the patients at the time of surgery was 70 years. There have been no failures of this technique and no loosening of tibial components. The incidence of nonprogressive radiolucent lines was 27%. All but one patient was pain-free, and this patient's discomfort was not related to the tibial component fixation. No patient has had subsequent revision surgery. This technique should be considered in the treatment of severe peripheral tibial deficiencies in the elderly, low-demand patient.

Polycarbonate Nuclepore filters are better than cellulose filters for the direct counting of bacteria because they have uniform pore size and a flat surface that retains all of the bacteria on top of the filter. Although cellulose filters also retain all of the bacteria, many are trapped inside the filter where they cannot be counted. Before use, the Nuclepore filters must be dyed with irgalan black to eliminate autofluorescence. Direct counts of bacteria in lake and ocean waters are twice as high with Nuclepore filters as with cellulose filters.

Metastatic lesions to the bones of the foot occurred in three elderly patients. Biopsy established the diagnosis in a 90-year-old woman. In a 72-year-old man and a 79-year-old man, the diagnosis was possible from roentgenographic features. In the latter, biopsy of an additional osseous metastatic site established the diagnosis. A thorough review of the literature has yielded 72 previously reported cases of metastasis to the foot. Only 38 of these cases were histologically confirmed. Primary tumors of the colon, kidney, and lung are the most common sources of metastasis to the bones of the foot. Metastatic disease should be considered in elderly patients presenting with foot pain and osteolytic lesions, especially when there is a history of a previously diagnosed malignancy. The generally poor prognosis indicates that treatment should be clearly designed to relieve pain.