Secular trends of Blood stream infections in allogeneic hematopoietic cell transplant recipients 72 hours prior to death.

INTRODUCTION: Blood stream infections (BSI) frequently cause morbidity and mortality in allogeneic (allo) hematopoietic cell transplant (HCT) recipients. Characteristics of causative organisms shortly before death have not been previously described. Early treatment with antimicrobial agents targeting the recent surge in multidrug-resistant (MDR) pathogens may lead to better outcomes. METHODS: This is retrospective study including 529 allo HCT recipients who died between 2000 and 2013. All patients who had BSI that happened 72 hours before death were included. BSI and criteria for antimicrobial resistance were defined according to the Centers for Disease Control and Prevention and the National Healthcare Safety Network surveillance criteria. RESULTS: Overall, 104 BSI were identified from 91 patients. Bacterial infections accounted for 87% of the infections which were comprised by 37% gram-negative organisms and 50% gram-positive bacteria. The most common species were Enterococcus (30%), Staphylococcus (16%), and Pseudomonas (16%). Most enterococci were vancomycin resistant (87%), 100% of staphylococci were resistant to methicillin, and 64% of Pseudomonas were MDR. Over time there was a significant increase in vancomycin-resistant enterococcal (P = .01) and gram-negative BSI (P = .01). Blood stream infections were either the primary or secondary cause of death in 53% of patients. CONCLUSIONS: In allo HCT recipients, vancomycin-resistant enterococcal infections caused the majority of BSI 72 hours prior to death. Our findings provide information that may guide empiric antibiotic coverage in critically ill HCT recipients.

A phase I study of lenalidomide plus chemotherapy with idarubicin and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome.

Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) have poor outcomes and hematopoietic cell transplantation (HCT) is the only curative treatment. New targeted therapies improved survival in select patients with specific mutations, however management of patients without these molecular alterations is an unmet need. We conducted a phase one study of lenalidomide in combination with cytarabine/idarubicin salvage chemotherapy in patients with R/R AML and high-risk myelodysplastic syndromes. A total of 33 patients were enrolled in the study (30 AML, 3 MDS), and treated at three dose levels with 3 + 3 design. Dose-limiting toxicity (DLT) was seen in eight patients, including four hematologic DLTs. The most commonly observed non-hematologic serious adverse events were febrile neutropenia, rash, sepsis and renal injury. Dose level -1, consisting of 25 mg/d lenalidomide D1-21, 1 g/m2 cytarabine D5-8, and 8 mg/m2 idarubicin D5-7 was determined to be the maximum tolerated dose. Note, 15/33 (45%) of patients were able to receive pre-planned 21 days of lenalidomide. Overall, 18 patients achieved complete remission (CR) (n = 14) or CR with incomplete count recovery (CRi) (n = 4) with total CR/CRi rate of 56%. The 1-year and 2-year overall survival (OS) were 24% and 10%, respectively. Among responders, 10/18 underwent allogeneic HCT and had a 1-year OS of 40%. There was no molecular pattern associated with response. These data demonstrate that the combination had clinical activity in R/R AML. This regimen should be further investigated for patients who relapsed after HCT, and as a bridge therapy to HCT. (ClinicalTrials.gov identifier: NCT01132586).

Primary Care Physician Perspectives on Caring for Adult Survivors of Hematologic Malignancies and Hematopoietic Cell Transplantation.

BACKGROUND: Primary care physicians (PCPs) may face barriers to caring for hematologic malignancy and hematopoietic cell transplantation (HCT) survivors. METHODS: A Web-based survey consisting of 40 questions and 2 case scenarios was administered to 302 PCPs at 2 large integrated health care systems. The questionnaire assessed perceived barriers to delivery of care to hematologic malignancy/HCT survivors, resources available to care for cancer survivors, practices for care coordination with hematologist-oncologists, and preferred models of care delivery. RESULTS: Overall response rate was 30% (n = 86). PCPs reported several barriers such as lack of resources to facilitate care (69%), lack of awareness of screening/prevention guidelines (55%) and psychosocial needs of survivors (65%), inadequate time (65%), and patient preference to follow up with their oncologists (66%). They expressed confidence in caring for general medical issues (84%) and general cancer screening (73%), but they preferred that oncologists manage cancer-related medical issues (42%) as well as screen for cancer recurrence (52%) and secondary cancers (55%). In multivariable analysis, PCPs who had previously cared for a large number of hematologic malignancy/HCT survivors and those with a longer time since graduation from medical school had greater confidence in managing cancer-related medical issues. CONCLUSION: PCPs report several barriers in providing care to hematologic malignancy/HCT survivors. Clinical experience with this patient population is associated with greater confidence in providing survivorship care. Several barriers identified by PCPs in providing survivorship care to hematologic malignancy/HCT survivors are potentially addressable by education and clinical decision support tools and guidelines, thereby enhancing the patients' clinical experience and care coordination with hematologist-oncologists.

Using an Adaptive, Self-Directed Web-Based Learning Module to Enhance Residents' Medical Knowledge Prior to a New Clinical Rotation.

BACKGROUND: The effect of self-directed adaptive learning on internal medicine residents' knowledge prior to a new clinical rotation is not known. METHODS: We developed an adaptive, online, self-directed spaced repetition module and determined the effect on medical knowledge acquisition. We randomized postgraduate year 1 internal medicine residents into two groups. The intervention group (n = 27) received an electronic version of the clinical rotation curriculum as portable document format (PDF) files and participated in the online module, delivered via Moodle, a free, open-source learning management system. The non-intervention group (n = 27) only received the PDF files. All residents participated in a medical knowledge test at baseline and 3 months later. RESULTS: Both groups were similar at study baseline in terms of age, trainee type, years since graduation, results at United States Medical Licensing Examination (USMLE) Step 1, 2, In-Training Examination (ITE), and pre-intervention evaluation. There was a statistically significant improvement in scores on the post-intervention medical knowledge assessment for the intervention group when compared with the non-intervention group (24.2 ± 15.4% vs. 8.6 ± 9.9%, p < 0.001). CONCLUSION: An online, self-directed, adaptive spaced repetition-learning module can offer a simple and effective method to increase the medical knowledge present at the start of residents' clinical rotations.

Correction: Altered mental status and an acid-base disturbance.

In the article "A patient with altered mental status and an acid-base disturbance" (Mani S, Rutecki GW, Cleve Clin J Med 2017; 84:27-34), 2 errors occurred in Table 2. The corrected table appears with corrections shown in red. In addition, two sentences in the text regarding the osmol gap should be revised as follows: On page 31, the last 3 lines should read as follows: "When the anion gap metabolic acidosis is multifactorial, as it was suspected to be in a case reported by Tan et al,23 the osmol gap may be elevated as a consequence of additional toxic ingestions, as it was in the reported patient." And on page 33, the last sentence should read as follows: "As reflected in the revisions to MUD PILES and in the newer GOLD MARK acronym, the osmol gap has become more valuable in differential diagnosis of metabolic acidosis with an elevated anion gap consequent to an expanding array of toxic ingestions (methanol, propylene glycol, ethylene glycol, and diethylene glycol), which may accompany pyroglutamic acid-oxoproline."

Exophthalmos: A Forgotten Clinical Sign of Cushing's Syndrome.

Exophthalmos is typically associated with Graves' ophthalmopathy. Although originally described by Harvey Cushing, exophthalmos is an underappreciated sign of Cushing's syndrome. We present a case of a 38-year-old female who presented with severe bilateral proptosis and was subsequently diagnosed with Cushings disease. We discuss the possible mechanisms causing exophthalmos in patients with either endogenous or exogenous hypercortisolemia.