Early Detection of Pump Thrombosis in Patients With Left Ventricular Assist Device.

Pump thrombosis (PT) is a serious adverse event in patients receiving left ventricular assist devices (LVAD). The study aims to determine whether pump parameters and clinical data may enable early detection of PT. This retrospective study included 88 patients who received an LVAD between 2012 and 2015 among which those with intra-PT were identified. In a propensity score-matched control group observation, time periods were matched with time before thrombosis. International normalized ratio (INR) time in therapeutic range (TTR) and lactate dehydrogenase (LDH) were analyzed for 60 days preceding PT. Furthermore, pump data (power, flow, and speed) in HeartWare ventricular assist devices (HVAD) patients were analyzed 7 days before PT using a mixed-design analysis of variance to investigate temporal changes in pump data. Pump thrombosis occurred in 15 patients (13 males, age 58 ± 10 years, 7 HeartMate II and 8 HVAD). International normalized ratio therapeutic range (2.0-3.0) and acetylsalicylic acid daily doses (100-200 mg) were similar for both groups, but patients with PT had lower TTR (36% vs. 65%; p = 0.025). No significant difference in LVAD power between groups was seen at baseline (p = 0.31), and power did not change in the control group over time (p > 0.99). Lactate dehydrogenase increased already 1 week prior PT and power from 4.4 ± 0.8 W at baseline to 4.9 ± 0.8 W (p = 0.007) 2 days before readmission and to 6.5 ± 1.8 W (p = 0.015) at readmission. Pump thrombosis is associated with a lower percentage of INR TTR and elevated LDH before the event. A better monitoring of pump parameters would enable PT detection already up to 2 days in advance.

Metastatic melanoma patients' sensitivity to ipilimumab cannot be predicted by tumor characteristics.

Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. However, not all patients respond to therapy and toxicities can be severe leaving need for reliable clinical predictive markers. METHODS: We examined primary tumor characteristics including ulceration, BRAF mutation status, and Breslow depth in patients who subsequently developed stage IV disease and were treated with ipilimumab at 3 institutions. Patients in this study were not treated on clinical trials. To investigate the relationship between patient characteristics at the time of diagnosis and survival following melanoma diagnosis we utilized Cox proportional hazards models, accounting for delayed entry into the study cohort. Cox models estimate the age and institution adjusted hazard ratios for risk of death. RESULTS: Of patients (n=385) treated with ipilimumab for stage IV melanoma, 302 met inclusion criteria. The complete response to ipilimumab was 5%, partial response was 13%, 18% had stable disease, 62% had progressive disease, and 5 unknown. The median overall survival rate was 2.03 years [95% confidence interval (CI): 0.13, 3.05]. Primary tumor Breslow depth, lymphovascular invasion, BRAF status, and ulceration did not predict sensitivity to ipilimumab. In this study patient cohort, BRAF mutation (adjusted hazard ratio: 1.43, 95% CI: 0.98, 2.07) and presence of ulceration (adjusted hazard ratio: 1.47, 95% CI: 0.95, 2.26) contributed to an increased risk of death. CONCLUSIONS: The presence of ulceration did not correlate with sensitivity to ipilimumab. Ulceration of the primary tumor and a BRAF mutation were moderately associated with worse survival in patients with metastatic melanoma treated with ipilimumab.

Myelodysplastic Syndromes in Adolescent Young Adults: One Institution's Experience.

INTRODUCTION: There has been little improvement in cancer survival of adolescent and young adult (AYA) patients, aged 18 to 39 years, possibly reflecting different disease biology. Myelodysplastic syndrome (MDS) is mainly a disease of the elderly. The characteristics, outcomes, and response to treatment are not well described in the AYA population. PATIENTS AND METHODS: This was a retrospective review of patients from the Moffitt Cancer Center MDS database. We compared baseline characteristics and outcomes of the AYA population to older patients. We identified 51 AYA and 1897 older MDS patients. More female subjects and Hispanics were noted in AYA group. RESULTS: The AYA patients had higher risk disease, more circulating myeloblasts, and more hypoplastic MDS. Autoimmune disorders were more prevalent in older patients. The median overall survival (OS) was 47 months in the AYA group versus 40 months in the older group (P = .26). The median OS was 47 versus 56 months in lower risk AYA group and older group, respectively (P = .46). In the higher risk group, median OS was 82 months in the AYA group compared to 17 months in the older group (P = .001). Thirty individuals (59%) underwent allogeneic stem-cell transplantation in the AYA group versus 241 (13%) in the older group. The median OS for transplanted patients was 55 months in the AYA group and 46 months in the older group (P = .4). In the nontransplanted patients, median survival was 31 months for the AYA group and 39 months for the older group (P = .9). The rate of acute myeloid leukemia transformation was 37% versus 28% in the AYA and older groups, respectively (P = .17). No differences in use or response to hypomethylating agents were observed. Lenalidomide therapy was seldom used in AYA, as none presented with del5q. In AYA, poor karyotype was the only variable strongly associated with worse outcome. Fifteen patients had poor risk karyotypes (29%). The median OS was 47 months, not reached, and 29 months among patients with good, intermediate, and poor risk cytogenetics, respectively (P = .035). CONCLUSION: MDS is rare and tends to be more aggressive in the AYA population. Karyotype was the most important prognostic factor. Allogeneic stem-cell transplantation offered younger patients the best outcomes.

Prevalence and Pattern of Autoimmune Conditions in Patients with Marginal Zone Lymphoma: A Single Institution Experience.

BACKGROUND: Increased risk of B-cell non-Hodgkin lymphoma (NHL) in patients with autoimmune diseases is a known fact. An association may exist between marginal zone lymphoma (MZL) and certain autoimmune conditions and vice-versa. METHODS: Herein, we present the analysis of a series of consecutive patients (n = 24) diagnosed with MZL at our institution between 2008-2014. Our series, analyzed both retrospectively and prospectively, consisted of a blend of nodal, extranodal and splenic MZL. The median age was 71.8 years; M/F ratio was 2:1. The presence of autoimmune conditions was compared to their documented prevalence in the general population and tested for statistical significance using both chi-square test (χ2) and Fisher test for small number of observations (95% confidence). A P-value < 0.05 was considered significant. FINDINGS: A total of 50% of MZL patients had documented autoimmune conditions. In addition, 3 of 24 patients presented with more than one autoimmune disease. Statistically significant differences in our MZL patients were recorded for immune thrombocytopenia [ITP] (P < 0.01), autoimmune hemolytic anemia [AIHA] (P < 0.01), Hashimoto thyroiditis (P = 0.037) and rheumatoid arthritis [RA] (P = 0.021). The difference did not reach statistical significance for systemic lupus erythematosus (SLE) and psoriasis. ITP and AIHA in our cohort were synchronous with MZL diagnosis in all patients, while all non-hematologic autoimmune conditions were metachronous and diagnosed prior to MZL. CONCLUSIONS: In the course of caring for patients with MZL, a number of associated autoimmune disorders are recognized. Knowing these entities is important not only for making a correct diagnosis, but also for being able to recognize certain clinical events occurring during the course of the disease. A catalogue of autoimmune disorders associated with this type of NHL is important as they can pose formidable clinical problems for the MZL patients and their physicians.

Functional 'composite' pheochromocytoma-ganglioneuroma presenting as a pancreatic mass.

Pheochromocytomas rarely have 'composite' forms in which they demonstrate histologic features of a typical paraganglioma in combination with those of a neural component. Extra-adrenal 'composite' pheochromocytomas are distinctly uncommon. We describe herein a unique case of a 34-year-old female patient with type 1 neurofibromatosis who presented with abdominal pain and paroxysmal hypertension. Imaging revealed a pancreatic mass with biliary and pancreatic ductal dilatation and a hormonal assay led to the diagnosis of functional pheochromocytoma. She underwent surgical resection and histopathology revealed a composite paraganglioma-ganglioneuroma. Clinical, biochemical and radiological aspects of this rare tumor and its association with neurofibromatosis and other hereditary cancer syndromes are discussed.

Multiple myeloma and its therapies: to what extent do they contribute to the increased incidence of second malignant neoplasms?

BACKGROUND: The high risk of another cancer once one has been diagnosed is well known. Furthermore, a clear association exists between the use of some cytotoxic agents and chemotherapy-induced malignancies. METHODS: This review is set to explore the relationship between multiple myeloma, its modern therapies and the development of second cancers due to various genetic, immune, and environmental (including iatrogenic) factors. Most relevant publications were identified through the PubMed database and by reviewing the drug information released by the US Federal Drug Administration. FINDINGS: Our comprehensive analysis identified several retrospective population studies, cohort group analyses and a number of case reports linking myeloma with other cancers in the world literature. A majority of these studies suggest that incidence of second solid and hematologic malignancies is significantly increased in patients with multiple myeloma and its precursor lesion, monoclonal gammopathy of unknown significance. In addition, incidence of second malignancies has been found increased in the family members of these individuals, especially in their first-degree relatives. CONCLUSIONS: Analysis of the existing literature cohorts does not discriminate between the burden of second cancers in treated myeloma patients as opposed to the patients followed with the wait-and-watch approach. Notably, the rate of second malignant neoplasms in multiple myeloma may be further increased by certain myeloma therapies. These cancers include, for the most part, hematologic malignancies such as acute leukemias and certain lymphomas. While there is no question about the role of alkylating agents and topoisomerase II inhibitors in this regard, further research is necessary to determine whether the excess of second cancers represents a direct consequence of lenalidomide use.

Autoimmune phenomena in untreated and treated marginal zone lymphoma.

INTRODUCTION: Current literature suggests an association between various autoimmune conditions and marginal zone lymphoma (MZL). However, these autoimmune conditions have not been comprehensively systematized to date. As a result, their clinical implications remain largely unknown. AREAS COVERED: The authors provide a comprehensive review of the existing literature on various autoimmune abnormalities documented in the course of MZL, as well as on autoimmune alterations induced by certain MZL therapies. EXPERT OPINION: The course of MZL is accompanied by a variety of hematologic and non-hematologic autoimmune disorders. Whereas some of them could be secondary and related to the course of the MZL, others may be primary and might even favor the development of MZL itself. In addition, authentic autoimmune conditions have been documented with the use of rituximab as a single agent and the nucleoside analogs. Therefore, we believe caution should be exerted with the use of these agents in MZL patients with evidence of autoimmune disorders, as exacerbation of autoimmune phenomena can be anticipated. While the heterogeneity of the MZL subtypes represents an inherent limitation, integration of emerging information from immunology research laboratories and clinical practice could translate into improved outcomes of this disease spectrum.

The cardiac lymphatic system.

The lymphatic system, a network of vessels carrying clear interstitial fluid called lymph, is found throughout the human body. The system maintains homeostasis, receiving proteins and excess fluid from the interstitial tissues, and returning them to the venous system. Understanding of lymphatic drainage remains important in the diagnosis, prognosis, and treatment of diseases, including the metastasis of malignant diseases. Information specific to the cardiac lymphatics is scarce. Indeed, quite often the topic is not even mentioned in many medical textbooks. The goal of our review is to compile and analyze the information currently available concerning the cardiac lymphatics, hoping further to demonstrate the clinical importance of this neglected system.

Mapping the axillary nerve within the deltoid muscle.

Reports place the frequency of axillary nerve injury at 6% for all brachial plexus injuries, emphasizing the importance of an accurate anatomic description of this nerve within the deltoid in order to reduce iatrogenic injury. The aim of the present study was to explore the anatomic variations of the axillary nerve within the deltoid muscle. Fifty human cadavers were dissected, resulting in 100 nerve specimens. The anterior and posterior branches of the axillary nerve were identified and their length measured from their point of origin (split from the axillary nerve) to their termination in the deltoid muscle. In 65% of cases, the axillary nerve split into two branches (anterior and posterior) within the quadrangular space, and in the remaining 35% split within the deltoid muscle. The posterior branch of the deltoid muscle irrespectively of origin gave off a branch to the teres minor and the superior lateral brachial cutaneous nerve in 100% of cases. The branch to the posterior part of the deltoid muscle was present in 90% of cases, and the branch to the middle part of the deltoid was present in 38% of cases. The anterior branch of the deltoid muscle provided a branch to the joint capsule, a branch to the anterior part of the deltoid muscle and the middle part of the deltoid in 100% of cases. In 18% of the cases, the anterior branch of the axillary nerve provided a branch to the posterior part of the deltoid muscle. The middle part of the deltoid muscle received dual innervation in 38% of cases and the posterior part of the deltoid muscle in 8% of the cases.

Can oral sucrose reduce the pain and distress associated with screening for retinopathy of prematurity?

OBJECTIVE: Infants undergoing eye exams to screen for retinopathy of prematurity (ROP) demonstrate physiologic and behavioral manifestations of pain and distress. Oral sucrose has analgesic properties that might reduce these effects. AIM: To determine the efficacy of oral sucrose in reducing the pain/distress of eye exams for ROP. METHODS: A total of 32 infants about to undergo ROP screening exams received either oral sucrose [S] (N=16) or sterile water [C] (N=16) in a randomized, prospective and blinded fashion. Outcome measures included HR, RR, O(2) saturation, BP, pain (premature infant pain profile) and percent of time spent crying during the eye exam. RESULTS: The groups were similar in GA (weeks) (28+/-1.6), BW (kg) (1.04+/-0.26), postnatal age (days) 50.8+/-20.3, and study weight (kg) 1.88+/-0.40). Both groups demonstrated significant increases in HR, BP, and pain score in response to the exam. Infants in both groups spent the majority of time actively crying during the exam ([S] 53+/-35% vs [C] 63+/-31%. Infants receiving [S] showed a small but significant drop in O(2) saturation. No significant differences were seen between groups in physiologic or behavioral responses to the eye exam. CONCLUSION: Oral [S] was not effective in reducing pain/distress from the ROP screening exam. Alternative strategies should be considered to achieve adequate pain relief.