Citations

Objective: The objective of the analysis was to review the effectiveness of a care process model (CPM) developed to guide management of patients on insulin pump therapy undergoing elective surgical procedures. Methods: Electronic medical records were reviewed to assess the impact of the CPM on documentation of insulin pump status, glucose monitoring, and safety during the perioperative phase of care. Post-CPM care was compared with management provided before CPM implementation. Results: We reviewed 45 cases on insulin pump therapy in the pre-CPM cohort and 106 in the post-CPM cohort. Demographic characteristics, categories of surgery, and perioperative times were not significantly different between the 2 groups. Recommended hemoglobin A1c monitoring occurred in 73% of cases in the pre-CPM cohort but improved to 94% in the post-CPM group ( P < .01). There was a higher frequency of documentation of the insulin pump during the preoperative, intraoperative, and postanesthesia care unit segments of care in the post- vs pre-CPM periods (all P < .01). The number of cases with intraoperative glucose monitoring increased (57% pre-CPM vs 81% post-CPM; P < .01). Glycemic control was comparable between the 2 CPM periods. Hypoglycemia was rare, with only 3 episodes in the pre-CPM group and 4 in the post-CPM. No adverse events associated with perioperative insulin pump use were observed. Conclusions: This analysis adds to previous data on use of insulin pump therapy during the perioperative period. Some processes require additional attention, but data continue to indicate that a standardized approach to care can lead to a successful and safe transition of insulin pump therapy throughout the perioperative period.

Interferon (IFN)‐free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child‐Pugh‐Turcott [CPT]‐B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12‐58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69‐85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 ( P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. Conclusions: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short‐term impact on MELD score. Long‐term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population. (H epatology 2015;62:1004‐1012)

AbstractThe mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been increasingly used as immunosuppressants for recipients of solid organ transplants. Over the years, potential advantages unique to this class of immunosuppressants have been recognized, including chemoprevention by virtue of their antiproliferative effects. Prevention of malignancy after transplant through mTOR inhibitor‐based immunosuppression may have a specific practical application in transplant recipients with preexisting malignancy including hepatocellular carcinoma or cholangiocarcinoma. This review will reveal how the biochemistry of the mTOR pathway, as it pertains to chemoprevention, can support a clinical role for mTOR inhibitors in the prevention of malignancies, recurrent or de novo, after solid organ transplantation in selected patients.

AbstractBackgroundThe utility of measuring histamine and prostaglandin metabolites in the urine of patients with mastocytosis has not been critically examined in a large series of patients. This study examined the relationship between the extent of increase in urinary excretion of 11β‐prostaglandinF2α and N‐methyl histamine, with serum tryptase, whole blood serotonin, and bone marrow findings including morphology, percentage involvement, and abnormal mast cell phenotype.MethodsThis was a retrospective analysis of 90 patients who were continuously enrolled in the study for a period of 6 years (2008–2014). We recorded serum tryptase, whole blood serotonin, levels of urinary mast cell metabolites 11β‐prostaglandinF2α and N‐methyl histamine (NMH), and bone marrow findings.ResultsUrinary mast cell metabolites 11β‐prostaglandinF2α and N‐methyl histamine correlated with levels of serum tryptase, mast cell burden in the bone marrow, the presence of mast cell aggregates, and atypical mast cells on bone marrow biopsy. Whole blood serotonin did not have a significant correlation with the serum tryptase or mast cell burden in the bone marrow. Urinary NMH was significantly different between c‐kit D816V‐positive and c‐kit D816V‐negative patients, while 11β‐prostaglandinF2α was not. Urinary 11β‐prostaglandinF2α 24‐h excretion >3500 ng and NMH levels >400 μg/gm Cr corresponded with the high degree of bone marrow biopsies positive for atypical mast cells, the presence of aggregates, and c‐kit mutation.ConclusionsEasily obtained and quantified urinary metabolites of histamine (greater than twice the upper limit of normal) and prostaglandin D2 (>3.4 times the upper limit of normal) correlate well with bone marrow findings of mastocytosis.

The World Health Organization classification of non‐Hodgkin lymphoma (NHL) was introduced in 2001. However, its incorporation into clinical practice is not well‐described. We studied the distribution of NHL subtypes in adults diagnosed from 1998 to 2011, evaluated time trends, geo‐demographic correlates, and changes in 5‐year overall survival (OS). We obtained data prospectively collected by the National Cancer Data Base, which covers 70% of US cancer cases. There were 596,476 patients diagnosed with NHL. The major subtypes were diffuse large B‐cell (32.5%), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 18.6%), follicular (17.1%), marginal zone (8.3%), mantle cell (4.1%), peripheral T‐cell not‐otherwise‐specified (1.7%), Burkitt (1.6%), hairy cell (1.1%), lymphoplasmacytic (1.1%), and NHL not‐otherwise‐specified (10.8%). Over the study period, the proportion of NHL not‐otherwise‐specified declined by half, while marginal zone lymphoma doubled. The distribution of major and rare NHL subtypes varied according to demographics but less so geographically or by type of treatment facility. We noted several novel findings among Hispanics (lower proportion of CLL/SLL, but higher Burkitt lymphoma and nasal NK/T‐cell lymphoma), Asians (higher enteropathy‐associated T‐cell and angioimmunoblastic T‐cell lymphomas), Blacks (higher hepatosplenic T‐cell lymphoma), and Native Americans (similar proportions of CLL/SLL and nasal NK/T‐cell lymphoma as Asians). With the exception of peripheral T‐cell not‐otherwise‐specified and hairy cell leukemia, 5‐year OS has improved for all the major NHL subtypes. Am. J. Hematol. 90:790–795, 2015. © 2015 Wiley Periodicals, Inc.

ABSTRACT Although a large number of studies have addressed the age-related changes in bone mineral density (BMD), there is a paucity of data for the assessment of femoral strength loss with age in both genders. We determined the variation of strength with age in femurs of women and men by mechanical tests on a cohort of 100 cadaveric femurs. In addition, the age-related neck BMD loss in our cadaveric cohort was found to be similar with BMD loss of four published population-based studies. Given the strong correlation found in our cadaveric study between BMD and femoral strength, we also estimated the femoral strength of the four populations based on their reported neck BMDs. Our study showed that men's femurs in our cadaveric cohort were stronger than women's femurs by about 800 N at the same BMD level, and by 1750 N at the same age. The strength differences were not explained satisfactorily by the size difference between men's and women's bones. Similar to the findings of clinical studies, the BMD values of men at all ages were larger than that of women. The age-related loss rates in BMD and strength were not statistically different between the two genders of our cadaveric cohort. After normalization, strength decreased more than 40% faster than BMD. On average, men reached a certain BMD value about 16 years later than women, and for strength about 23 years later, which may explain the higher rate of hip fracture in postmenopausal women. In patient population cohorts men reached a similar BMD value about 16 to 25 years later than women, whereas for estimated strength, sometimes more than 40 years later. © 2015 American Society for Bone and Mineral Research.

OBJECT The primary goals of this study were: 1) to examine the influence of disease and treatment on headache in patients with sporadic vestibular schwannoma (VS); and 2) to identify clinical predictors of long-term headache disability. METHODS This was a cross-sectional observational study with international multicenter enrollment. Patients included those with primary sporadic < 3-cm VS and a separate group of general population control subjects without tumors. Interventions included a postal survey incorporating the Headache Disability Inventory (HDI), the Hospital Anxiety and Depression Scale, and a VS symptom questionnaire. The main outcome measures were univariate and multivariable associations with HDI total score. RESULTS The overall survey response rate was 79%. Data from 538 patients with VS were analyzed. The mean age at time of survey was 64 years, 56% of patients were female, and the average duration between treatment and survey was 7.7 years. Twenty-seven percent of patients received microsurgery, 46% stereotactic radiosurgery, and 28% observation. Patients with VS who were managed with observation were more than twice as likely to have severe headache disability compared with 103 control subjects without VS. When accounting for baseline differences, there was no statistically significant difference in HDI outcome between treatment modalities at time of survey. Similarly, among the microsurgery cohort, the long-term risk of severe headache disability was not different between surgical approaches. Multivariable regression demonstrated that younger age, greater anxiety and depression, and a preexisting diagnosis of headache were the primary predictors of severe long-term headache disability, while tumor size and treatment modality had little influence. CONCLUSIONS At a mean of almost 8 years following treatment, approximately half of patients with VS experience headaches of varying frequency and severity. Patient-driven factors including age, sex, mental health, and preexisting headache syndrome are the strongest predictors of long-term severe headache disability. Tumor size and treatment modality have less impact. These data may assist with patient counseling regarding long-term expectations following diagnosis and treatment.

The discovery of AQP4‐IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin‐4), as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease (IDD), has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SDs) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle. NMOSD typical brain lesions are located in areas that highly express the target antigen, AQP4, including the circumventricular organs (accounting for intractable nausea and vomiting) and the diencephalon (accounting for sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Magnetic resonance imaging brain abnormalities fulfill Barkoff criteria for multiple sclerosis in up to 10% of patients. As the spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4‐IgG targeting extracellular epitopes of AQP4 cannot be overemphasized. The rapid evolution of our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of NMOSD diagnostic criteria. Here, we describe scientific advances that have occurred since the discovery of NMO‐IgG in 2004 and review novel targeted immunotherapies. We also suggest that NMOSDs should now be considered under the umbrella term autoimmune aquaporin‐4 channelopathy .

Circulating tumor cells (CTCs) in blood are associated with poor survival of patients with breast, prostate, or colon cancer. We hypothesized that CTCs are associated with poor survival of patients with cholangiocarcinoma (CCA). Eighty‐eight patients with CCA were prospectively enrolled at Mayo Clinic Rochester between June 2010 and September 2014. The CellSearch system by Veridex was used for detection of CTCs in peripheral blood. Associations between CTC, patient and tumor characteristics, and survival were examined using the Cox's proportional hazards model. Fifteen patients (17%) were positive for CTC ≥2 and 8 patients (9%) for CTC ≥5. CTCs were associated with tumor extent. CTC ≥2 (hazard ratio [HR]: 2.5; 95% confidence interval [CI]: 1.1‐5.4; P = 0.02) and CTC ≥5 (HR, 4.1; 95% CI: 1.4‐10.8; P = 0.01) were both independent predictors of survival. In subgroup analyses, CTC ≥2 (HR, 8.2; 95% CI: 1.8‐57.5; P < 0.01) and CTC ≥5 (HR, 7.7; 95% CI: 1.4‐42.9; P = 0.02) were both associated with shorter survival among patients with metastasis. There was a trend toward association of CTC ≥5 with shorter survival in patients with nonmetastatic CCA (HR, 4.3; 95% CI: 1.0‐13.8; P = 0.06). CTC ≥2 (HR, 10.5; 95% CI: 2.2‐40.1; P < 0.01) and CTC ≥5 (HR, 10.2; 95% CI: 1.5‐42.3; P = 0.02) were both associated with shorter survival among patients with perihilar/distal CCA. CTC ≥5 was associated with shorter survival of patients with intrahepatic CCA (HR, 4.2; 95% CI: 1.1‐14.1; P = 0.04). Conclusion: CTCs were associated with more‐aggressive tumor characteristics and independently associated with survival in patients with CCA. Assessment of CTCs may be useful for identifying CCA patients at risk of early mortality. (Hepatology 2016;63:148–158)