Hepatitis C cure improved patient‐reported outcomes in patients with and without liver fibrosis in a prospective study at a large urban medical center

Patient‐reported outcomes (PROs) are important measures of quality of life. Direct‐acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA‐based HCV cure on PROs and liver‐related outcomes in real‐world patients at a large urban medical center. The short form (SF)‐36 and three additional validated instruments were used. F3‐4 fibrosis was defined as > 9.6 kPa by transient elastography (TE); S2‐3 steatosis was defined as > 270 dB/m by TE‐controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n = 16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF‐36 vitality score, measured baseline to SVR12: 63 versus 82, P < .001 (n = 111). Scores in 24 of 25 PRO domains improved at SVR12 (P < .05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P < .005), but steatosis was unchanged (P = .58). Patients with baseline F0‐2 fibrosis and those with F3‐F4 fibrosis both improved in 22 domains. Patients with baseline S0‐S1 steatosis improved in more domains (23) than patients with S2‐S3 steatosis (19). At baseline, patients with F3‐F4 fibrosis and patients with S2‐3 steatosis had worse scores in certain PRO domains than patients with F0‐2 fibrosis or S0‐S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment.     

MRI texture analysis in acromegaly and its role in predicting response to somatostatin receptor ligands

Purpose

Given the paucity of reliable predictors of tumor recurrence, progression, or response to somatostatin receptor ligand (SRL) therapy in acromegaly, we attempted to determine whether preoperative MR image texture was predictive of these clinical outcomes. We also determined whether image texture could differentiate somatotroph adenomas from non-functioning pituitary adenomas (NFPAs).

Methods

We performed a retrospective study of patients with acromegaly due to a macroadenoma who underwent transsphenoidal surgery at our institution between 2007 and 2015. Clinical data were extracted from electronic medical records. MRI texture analysis was performed on preoperative non-enhanced T1-weighted images using ImageJ (NIH). Logistic and Cox models were used to determine if image texture parameters predicted outcomes.

Results

Eighty-nine patients had texture parameters measured, which were compared to that of NFPAs, while 64 of these patients had follow-up and were included in the remainder of analyses. Minimum pixel intensity, skewness, and kurtosis were significantly different in somatotroph adenomas versus NFPAs (area under the receiver operating characteristic curve, 0.7771, for kurtosis). Furthermore, those with a maximum pixel intensity above the median had an increased odds of IGF-I normalization on SRL therapy (OR 5.96, 95% CI 1.33–26.66), which persisted after adjusting for several potential predictors of response. Image texture did not predict tumor recurrence or progression.

Conclusion

Our data suggest that MRI texture analysis can distinguish NFPAs from somatotroph macroadenomas with good diagnostic accuracy and can predict normalization of IGF-I with SRL therapy.

     

Caffeine Inhibits EGF-Stimulated Trophoblast Cell Motility through the Inhibition of mTORC2 and Akt

Impaired trophoblast invasion is associated with pregnancy disorders such as early pregnancy loss and preeclampsia. There is evidence to suggest that the consumption of caffeine during pregnancy may increase the risk of pregnancy loss; however, little is known about the direct effect of caffeine on normal trophoblast biology. Our objectives were to examine the effect of caffeine on trophoblast migration and motility after stimulation with epidermal growth factor (EGF) and to investigate the intracellular signaling pathways involved in this process. Primary first-trimester extravillous trophoblasts (EVT) and the EVT-derived cell line SGHPL-4 were used to study the effect of caffeine on EGF-stimulated cellular motility using time-lapse microscopy. SGHPL-4 cells were further used to study the effect of caffeine and cAMP on EGF-stimulated invasion of fibrin gels. The influence of caffeine and cAMP on EGF-stimulated intracellular signaling pathways leading to the activation of Akt were investigated by Western blot analysis. Caffeine inhibits both EGF-stimulated primary EVT and SGHPL-4 cell motility. EGF stimulation activates phosphatidylinositol 3-kinase, and Akt and caffeine inhibit this activation. Although cAMP inhibits both motility and invasion, it does not inhibit the activation of Akt, indicating that the effects of caffeine seen in this study are independent of cAMP. Further investigation indicated a role for mammalian target of rapamycin complex 2 (mTORC2) as a target for the inhibitory effect of caffeine. In conclusion, we demonstrate that caffeine inhibits EGF-stimulated trophoblast invasion and motility in vitro and so could adversely influence trophoblast biology in vivo.     

Cognitive Effects of Chemotherapy-Induced Menopause in Breast Cancer

This study examined whether chemotherapy-induced menopause affects cognitive functioning in women with early breast cancer. The neuropsychological performance of 121 breast cancer patients (age M?=?49.62, SD?=?8.11, range?=?25.25–67.92) treated with chemotherapy was assessed pre-chemotherapy, as well as 1, 6, and 18 months post-chemotherapy completion. Linear mixed modeling was used to evaluate the data. Type of menopause (pre, chemotherapy-induced, and post menopause) was found to significantly interact with cognitive performance on two cognitive variables. Specifically, chemotherapy-induced menopausal women did not show any significant changes in performance on an abstract reasoning task, while the pre-menopausal and post-menopausal groups significantly improved over time. A significant interaction on a test of finger dexterity and coordination was also found, although inspection of the results indicated that this was due to a significant improvement in the pre-menopausal groups at 6 months post chemotherapy. After chemotherapy most cognitive variables showed improvements over time, although two indicators of verbal memory showed significant declines immediately after chemotherapy, with improvement by 18 months post completion. The current study found little evidence to suggest that chemotherapy-induced menopause broadly affects cognitive functioning after treatment administration. However, longer follow-up assessments are warranted to assess the long-term effects of combined chemotherapy and endocrine treatment.     

Cardiac Resynchronization Therapy: Do Women Benefit More Than Men?

Gender and Resynchronization Therapy. Introduction: Women are underrepresented in cardiac resynchronization therapy (CRT) trials. Whether there is a gender difference in the benefit derived from CRT has not been well studied. Methods: This study included 728 consecutive CRT recipients at our institution who met guidelines for placement of a CRT device. Clinical characteristics and echocardiographic parameters were collected at baseline and after CRT; Kaplan–Meier survival analysis was performed using a national death and location database. The effects and outcome of CRT were compared between women and men. Results: Of 728 patients, 166 were female (22.8%). Female patients were younger than male patients (66.0 ± 11.9 years vs 69.4 ± 10.9 years; P < 0.001) and more often had nonischemic cardiomyopathy (68% vs 36%; P < 0.001). Both female and male patients had significantly improved clinical and echocardiographic parameters after CRT. The magnitude of improvement was similar in women and men, except that improvement in New York Heart Association (NYHA) class was greater in women than in men (–0.79 ± 0.78 vs –0.56 ± 0.85; P = 0.009). Although women were at lower risk of death than men after CRT (hazard ratio, 0.51; 95% confidence interval, 0.35–0.75; P < 0.001, unadjusted), multivariate analysis indicated gender was not, but age at CRT placement, cardiomyopathy cause, NYHA class, and lead location were independent predictors of survival. Conclusion: Female CRT recipients seem to achieve greater survival benefit than male recipients. However, this benefit is majorly driven by nonischemic cardiomyopathy and other clinical factors. (J Cardiovasc Electrophysiol, Vol. 23, pp. 172‐178, February 2012)     

Influence of HTLV-1 on the clinical, microbiologic and immunologic presentation of tuberculosis

ABSTRACT: BACKGROUND: HTLV-1 is associated with increased susceptibility to Mycobacterium tuberculosis infection and severity of tuberculosis. Although previous studies have shown that HTLV-1 infected individuals have a low frequency of positive tuberculin skin test (TST) and decreasing in lymphoproliferative responses compared to HTLV-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of M. tuberculosis infection. Therefore the reasons why HTLV-1 infection increases susceptibility to infection and severity of tuberculosis are not understood.The aim of this study was to evaluate how HTLV-1 may influence the clinical, bacteriologic and immunologic presentation of tuberculosis. METHODS: The study prospectively enrolled and followed 13 new cases of tuberculosis associated with HTLV-1 (cases) and 25 patients with tuberculosis without HTLV-1 infection (controls). Clinical findings, bacterial load in the sputum, x-rays, immunological response and death were compared in the two groups. RESULTS: There were no differences in the demographic, clinical and TST response between the two study groups. IFN-gamma and TNF-alpha production was higher in unstimulated cultures of mononuclear cells of case than in control patients (p < 0.01). While there was no difference in IFN-gamma production in PPD stimulated cultures, TNF-alpha levels were lower in cases than in controls (p = 0.01). There was no difference in the bacterial load among the groups but sputum smear microscopy results became negative faster in cases than in controls. Death only occurred in two co-infected patients. CONCLUSION: While the increased susceptibility for tuberculosis infection in HTLV-1 infected subjects may be related to impairment in TNF-alpha production, the severity of tuberculosis in co-infected patients may be due to the enhancement of the Th1 inflammatory response, rather than in their decreased ability to control bacterial growth.