BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report

This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.     

Multiple facets in the control of acromegaly

Aims

The current article provides a brief overview of the criteria for defining disease control in acromegaly.

Methods

This was a retrospective, narrative review of previously published evidence chosen at the author’s discretion along with an illustrative case study from Latin America.

Findings and Conclusions

In the strictest sense, “cure” in acromegaly is defined as complete restoration of normal pulsatile growth hormone secretion, although this is rarely achieved. Rather than “cure”, as such, it is more appropriate to refer to disease control and remission, which is defined mainly in terms of specific biochemical targets (for growth hormone and insulin-like growth factor-1) that predict or correlate with symptoms, comorbidities and mortality. However, optimal management of acromegaly goes beyond biochemical control to include control of tumour growth (which may be independent of biochemical control) and comprehensive management of the symptoms and comorbidities typically associated with the disease, as these may not be adequately managed with acromegaly-specific therapy alone.

     

Female sexual desire disorders: subtypes,classification, personality factors and new directions for treatment

Lack of sexual interest is highly prevalent in the general female population and, for more than two decades, low sexual desire has been the most common presenting problem in clinical institutions. The renewed interest in female sexual dysfunction has recently focused on biological and classification aspects whilst personality- and partner-related factors, as well as theoretical concepts, have largely been neglected. After critically reviewing the current diagnostic systems for female desire disorders, this paper specifically addresses the issues of personality and life history factors. In two empirical studies, 50 patients with low sexual desire were compared to a group of 100 sexually functional women by employing both semi-structured clinical interviews and a set of self-developed and standardised questionnaires. The results of these studies indicate that women seeking help for desire disorders exhibit marked signs of mood instability and a low and fragile self-regulation and self-esteem. In addition, they tend to be more worried, anxious, introverted and conventional when compared to sexually functional women. Interestingly, no significant differences in the variables relating to partnership quality in general could be detected. Although caution is needed due to sample size and methodological limitations, our results suggest a substantial level of at least subclinical psychiatric symptoms like mood-disorders, low self-esteem and feelings of guilt in women with sexual desire disorders. These problems seem to be rather deep-rooted and particularly affect the self-regulation and the inner balance of the personality. Overall, female sexual dysfunctions and low desire, in particular, cannot be conceptualised as discrete phase disorders, but rather as a global inhibition of sexual response together with a history of mood disorder, specific personality factors and an elevated level of psychological stress. This combination calls for broad-band treatment approaches where individual and interpersonal aspects can be taken into account simultaneously. In addition, the ubiquitous comorbidity, both with other sexual dysfunctions and with various personality and psychological problems, and the developmental sequence of the sexual problems must be adequately considered.     

Effect of vildagliptin as add-on therapy to a low-dose metformin

AIM: To evaluate the efficacy and safety of the addition of vildagliptin to low-dose metformin and compare it to an uptitration of metformin in type 2 diabetes mellitus (T2DM) patients who have inadequate control with metformin monotherapy.METHODS: Eligible patients were randomized to receive vildagliptin 100 mg qd or metformin (500 mg qd for 2 wk and then 500 mg bid) added to open label metformin 500 mg bid for the 24 wk. The primary endpoint was baseline to endpoint hemoglobin A_1c (HbA_1c) change.RESULTS: The adjusted mean change from baseline in HbA_1c at the 24th wk was -0.51% in the vildagliptin/metformin group (mean baseline HbA_1c: 7.4%) and -0.37% in the metformin monotherapy group (mean baseline HbA_1c: 7.3%). The mean difference was -0.14% with 95% Confidence Interval (-0.24%, -0.05%). As non-inferiority (margin of 0.4%) was achieved, a test for superiority was performed. This test showed statistically significant superiority of the combination over monotherapy group (P = 0.002). Gastrointestinal (GI) adverse events were significantly more frequent in the metformin group than the combination group (21.0% vs 15.4%, P = 0.032).CONCLUSION: In patients with T2DM inadequately controlled with metformin up to 1000 mg daily, the addition of vildagliptin 100 mg daily achieved larger HbA_1c reduction with fewer GI events than with increasing the metformin dose.     

Efficacy and safety of vildagliptin/pioglitazone combination therapy in Korean patients with diabetes

AIM: To assess the efficacy and safety of vildagliptin/pioglitazone combination therapy in Korean patients with type 2 diabetes mellitus (T2DM).METHODS: This was a post hoc analysis in Korean patients, from a 24-wk, randomized, active-controlled, double-blind, parallel-group, multicenter study. Eligible patients were aged between 18 and 80 years, drug naive, and had been diagnosed with T2DM [hemoglobin A_1c (HbA_1c): 7.5%-11.0% and fasting plasma glucose (FPG): < 270 mg/dL (< 15 mmol/L)]. Patients were randomized (1:1:1:1) to receive the vildagliptin/pioglitazone combination at 100/30 mg q.d. (high-dose) or 50/15 mg q.d. (low-dose), vildagliptin 100 mg q.d., or pioglitazone 30 mg q.d. monotherapies. The primary outcome measure was change in HbA_1c from baseline to endpoint.RESULTS: The distribution of baseline demographic and clinical parameters was well balanced between treatment groups. The overall mean age, body mass index, HbA_1c, FPG, and duration of disease were 50.8 years, 24.6 kg/m², 8.6%, 10.1 mmol/L, and 2.2 years, respectively. Adjusted mean changes (± standard error) in HbA_1c from baseline (~8.7%) to week 24 endpoint were -2.03% ± 0.16% (high-dose, N = 34), -1.88% ± 0.15% (low-dose, N = 34), -1.31% ± 0.21% (vildagliptin, N = 36), and -1.52% ± 0.16% (pioglitazone, N = 36). The high-dose combination therapy demonstrated greater efficacy than monotherapies [vildagliptin (P = 0.029) and pioglitazone (P = 0.027)]. Percentage of patients achieving HbA_1c < 7% and ≤ 6.5% was the highest in the high-dose group (76% and 68%) followed by low-dose (58% and 47%), vildagliptin (59% and 37%), and pioglitazone (53% and 28%) groups. The overall incidence of adverse events was comparable.CONCLUSION: In Korean patients, first-line treatment with high-dose combination therapy improved glycemic control compared to pioglitazone and vildagliptin monotherapies, consistent with results published for the overall study population.     

Fiber type-related changes in rat skeletal muscle calcium homeostasis during aging and restoration by growth hormone

The mechanisms by which aging induces muscle impairment are not well understood yet. We studied the impact of aging on Ca2+ homeostasis in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscles of aged rats by using the fura-2 fluorescent probe. In both muscles aging increases the resting cytosolic calcium concentration ([Ca2+]i). This effect was independent on calcium influx since a reduced resting permeability of sarcolemma to divalent cations was observed in aged muscles likely due to a reduced activity of leak channels. Importantly the effects of aging on resting [Ca2+]i, fiber diameter, mechanical threshold and sarcolemmal resting conductances were less pronounced in the soleus muscle, suggesting that muscle impairment may be less dependent on [Ca2+]i in the slow-twitch muscle. The treatment of aged rats with growth hormone restored the resting [Ca2+]i toward adult values in both muscles. Thus, an increase of resting [Ca2+]i may contribute to muscle weakness associated with aging and may be considered for developing new therapeutic strategies in the elderly.