Search

(1) Background: Recurrent and/or metastatic patients with head and neck squamous cell carcinoma show a poor prognosis, which has not changed significantly in 30 years. Preserving quality of life is a primary goal for this subset of patients; (2) Methods: A group of 19 physicians working in South Italy and daily involved in head and neck cancer care took an anonymous online survey aimed at revealing the level of knowledge and the application of communication techniques in daily patient care; (3) Results: Several specialists, 18 out 19 (95%), considered that patient participation in therapeutic choices is mandatory. The main obstacles to complete and reciprocate communication still consist of lack of time and staff, but also in the need for greater organization, which goes beyond the multidisciplinary strategy already used; (4) Conclusions: A greater impulse to training and updating on issues related to counseling can improve communication between the different clinicians involved in the treatment plan.

The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells’ inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy.

We investigated whether DNA fragmentation in two cytometric sperm populations (PIdimmer and PIbrighter) with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultrasound (CDUS) parameters of the male genital tract. One hundred and sixty males of infertile couples without genetic abnormalities were evaluated for clinical, scrotal, and transrectal CDUS characteristics, presence of prostatitis-like symptoms (with the National Institutes of Health-Chronic Prostatitis Symptom Index) and sperm DNA fragmentation (sDF) in PIdimmer and PIbrighter populations (using TUNEL/PI method coupled with flow cytometry). Data were adjusted for age (Model 1) along with waistline, testosterone levels, smoking habit, and sexual abstinence (Model 2). According to the statistical Model 2, PIdimmer sDF was associated with testicular abnormalities, including lower clinical and ultrasound volume (r = −0.21 and r = −0.20, respectively; P < 0.05), higher FSH levels (r = 0.34, P < 0.0001) and occurrence of testicular inhomogeneity (P < 0.05) and hypoechogenicity (P < 0.05). PIbrighter sDF was associated with prostate-related symptoms and abnormal signs, including higher NIH-CPSI total and subdomain scores, a higher prevalence of prostatitis-like symptoms and of CDUS alterations such as macro-calcifications, severe echo-texture inhomogeneity, hyperemia (all P < 0.05), and higher arterial peak systolic velocity (r = 0.25, P < 0.05). Our results suggest that DNA fragmentation in PIdimmer sperm, which is related to poor semen quality, mainly originates in the testicles, likely due to apoptosis. Conversely, DNA fragmentation in PIbrighter sperm appears to mainly originate during or after transit through the prostate, increasing with the presence of an inflammatory status of the organ. These results could lead to new perspectives for the identification of therapeutic targets to reduce sDF.

Internal concealment and transportation of illegal substances by body packing is a major business with very high profits, attracting criminals all over the world. As body packers are rarely arrested, it is difficult to quantify their proportion in the general population and, consequently, identify the countries involved in this kind of drug traffic; as a consequence, the percentage of undetected cases is undoubtedly high. The aim of this study is to provide useful information concerning the country of origin of body packers travelling to Italy through the analysis of the United Nations Office on Drugs and Crime Individual Drug Seizures Report database in the period 2010–2015. Results of our study highlighted a total of 85 cases, producing a total of 52.4 kg of drugs transported through body packing towards Italy. Data obtained from our analysis could represent an useful starting point to: (a) enhance police controls on people coming from targeted countries and improve collaborations between Italian Police Forces and those of other countries; (b) understand the reason why some cities/airports are so frequently used in drug trafficking through body packing and, as a consequence, enhance police controls in these places; and (c) train airport security staffs in international airports recognized as important departure points for body packers travelling to Italy.

Piracetam is a positive allosteric modulator of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor that has been frequently used in the treatment of cognitive disorders. Press and internet reports indicate that the use of piracetam, as a heroin adulterant, has spread rapidly in some countries, especially in Asia and Europe. Its use, as adulterant, is believed to produce more profound desirable effects, while decreasing hangover. Recent surveys demonstrated that piracetam protects neurons from heroin-induced apoptosis. The protective role of this adulterating substance may be related to restoration of beta-endorphin levels and to its neuroprotective effects. The aim of this paper is to review the relevant literature and suggest the main hypothetical mechanisms that justify its use as a heroin adulterant, try to understand if its use could help people who want to come off heroin by reducing withdrawal symptoms and, finally, give useful information that permit us to understand why drug trafficking organisations started to use piracetam as heroin adulterant.

Background: This prospective surveillance study was designed to estimate the incidence of healthcare-associated infections (HAIs) and to analyze the risk factors for their development in a pediatric neurosurgical unit. Methods: The study was performed in an Italian teaching hospital from October 2008 through March 2010. All children (0–18 years) undergoing neurosurgery were included and monitored daily for the development of HAIs. Results: The study included 260 patients, with a mean age of 4.3 ± 4.7 years. Thirty-six HAIs were detected in 25 patients; catheter-related infections were the most frequent. Etiological identification was available in 22 cases; Gram-negative bacteria were the most commonly isolated pathogens. The incidence density was 11.0/1,000 patient days, and the incidence rate was 13.8/100 patients. The crude mortality was 0%. The risk of developing HAIs was related to the length of hospital stay, while the higher the age of the patients, the lower the risk of developing HAIs. Conclusion: To our knowledge, this survey is the first study to evaluate the overall incidence of HAIs and to explore the risk factors implicated in their development in neurosurgical pediatric patients. The most effective strategies to prevent these infections are reduction of the length of the hospital stay and improvement in device management.

BackgroundSomatostatin analogs (SA) are the cornerstone in the medical treatment of acromegaly, used as either primary or adjunctive therapy. In particular, SA are effective in inducing the biochemical remission of the disease and tumor shrinkage, although only few cases of complete disappearance of the pituitary tumor in patients treated with SA as long-acting formulations have been reported. SA withdrawal has been demonstrated to keep safe levels of GH and IGF1 at least in a small subset of patients well responsive to SA, although it is generally followed by disease recurrence after several months.Case reportA 61-year-old female patient bearing a very large GH-secreting pituitary macroadenoma was treated with 12-month lanreotide Autogel (ATG), at the initial dose of 120 mg/28 days. After 3 months, GH and IGF1 levels were fully normalized, to prolong the administration interval from 28 to 56 days. After 6 months of treatment, a significant tumor shrinkage (90% of baseline size) was observed, whereas GH and IGF1 excess was still well controlled. After 12-month therapy, a complete disappearance of the pituitary tumor was observed, and the hormonal evaluation confirmed the complete biochemical remission of acromegaly. Lanreotide ATG treatment was withdrawn. The clinical, biochemical, and radiological remission of acromegaly was maintained 24 months after lanreotide ATG treatment discontinuation, without evidence of disease recurrence.ConclusionsThis report represents an exemplary case of the potentiality of treatment with lanreotide ATG in inducing a complete remission of acromegalic disease, persistent after a long period of time from treatment withdrawal.

Cushing’s syndrome is commonly complicated with an impairment of glucose metabolism, which is often clinically manifested as diabetes mellitus. The development of diabetes mellitus in Cushing’s syndrome is both a direct and indirect consequence of glucocorticoid excess. Indeed, glucocorticoid excess induces a stimulation of gluconeogenesis in the liver as well as an inhibition of insulin sensitivity both in the liver and in the skeletal muscles, which represent the most important sites responsible for glucose metabolism. In particular, glucocorticoid excess stimulates the expression of several key enzymes involved in the process of gluconeogenesis, with a consequent increase of glucose production, and induces an impairment of insulin sensitivity either directly by interfering with the insulin receptor signaling pathway or indirectly, through the stimulation of lipolysis and proteolysis and the consequent increase of fatty acids and amino acids, which contribute to the development of insulin resistance. Moreover, the peculiar distribution of adipose tissue throughout the body, with the predominance of visceral adipose tissue, significantly contributes to the worsening of insulin resistance and the development of a metabolic syndrome, which participates in the occurrence and maintenance of the impairment of glucose tolerance. Finally, glucocorticoid excess is able to impair insulin secretion as well as act at the level of the pancreatic beta cells, where it inhibits different steps of the insulin secretion process. This phenomenon is probably responsible for the passage from an impairment of glucose tolerance to an overt diabetes mellitus in susceptible patients with Cushing’s syndrome.

Summary We describe the case of a 3-year-old boy with a subtotal amputation of the right foot who received treatment for pain via a peripheral catheter positioned at the level of the sciatic nerve (lateral approach).We administered a continuous infusion of 0.2% ropivacaine, 0.4 mg·kg−1·h−1 plus clonidine 0.12 μg·kg−1·h−1 for 21 days. Pain relief was complete and the patient did not require any further rescue analgesia throughout the period even during medications and surgical treatment in our intensive care unit. We discuss the safety and efficacy of the use of a peripheral continuous infusion in children compared with other techniques of analgesia.

Background and Objectives To compare ropivacaine, levo-bupivacaine, and racemic bupivacaine for caudal blockade in children. Methods Using a prospective observer blinded design, 60 sevoflurane anesthetized children (1 to 7 years) undergoing minor subumbilical surgery, were randomized to receive a caudal block (1 mL/kg) with either ropivacaine 0.2%, racemic bupivacaine 0.25%, or levo-bupivacaine 0.25%. Postoperative analgesia (number of patients needing supplemental analgesia as defined by an objective pain score [OPS] score of ≥ 5; time to first analgesic demand) during the first 24 postoperative hours was chosen as the primary end-point. Early postoperative motor block (3-point scale) was assessed as a secondary end-point. Results All blocks were judged to be clinically successful based on the presence of adequate intraoperative and early postoperative analgesia. An OPS score ≥ 5 was found in 5/20 patients in each study group. No difference regarding the time to first analgesic demand was found between the study groups. The use of ropivacaine (P = .02), but not levo-bupivacaine (P = .18), was found to be associated with less motor block during the first postoperative hour compared with racemic bupivacaine. Conclusion All 3 investigated local anesthetics were found to be clinically comparable despite the slight reduction of early postoperative motor block associated with the use of ropivacaine.

Introduction: Hyperprolactinemia and hypogonadism are reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of testosterone replacement and cabergoline (CAB) treatment on the metabolic profile in male hyperprolactinemic patients. Patients and Methods: Thirty-two men with prolactinomas, including 22 with total testosterone (TT) 8 nmol/l (non-HG, 31%), were entered in the study. In all patients, metabolic parameters were assessed at diagnosis and after 12- and 24-month treatment. Results: Compared to non-HG patients, at baseline the HG patients had higher waist circumference (WC). TT significantly correlated with body mass index (BMI). Twelve-month CAB induced PRL normalization in 84%. HG prevalence significantly decreased (28%) and non-HG prevalence significantly increased (72%). Anthropometric and lipid parameters, fasting insulin (FI), insulin sensitivity index (ISI₀), homeostatic model assessment of insulin secretion (HOMA-β) and homeostatic model assessment of insulin resistance (HOMA-IR) significantly improved compared to baseline. TT was the best predictor for FI. Percent change (Δ) of TT significantly correlated with ΔCholesterol, ΔWeight and ΔBMI. Compared to non-HG patients, the HG patients had a higher weight, BMI, WC and HOMA-β. In HG, testosterone replacement was started. After 24 months, PRL normalized in 97%. HG prevalence significantly decreased (6%) and non-HG prevalence significantly increased (94%). Anthropometric and lipid parameters, FI, ISI₀, HOMA-β and HOMA-IR significantly improved compared to baseline, with FI, ISI₀, HOMA-β and HOMA-IR further ameliorating compared to the 12-month evaluation. Compared to non-HG patients, the HG patients still had a higher weight, BMI and WC. Conclusions: In hyperprolactinemic hypogonal men, proper testosterone replacement induces a significant improvement in the metabolic profile, even though the amelioration in the lipid profile might reflect the direct action of CAB.

Introduction: Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. Patients and Methods: 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. Results: Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022). Conclusions: CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB.

BackgroundThe GH/insulin-like growth factor 1 axis is physiologically involved in the regulation of electrolytes and water homeostasis by kidneys, and influences glomerular filtration and tubular re-absorption processes. The aim of the study was to investigate renal structure and function in acromegalic patients during active disease and disease remission.PatientsThirty acromegalic patients (15 males and 15 females), aged 32–70 years, were enrolled for the study. Tende novopatients had active disease, whereas 20 patients showed disease remission 1 year after medical treatment with somatostatin analogs (SA) (ten patients) or surgery (ten patients). Thirty healthy subjects matched for age, gender, and body surface area were enrolled as controls.ResultsIn both active (A) and controlled (C) patients, creatinine clearance (PPPPPPPPPPPPr=0.871,Pr=0.639,PConclusionsThe results of the current study demonstrated that acromegaly affects both renal structure and function. The observed changes are not completely reversible after disease remission.

Cushing’s syndrome (CS) causes metabolic abnormalities that determine an increased cardiovascular risk not only during the active phase of the disease but also for a long time after cure. Cardiovascular complications, such as premature atherosclerosis, coronary artery disease, heart failure, and stroke, in patients with CS cause a mortality rate higher than that observed in a normal population. The increased cardiovascular risk is mainly due to metabolic complications, such as metabolic syndrome, but also to vascular and cardiac alterations such as atherosclerosis and cardiac structural and functional changes. In the clinical management of patients with CS the focus should be on identifying the global cardiovascular risk and the aim should be to control not only hypertension but also other correlated risk factors, such as obesity, glucose intolerance, insulin resistance, dyslipidemia, endothelial dysfunction and the prothrombotic state. Considering that remission from hypercortisolism is often difficult to achieve and that the cardiovascular risk can persist even during disease remission, care and control of all cardiovascular risk factors should be one of the primary goals during the follow-up of these patients.