GH provocative tests stimulate the growth in children with idiopathic short stature.

CONTEXT: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS). OBJECTIVE: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature. DESIGN: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up. METHODS: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues. RESULTS: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2-1.0) cm and 2.4 (1.7-3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were -4.0 (-5.4--2.1) SDS and 0.1 (-1.9-1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219). CONCLUSIONS: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined.

Survival predictors of radioiodine-refractory differentiated thyroid cancer treated with lenvatinib in the real-life.

CONTEXT: Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The definition of predictive factors of survival is incomplete. OBJECTIVE: To identify pre- and post- treatment survival predictors in a real-life cohort of RR-DTC treated with lenvatinib. DESIGN: Multicenter, retrospective, cohort study. SETTING: Three Italian thyroid cancer referral centers. PARTECIPANTS: 55 RR-DTC treated with lenvatinib. MAIN OUTCOME MEASURES: Progression-free survival (PFS) and overall survival (OS). RESULTS: Lenvatinib was the first-line kinase-inhibitor in 96.4% of subjects. Median follow-up was 48 months. Median PFS and OS were 26 (95% CI 19.06-32.93) and 70 months (95% CI 36-111.99), respectively. Pre-treatment setting: Eastern Cooperative Oncology Group (ECOG) performance status was independently related to PFS (p < 0.001; HR 18.82; 95% CI 3.65-97.08: score 0-1 as reference) and OS (p = 0.001; HR 6.20; 95% CI 2.11-18.20; score 0-1 as reference); radioactive iodine (RAI)-avidity was independently related to PFS (p = 0.047; HR 3.74; 95% CI 1.01-13.76; avid disease as reference). Patients with good ECOG status (0-1) and RAI-avid disease obtained objective response in 100% of cases and achieved a median PFS of 45 months without any death upon a median follow-up of 81 months. Post-treatment setting: best radiological response independently predicted PFS (p = 0.001; HR 4.6; 95% CI 1.89-11.18; partial/complete response as reference) and OS (p = 0.013; HR 2.94; 95% CI 1.25-6.89; partial/complete response as reference). CONCLUSIONS: RR-DTC with good performance status and RAI-avid disease obtain the highest clinical benefit from lenvatinib. After treatment initiation, objective response was the only independent survival predictor.

Exposure to Bisphenol A increases malignancy risk of thyroid nodules in overweight/obese patients.

Bisphenol A (BPA) is a widespread thyroid disruptor, but evidence about an association with thyroid cancer is weak. Excess body weight is a risk factor for thyroid cancer and affects activity of endocrine disruptors. Aim of the study was to investigate the association between BPA exposure and thyroid cancer, verifying the effect modification related to body weight. We performed a multicentre, cross-sectional study including consecutive patients referring for nodular goiter. The quantitative determination of BPA in serum samples was performed through high performance liquid chromatography system, coupled in tandem with ultraviolet and fluorescence detection. Ninety-six patients were included: 55 benign nodules, 41 thyroid cancers, 28 normal weight, and 68 overweight/obese. BPA was detected in 79 subjects. In the overall study population and in the group with BMI<25 kg/m2 BPA exposure was not significantly correlated to thyroid cancer (p = 0.08 and 0.759, respectively). In the group with BMI≥25 kg/m2, BPA-exposed subjects showed significantly higher risk of malignancy (OR: 5.3, p = 0.028). At multivariate analysis, such association was independent of smoking, alcohol consumption, occupational exposure, and phthalates exposure (p = 0.021 and 0.016, respectively), but was lost after adjustment for the presence of metabolic syndrome (p = 0.089). In overweight/obese subjects, BPA exposure was significantly associated with higher thyroid stimulating hormone levels. Our study suggests that BPA exposure is a risk factor for thyroid cancer in overweight/obese subjects.

An IT Platform Supporting Rectal Cancer Tumor Board Activities: Implementation Process and Impact Analysis.

Colorectal cancer (RC) is the third most common cancer, with an increasing incidence in recent years. Digital health solutions supporting multidisciplinary tumor boards (MTBs) could improve positive outcomes for RC patients. This paper describes the implementation process of a digital solution within the RC-MTB and its impact analysis in the context of the Fondazione Policlinico 'A. Gemelli' in Italy. Adopting a two-phase methodological approach, the first phase qualitatively describes each phase of the implementation of the IT platform, while the second phase quantitatively describes the analysis of the impact of the IT platform. Descriptive and inferential analyses were performed for all variables, with a p-value < 0.05 being considered statistically significant. The implementation of the platform allowed more healthcare professionals to attend meetings and resulted in a decrease in patients sent to the RC-MTB for re-staging and further diagnostic investigations and an increase in patients sent to the RC-MTB for treatment strategies. The results could be attributed to the facilitated access to the platform remotely for specialists, partly compensating for the restrictions imposed by the COVID-19 pandemic, as well as to the integration of the platform into the hospital's IT system. Furthermore, the early involvement of healthcare professionals in the process of customizing the platform to the specific needs of the RC-MTB may have facilitated its use and contributed to the encouraging quantitative results.

The effects of a structured educational program on preparedness for self-employed careers in Italian undergraduate nursing students.

BACKGROUND AND AIM OF THE WORK: In the Italian and also international contexts, there is a paucity of evidence testing whether a structured educational intervention delivered from remote might be useful in increasing the levels of preparedness for self-employed careers among third-year nursing students, despite freelance nursing careers are a promising component of the current labour market. This study aimed to test the effects of a structured educational program on the preparedness for self-employed careers in Italian undergraduate nursing students. METHODS: The study was quasi-experimental and nonrandomized and employed a pre/post-intervention approach with convenience sampling. Data were collected before the structured education program was delivered (T0) and up to one day after the instruction was delivered (T1). RESULTS: In this study, 717 third-year nursing students were enrolled. The most significant difference between T0 and T1 was in the domain of knowledge about pensions and retirement issues, followed by administrative rules knowledge. There were substantial variations between T0 and T1 in the area of logistic characteristics in determining the price of a freelance nursing activity, as well as scores in the domain of care complexity in determining the price of the independent nursing occupation. CONCLUSIONS: This study proved the short-term impacts of a structured educational program on enhancing levels of preparation for self-employed professions among Italian undergraduate nursing students. This topic requires more attention as the demands of prepared healthcare workers to undertake self-employed careers necessitate a greater capacity to properly educate nursing students for self-employed occupations within their undergraduate path.

The value of surgical admissions for malignant uterine cancer. A comparative analysis of robotic, laparoscopic, and laparotomy surgery in a university hospital.

Background: Robotic surgery for malignant uterine cancer raises issue of economic sustainability for providers. The objective of this study was to assess the value of surgical admissions for malignant uterine cancer in a University Hospital through an analysis of their costs and outcomes by comparing three different surgical approaches (laparotomy, laparoscopic, and robotic surgery). Methods: Hospitalizations between 1 January 2019 and 31 October 2021 for malignant uterine cancer surgery were selected and stratified. For each surgical approach, mean values (with 95% confidence intervals, CI) were calculated for cost items. Moreover, 30-day readmission frequency was calculated for the three approaches compared to each other. ANOVA and Student's t-test and relative risk (RR) were used for statistical analysis. A break-even analysis was carried out by evaluating the volume of robotic and non-robotic surgical admissions. Results: A total of 1,336 hospitalizations were included in the study, 366 with robotic, 591 with laparoscopic, and 379 with laparotomy surgery. Robotic surgery, compared to laparoscopic and laparotomy ones, showed a statistically significant difference (p < 0.001) in the economic margin, which was largely negative (-1069.18 €; 95%CI:-1240.44--897.92 €) mainly due to devices cost, and a lower percentage of 30-day readmissions (1.4%; 95%CI: 0.2-2.6%), with a statistically significant difference only vs. laparotomy (p = 0.029). Laparoscopic compared to laparotomy surgery showed a significantly (p < 0,001) more profitable economic margin (1692.21 €; 95%CI: 1531.75 €-1852.66 €) without a significant difference for 30-day readmissions. Break-even analysis showed that, on average, for each malignant uterine cancer elective surgery performed laparoscopically, 1.58 elective robotic surgeries are sustainable for the hospital (95% CI: 1.23-2.06). Conclusion: Break-even analysis could be a useful tool to support hospital management in planning and governance of malignant uterine cancer surgery. Systematic application of this tool will allow defining over time right distribution of robotic, laparoscopic, and laparotomy surgeries' volumes to perform to ensure both quality and economic-financial balance and therefore value of uterine oncological surgery. Concerning research, this study paves the way for a multicentric study, the extension of outcomes of malignant uterine surgery to be considered and assessed, and the future inclusion of other therapeutic interventions in the analysis.

Palliative Care for Patients with Kidney Disease.

Interest in palliative care has increased in recent times, particularly in its multidisciplinary approach developed to meet the needs of patients with a life-threatening disease and their families. Although the modern concept of palliative simultaneous care postulates the adoption of these qualitative treatments early on during the life-threatening disease (and potentially just after the diagnosis), palliative care is still reserved for patients at the end of their life in most of the clinical realities, and thus is consequently mistaken for hospice care. Patients with acute or chronic kidney disease (CKD) usually experience poor quality of life and decreased survival expectancy and thus may benefit from palliative care. Palliative care requires close collaboration among multiple health care providers, patients, and their families to share the diagnosis, prognosis, realistic treatment goals, and treatment decisions. Several approaches, such as conservative management, extracorporeal, and peritoneal palliative dialysis, can be attempted to globally meet the needs of patients with kidney disease (e.g., physical, social, psychological, or spiritual needs). Particularly for frail patients, pharmacologic management or peritoneal dialysis may be more appropriate than extracorporeal treatment. Extracorporeal dialysis treatment may be disproportionate in these patients and associated with a high burden of symptoms correlated with this invasive procedure. For those patients undergoing extracorporeal dialysis, individualized goal setting and a broader concept of adequacy should be considered as the foundations of extracorporeal palliative dialysis. Interestingly, little evidence is available on palliative and end of life care for acute kidney injury (AKI) patients. In this review, the main variables influencing medical decision-making about palliative care in patients with kidney disease are described, as well as the different approaches that can fulfill the needs of patients with CKD and AKI.

Preparedness to self-employed careers: development, validity, and reliability of an inventory for nursing students.

AIMS: To develop and psychometrically validate an inventory based on two scales: awareness regarding factors for determining the prices of freelance activities and knowledge regarding freelance-related norms among nursing undergraduate students in Italy. BACKGROUND: Although self-employed nursing careers are strategic to enhance employability, no valid scales for assessing nursing students' preparedness to undertake self-employed careers are available. DESIGN: A multi-method and multi-phase design were employed. Phase one encompassed developmental tasks for generating items and phase two included a cross-sectional data collection for determining the psychometric proprieties of the developed scales and their reliability. RESULTS: The final inventory encompassed two scales showing adequate validity and reliability after testing it on 882 Italian undergraduate nursing students. The first scale, factors for determining the prices of activities, is based on care complexity and logistic characteristic (two-factor structure). The second scale, knowledge regarding freelance-related characteristics, encompassed two domains: knowledge regarding administrative rules and pensions and retirement issues. CONCLUSIONS: The developed inventory showed adequate evidence of initial validity and reliability, useful for filling the gap given by the unavailability of valid assessments for educators who pursue measuring the nursing students' preparedness to undertake self-employed careers.

Ankrd31 in Sperm and Epididymal Integrity.

Ankyrin proteins (ANKRD) are key mediators linking membrane and sub-membranous cytoskeletal proteins. Recent findings have highlighted a new role of ANKRD31 during spermatogenesis, elucidating its involvement in meiotic recombination and male germ cell progression. Following testicular differentiation, spermatozoa (SPZ) enter into the epididymis, where they undergo several biochemical and enzymatic changes. The epididymal epithelium is characterized by cell-to-cell junctions that are able to form the blood-epididymal barrier (BEB). This intricate epithelial structure provides the optimal microenvironment needed for epididymal sperm maturation. To date, no notions have been reported regarding a putative role of ANKRD31 in correct BEB formation. In our work, we generated an Ankrd31 knockout male mouse model (Ankrd31-/- ) and characterized its reproductive phenotype. Ankrd31-/- mice were infertile and exhibited oligo-astheno-teratozoospermia (a low number of immotile SPZ with abnormal morphological features). In addition, a complete deregulation of BEB was found in Ankrd31-/- , due to cell-to-cell junction anomalies. In order to suggest that BEB deregulation may depend on Ankrd31 gene deletion, we showed the physical interaction among ANKRD31 and some epithelial junction proteins in wild-type (WT) epididymides. In conclusion, the current work shows a key role of ANKRD31 in the control of germ cell progression as well as sperm and epididymal integrity.

Multidimensional Statistical Technique for Interpreting the Spontaneous Breakthrough Cancer Pain Phenomenon. A Secondary Analysis from the IOPS-MS Study.

Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that "breaks through" a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) is a subtype of BTcP that occurs in the absence of any specific activity. Since NP-BTcP has an important clinical impact, this analysis is aimed at characterizing the NP-BTcP phenomenon through a multidimensional statistical technique. This is a secondary analysis based on the Italian Oncologic Pain multiSetting-Multicentric Survey (IOPS-MS). A correlation analysis was performed to characterize the NP-BTcP profile about its intensity, number of episodes per day, and type. The multiple correspondence analysis (MCA) determined the identification of four groups (phenotypes). A univariate analysis was performed to assess differences between the four phenotypes and selected covariates. The four phenotypes represent the hierarchical classification according to the status of NP-BTcP: from the best (phenotype 1) to the worst (phenotype 4). The univariate analysis found a significant association between the onset time >10 min in the phenotype 1 (37.3%)' vs. the onset > 10 min in phenotype 4 (25.8%) (p < 0.001). Phenotype 1 was characterized by the gastrointestinal type of cancer (26.4%) with respect to phenotype 4, where the most frequent cancer affected the lung (28.8%) (p < 0.001). Phenotype 4 was mainly managed with rapid-onset opioids, while in phenotype 1, many patients were treated with oral, subcutaneous, or intravenous morphine (56.4% and 44.4%, respectively; p = 0.008). The ability to characterize NP-BTcP can offer enormous benefits for the management of this serious aspect of cancer pain. Although requiring validation, this strategy can provide many indications for identifying the diagnostic and therapeutic gaps in NP-BTcP management.

CRISP2, CATSPER1 and PATE1 Expression in Human Asthenozoospermic Semen.

The etiology of human asthenozoospermia is multifactorial. The need to unveil molecular mechanisms underlying this state of infertility is, thus, impelling. Circular RNAs (circRNAs) are involved in microRNA (miRNA) inhibition by a sponge activity to protect mRNA targets. All together they form the competitive endogenous RNA network (ceRNET). Recently, we have identified differentially expressed circRNAs (DE-circRNAs) in normozoospermic and asthenozoospermic patients, associated with high-quality (A-spermatozoa) and low-quality (B-spermatozoa) sperm. Here, we carried out a differential analysis of CRISP2, CATSPER1 and PATE1 mRNA expression in good quality (A-spermatozoa) and low quality (B-spermatozoa) sperm fractions collected from both normozoospermic volunteers and asthenozoospermic patients. These sperm fractions are usually separated on the basis of morphology and motility parameters by a density gradient centrifugation. B-spermatozoa showed low levels of mRNAs. Thus, we identified the possible ceRNET responsible for regulating their expression by focusing on circTRIM2, circEPS15 and circRERE. With the idea that motility perturbations could be rooted in quantitative changes of transcripts in sperm, we evaluated circRNA and mRNA modulation in A-spermatozoa and B-spermatozoa after an oral amino acid supplementation known to improve sperm motility. The profiles of CRISP2, CATSPER1 and PATE1 proteins in the same fractions of sperm well matched with the transcript levels. Our data may strengthen the role of circRNAs in asthenozoospermia and shed light on the molecular pathways linked to sperm motility regulation.

A Call to Action by the Italian Mesotherapy Society on Scientific Research.

Mesotherapy (local intradermal therapy, LIT) is a technique used to slowly spread drugs in tissues underlying the site of injection to prolong the pharmacological effect with respect to intramuscular injection. Recommendations for proper medical use of this technique have been made for pain medicine and rehabilitation, chronic venous disease, sport medicine, musculoskeletal disorders, several dermatological conditions, skin ageing, and immune-prophylaxis. Although mesotherapy is considered a valid technique, unresolved questions remain, which should be answered to standardize methodology and dosing regimen as well as to define the right indications in clinical practice. New randomized controlled trials are needed to test single products (dose, frequency of administration, efficacy and safety). Even infiltration of substances for dermo-cosmetic purposes must be guided by safety and efficacy tests before being proposed by mesotherapy. In this article, we put forth a preclinical and clinical research plan and a health technology assessment as a call to action by doctors, researchers and scientific societies to aid national health authorities in considering mesotherapy for prevention, treatment and rehabilitation paths.

A Longitudinal Study of Breakthrough Cancer Pain: An Extension of IOPS-MS Study.

The aim of this study was to longitudinally assess the characteristics of background pain and breakthrough pain (BTcP), analgesic treatment, and satisfaction with treatment four weeks after the first assessment. METHODS: Adult cancer patients with a diagnosis of BTcP were included. At T0, age, gender, visit setting, cancer diagnosis, the extent of the disease, ongoing anticancer treatments, and Karnofsky level were recorded. The background pain intensity in the last 24 h (on a numerical scale 0-10), opioids used for background pain, and their doses, expressed as oral morphine equivalents (OME), as well as other analgesic drugs, were recorded. The number of BTcP episodes, their intensity, predictability and precipitating factors, onset duration of untreated episodes, and interference with daily activities were collected. Analgesics and doses used for BTcP, and the mean time to meaningful pain relief after taking medication, were assessed. The level of satisfaction with BTcP medication was also assessed. Adverse effects to be attributed to these medications were also recorded. At T4, the same data were evaluated. RESULTS: After one-month follow-up, patients had a lower number of BTcP episodes and peak intensity, possibly due to the optimization of background analgesia. The principal characteristics of BTcP did not change significantly. CONCLUSION: A careful and continuous assessment should be guaranteed to all patients to limit the burden induced by BTcP, other than treating BTcP episodes with short-onset opioids.

Oxycodone/Acetaminophen: The Tailoring Combination Treatment for Specific Clinical Profile of Opioid Well-Responsive Cancer Pain.

BACKGROUND: International guidelines recommend moderate-to-severe cancer pain to be treated with strong opioids. However, pain management remains an unsolved matter, at least in the demanding oncology and palliative care setting. Although cancer pain consists of multiple components, which interact in complex ways where combination therapy can better intercept multiple pain characteristics, few studies have used a non-opioid/opioid association to exploit possible synergistic actions. Even the efforts of a recent approach emphasizing appropriate pain assessment and accurate classification to obtain personalized pain management have not produced a satisfactory analgesic strategy. OBJECTIVE: This analysis was intended to evaluate the effectiveness of the immediate release fixed combination of oxycodone/acetaminophen (OxyIR/Par) for the treatment of moderate-to-severe intensity background pain used alone or in combination with other strong opioids in cancer patients with breakthrough cancer pain (BTcP). This is a secondary analysis of a wider observational, prospective, multicenter study [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] performed on 179 patients treated with opioids for cancer pain who received the fixed combination of oxycodone/acetaminophen (OxyIR/Par) for the treatment of background pain (BGP). RESULTS: Cancer patients with breakthrough cancer pain and controlled BGP (Background Pain) were classified according to the presence of analgesic therapy with tablets of fixed combination OxyIR/Par alone (group A, n=120) or tablets of fixed combination OxyIR/Par combined with other strong opioids (group B, n=59). Clinical features of group A were different to group B: higher mean Karnofsky Performance Status Index 70.3% (95% CI=67.2-73.5; median=70, CI=60-80) vs 58.3 (95% CI=53.4-63.2; median=50, CI=45-70) (P<0.001), and mainly group A patients were treated in an ambulatory setting (55.0% group A vs 33.9% group B) (p<0.001). Both groups had managed BGP with similar mean dosages (group A: 12.0, CI=10.5-13.4; group B: 13.1, CI=11.0-15.1) and frequencies of OxyIR/Par alone for group A and in association to other opioids for group B, but Breakthrough cancer Pain (BTcP) exhibited different characteristics in the two groups, showing a lower mean intensity numerical rating scale (NRS) of 7.5 (95% CI=7.2-7.7; median=7, CI=7-8 group A) vs 7.9 (95% CI=7.6, 8.2; median= 8, CI=7-9 group B) (P=0.04) and a higher percentage of patients had a faster onset, defined as the maximum intensity reached in less than 10 minutes, 81.7% (N=98) in group A vs 59.3% (n=35) in group B (P=0.002). CONCLUSION: This is the first analysis about the efficacy of an immediate-release fixed combination of OxyIR/Par in the real world for moderate-to-severe background cancer pain and breakthrough cancer pain. The oral fixed combination OxyIR/Par provided an adequate level of analgesia for moderate-severe background cancer pain, in a different cohort of cancer patients with different performance status, both in ambulatory and palliative settings. The low dosage of fixed combination OxyIR/Par was effective alone or in association with other opioids.

Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study.

PURPOSE: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. METHODS: Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use. RESULTS: Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients' cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy. CONCLUSION: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care.

Current pharmacological approaches to the treatment of tendinopathy.

INTRODUCTION: Tendinopathies are common in elite and recreational athletes: traditionally considered overuse injuries, they involve excessive tensile loading and subsequent breakdown of the loaded tendon. Many pharmacological treatments have been proposed for the management of tendinopathy, with no agreement regarding the overall best option available both for Achilles and patellar tendinopathy. AREAS COVERED: The present article reports the best scientific evidence regarding the efficacy and safety of different pharmacological treatments in different types of tendinopathy, focusing on Achilles and patellar tendinopathy, the conditions on which more studies have been published. EXPERT OPINION: No univocal evidence exists regarding the best non-operative management, which includes non-steroidal anti-inflammatory drugs, platelet-rich plasma, high volume image-guided injections, hyaluronic acid, and prolotherapy, for tendinopathy (in particular Achilles and patellar tendinopathies) as a suitable alternative to the commonly used eccentric loading rehabilitation regimen. It is unclear whether the combination of pharmacological substances with physical therapy would produce better results than physical therapy alone. There is an overall lack of published well-performed randomized controlled trials comparing the various options available for the management of tendinopathy, studying large cohorts of patients for adequately long follow-up periods and with well-validated standardized scores and scales.

Insights into the Role of Estrogen Receptor ß in Triple-Negative Breast Cancer.

Estrogen receptors (ERα and ERß) are ligand-activated transcription factors that play different roles in gene regulation and show both overlapping and specific tissue distribution patterns. ERß, contrary to the oncogenic ERα, has been shown to act as an oncosuppressor in several instances. However, while the tumor-promoting actions of ERα are well-known, the exact role of ERß in carcinogenesis and tumor progression is not yet fully understood. Indeed, to date, highly variable and even opposite effects have been ascribed to ERß in cancer, including for example both proliferative and growth-inhibitory actions. Recently ERß has been proposed as a potential target for cancer therapy, since it is expressed in a variety of breast cancers (BCs), including triple-negative ones (TNBCs). Because of the dependence of TNBCs on active cellular signaling, numerous studies have attempted to unravel the mechanism(s) behind ERß-regulated gene expression programs but the scenario has not been fully revealed. We comprehensively reviewed the current state of knowledge concerning ERß role in TNBC biology, focusing on the different signaling pathways and cellular processes regulated by this transcription factor, as they could be useful in identifying new diagnostic and therapeutic approaches for TNBC.

Careful Breakthrough Cancer Pain Treatment through Rapid-Onset Transmucosal Fentanyl Improves the Quality of Life in Cancer Patients: Results from the BEST Multicenter Study.

OBJECTIVES: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. METHODS: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Stable chronic background pain (numeric rating scale, NRS ≤ 4) during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). RESULTS: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (linear p-value = 0.1) and dyspnea (Linear p-value = 0.05). The ESAS and PSQI questionnaires confirmed these positive results (p < 0.0001 and p = 0.002, respectively). CONCLUSIONS: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance.

Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERß) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERß under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERß in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERß of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERß association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERß association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERß in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners.