Predicting postoperative hypocortisolism in patients with non-aldosterone-producing adrenocortical adenoma: a retrospective single-centre study.

BACKGROUND: Limited information exists on postoperative hypocortisolism and hypothalamus-pituitary-adrenal axis recovery in patients with adrenal incidentaloma following unilateral adrenalectomy. We evaluated frequency of postoperative hypocortisolism and predictors for recovery in non-aldosterone-producing adrenocortical adenoma patients after unilateral adrenalectomy. METHODS: A retrospective analysis of 32 adrenal incidentaloma patients originally included in the ITACA trial (NCT04127552) with confirmed non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy from September 2019 to April 2023 was conducted. Preoperative assessments included adrenal MRI, anthropometrics, evaluation of comorbidities, adrenal function assessed via ACTH, urinary free cortisol, and 1 mg dexamethasone suppression test. ACTH and serum cortisol or Short Synacthen test were performed within 6 days, 6 weeks, 6 months, and a year after surgery. RESULTS: Six days postoperative, 18.8% of patients had normal adrenal function. Among those with postoperative hypocortisolism, 53.8% recovered by 6 weeks. Patients with earlier adrenal recovery (6 weeks) had lower preoperative 1 mg dexamethasone suppression test (median 1 mg dexamethasone suppression test 76.2 [61.8-111.0] nmol/L vs 260.0 [113.0-288.5] nmol/L, p < 0.001). Univariate analysis showed preoperative 1 mg dexamethasone suppression test negatively related with baseline ACTH levels (r = - 0.376; p = 0.041) and negatively associated with the 6-week baseline (r = - 0.395, p = 0.034) and 30-min cortisol levels during Short Synacthen test (r = - 0.534, p = 0.023). Logistic regression analysis demonstrated preoperative 1 mg dexamethasone suppression test as the only biochemical predictor for 6-week adrenal recovery: ROC curve identified a 1 mg dexamethasone suppression test threshold of 131 nmol/L predicting 6-week recovery with 89.5% sensitivity and 72.7% specificity (AUC 0.87; 95% CI 66.9-98.7, p < 0.001). Other preoperative assessments (tumor size, ACTH levels and anthropometrics) were not associated with postoperative hypothalamus-pituitary-adrenal axis function, but the presence of diabetes was associated with a lower probability of recovery (OR = 24.55, p = 0.036). ACTH levels increased postoperatively in all patients but did not predict hypothalamus-pituitary-adrenal axis recovery. CONCLUSIONS: The preoperative 1 mg dexamethasone suppression test cortisol value and presence of diabetes are the only relevant predictor of hypothalamus-pituitary-adrenal axis recovery in patients with non-aldosterone- producing adrenocortical adenoma undergoing surgery, regardless other clinical and biochemical variables. Notably, pre- and postoperative ACTH levels did not predict hypothalamus-pituitary-adrenal axis recovery. These findings point towards the potential for saving resources by optimizing their allocation during follow-up assessments for patients with non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy.

Robotic resection of presacral tumors.

BACKGROUND: Presacral tumors are a rare entity typically treated with an open surgical approach. A limited number of minimally invasive resections have been described. The aim of the study is to evaluate the safety and efficacy of roboticresection of presacral tumors. METHODS: This is a retrospective single system analysis, conducted at a quaternary referral academic healthcare system, and included all patients who underwent a robotic excision of a presacral tumor between 2015 and 2023. Outcomes of interest were operative time, estimated blood loss, complications, length of stay, margin status, and recurrence rates. RESULTS: Sixteen patients (11 females and 5 males) were included. The median age of the cohort was 51 years (range 25-69 years). The median operative time was 197 min (range 98-802 min). The median estimated blood loss was 40 ml, ranging from 0 to 1800 ml, with one patient experiencing conversion to open surgery after uncontrolled hemorrhage. Urinary retention was the only postoperative complication that occurred in three patients (19%) and was solved within 30 days in all cases. The median length of stay was one day (range 1-6 days). The median follow-up was 6.7 months (range 1-110 months). All tumors were excised with appropriate margins, but one benign and one malignant tumor recurred (12.5%). Ten tumors were classified as congenital (one was malignant), two were mesenchymal (both malignant), and five were miscellaneous (one malignant). CONCLUSIONS: Robotic resection of select presacral pathology is feasible and safe. Further studies must be conducted to determine complication rates, outcomes, and long-term safety profiles.

Assessing robotic-assisted surgery versus open approach in penetrating Crohn's disease: advantages and outcomes in ileocolic resection.

INTRODUCTION: Penetrating Crohn's disease (CD) often necessitates surgical intervention, with the open approach traditionally favored. Robotic-assisted surgery offers potential benefits but remains understudied in this complex patient population. Additionally, the lack of standardized surgical complexity scoring in CD hinders research and comparisons. METHODS: We retrospectively analyzed adult patients with penetrating CD who underwent either robotic-assisted ileocolic resection (RICR) or open ileocolic resection (OICR) at our institution from January 2007 to December 2021. We assessed endpoints, including length of stay, complications, readmissions, reoperations, and other perioperative outcomes. RESULTS: RICR demonstrated safety outcomes comparable to OICR. Importantly, RICR patients experienced significantly reduced estimated blood loss (p < 0.0001), shorter hospital stays (median 4.5 days versus 6.9 days; p = 0.01), lower surgical site infection rates (0% versus 15.4%; p = 0.01), and decreased 30-day readmission rates (0% versus 15.4%; p = 0.01). Linear regression analysis revealed the need for additional strictureplasties (coefficient: 84.8; p = 0.008), colonic resections (coefficient: 41.7; p = 0.008), and estimated blood loss (coefficient: 0.07; p = 0.002) independently correlated with longer operative times). CONCLUSION: Robotic-assisted surgery appears to be a safe and potentially beneficial alternative for the surgical management of penetrating CD, offering advantages in perioperative outcomes reducing length of stay, blood loss, surgical site infection rates, and readmission rates. Further validation with larger cohorts is warranted.

Glucocorticoids and cognitive function: a walkthrough in endogenous and exogenous alterations.

PURPOSE: The hypothalamic-pituitary-adrenal (HPA) axis exerts many actions on the central nervous system (CNS) aside from stress regulation. Glucocorticoids (GCs) play an important role in affecting several cognitive functions through the effects on both glucocorticoid (GR) and mineralocorticoid receptors (MR). In this review, we aim to unravel the spectrum of cognitive dysfunction secondary to derangement of circulating levels of endogenous and exogenous glucocorticoids. METHODS: All relevant human prospective and retrospective studies published up to 2022 in PubMed reporting information on HPA disorders, GCs, and cognition were included. RESULTS: Cognitive impairment is commonly found in GC-related disorders. The main brain areas affected are the hippocampus and pre-frontal cortex, with memory being the most affected domain. Disease duration, circadian rhythm disruption, circulating GCs levels, and unbalanced MR/GR activation are all risk factors for cognitive decline in these patients, albeit with conflicting data among different conditions. Lack of normalization of cognitive dysfunction after treatment is potentially attributable to GC-dependent structural brain alterations, which can persist even after long-term remission. CONCLUSION: The recognition of cognitive deficits in patients with GC-related disorders is challenging, often delayed, or mistaken. Prompt recognition and treatment of underlying disease may be important to avoid a long-lasting impact on GC-sensitive areas of the brain. However, the resolution of hormonal imbalance is not always followed by complete recovery, suggesting irreversible adverse effects on the CNS, for which there are no specific treatments. Further studies are needed to find the mechanisms involved, which may eventually be targeted for treatment strategies.

Efficacy of laparoscopic Toupet fundoplication compared to endoscopic and surgical procedures for GERD treatment: a randomized trials network meta-analysis.

PURPOSE: We aim to review and quantitatively compare laparoscopic Toupet fundoplication (LTF), Nissen fundoplication (LNF), anterior partial fundoplication (APF), magnetic augmentation sphincter (MSA), radiofrequency ablation (RFA), transoral incisionless fundoplication (TIF), proton pump inhibitor (PPI), and placebo for the treatment of GERD. A number of meta-analyses compared the efficacy of surgical and endoscopic procedures for recalcitrant GERD, but considerable debate on the effectiveness of operative strategies remains. METHODS: A systematic review of MEDLINE databases, EMBASE, and Web of Science for randomized controlled trials (RCTs) comparing the aforementioned surgical and endoscopic GERD treatments was performed. Risk ratio and weighted mean difference were used as pooled effect size measures, whereas 95% credible intervals (CrI) were used to assess relative inference. RESULTS: Thirty-three RCTs were included. Surgical and endoscopic treatments have similar RR for heartburn, regurgitation, bloating. LTF has a lower RR of post-operative dysphagia when compared to APF (RR 3.3; Crl 1.4-7.1) and LNF (RR 2.5; Crl 1.3-4.4). The pooled network meta-analysis did not observe any significant improvement regarding LES pressure and pH < from baseline. LTF, APF, LNF, MSA, RFA, and TIF had have a similar post-operative PPI discontinuation rate. CONCLUSION: LTF has a lower rate of post-operative dysphagia when compared to APF and LNF. The pre-post effects, such as GERD-HQRL, LES pressure, and pH <4, should be avoided in meta-analyses because results may be biased. Last, a consensus about the evaluation of GERD treatments' efficacy and their outcomes is needed.

A comparison of surgical techniques for perineal wound closure following perineal excision: a systematic review and network meta-analysis.

BACKGROUND: To mitigate pelvic wound issues following perineal excision of rectal or anal cancer, a number of techniques have been suggested as an alternative to primary closure. These methods include the use of a biological/dual mesh, omentoplasty, muscle flap, and/or pelvic peritoneum closure. The aim of this network analysis was to compare all the available surgical techniques used in the attempt to mitigate issues associated with an empty pelvis. METHODS: An electronic systematic search using MEDLINE databases (PubMed), EMBASE, and Web of Science was performed (Last date of research was March 15th, 2023). Studies comparing at least two of the aforementioned surgical techniques for perineal wound reconstruction during abdominoperineal resection, pelvic exenteration, or extra levator abdominoperineal excision were included. The incidence of primary healing, complication, and/or reintervention for perineal wound were evaluated. In addition, the overall incidence of perineal hernia was assessed. RESULTS: Forty-five observational studies and five randomized controlled trials were eligible for inclusion reporting on 146,398 patients. All the surgical techniques had a comparable risk ratio (RR) in terms of primary outcomes. The pooled network analysis showed a lower RR for perineal wound infection when comparing primary closure (RR 0.53; Crl 0.33, 0.89) to muscle flap. The perineal wound dehiscence RR was lower when comparing both omentoplasty (RR 0.59; Crl 0.38, 0.95) and primary closure (RR 0.58; Crl 0.46, 0.77) to muscle flap. CONCLUSIONS: Surgical options for perineal wound closure have evolved significantly over the last few decades. There remains no clear consensus on the "best" option, and tailoring to the individual remains a critical factor.

A quantitative cholinergic and catecholaminergic 3D Atlas of the developing mouse brain.

The complex organization of brain regions during development requires a three-dimensional approach to facilitate the visualization and quantification of dynamic changes taking place throughout this important period. Using the tissue clearing method combined with immunohistochemistry, three-dimensional (3D) lightsheet microscopy and a multiresolution registration technique, we provide the first 3D atlases of the main cholinergic (CH) and catecholaminergic (CA) systems in the mouse brain from embryonic day 12 (E12) to post-natal day 8 (P8). We report that in several brain structures, there is a logarithmic scale increase of choline acetyltransferase and tyrosine hydroxylase positive neurons from E18 to P8. In addition, a detailed voxel-wise analysis revealed abrupt modifications in the developmental trajectory of many brain structures during the transition from E18 to P0. Our atlases will not only facilitate developmental studies aimed at quantitatively determining the fate of CH or CA neurons in utero but also be used as an anatomical reference to quantify other neuronal populations present in the annotated regions. In the future, these maps will be a reliable tool to study developmental malformations associated with neurological and psychiatric disorders.

Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial.

BACKGROUND: Oxaliplatin-based adjuvant chemotherapy is the standard treatment of high-risk colon cancer (CC). A shorter duration (3 months) can achieve a similar outcome [in terms of relapse-free survival (RFS)] to a longer duration. This study reports the overall survival (OS) analysis of the three or six colon adjuvant (TOSCA) phase III study. It assessed different adjuvant chemotherapy durations in patients with resected high-risk stage II and stage III CC. MATERIAL AND METHODS: TOSCA was an open-label, phase III, multicentre, non-inferiority trial conducted in 130 Italian centres. Patients were randomly assigned, in a 1 : 1 ratio, to receive 3 months of standard doses of FOLFOX/CAPOX, or 6 months of FOLFOX/CAPOX. Patients with histologically confirmed high-risk stage II and III CC were included, with RFS being the primary end point. OS was a secondary end point. RESULTS: From June 2007 to March 2013, 3759 patients were accrued. At a median follow-up of 7 years, the hazard ratio (HR) for RFS of the 3-month versus 6-month arms was 1.13; 95% confidence interval (CI) 0.99-1.29, P for non-inferiority = 0.380, P for superiority = 0.068, crossing the non-inferiority limit of 1.20. This result did not allow us to reject the null hypothesis of the inferiority of the 3-month arm. The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority = 0.288). At the last follow-up analysis, the absolute OS difference between arms was <1%. CONCLUSIONS: The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. The extra benefit provided by the longer treatment should be balanced against the extra toxicity of more prolonged therapy. The trial is registered with ClinicalTrials.gov, registration number: NCT0064660.

Effects of an individualized home-based unsupervised aerobic training on body composition and physiological parameters in obese adults are independent of gender.

PURPOSE: Evaluation of the effects of an individualized home-based unsupervised aerobic training on body composition, physical and physiological parameters in female and male obese adults. METHODS: Two hundred and twenty obese adults (age 47.9 ± 12.4 years; BMI 38.0 ± 7.2 kg/m2) entered the 4-month training program. Body composition, physiological and functional capacities were assessed pre- and post-intervention. All subjects were requested to perform unsupervised aerobic training with the intensity based on heart rate, walking speed and OMNI-RPE score corresponding to the individual ventilatory threshold for at least 5 days/week. RESULTS: After 4-month study period, 40% of patients completed the protocol, 24% had high compliance (HC) (exercise ≥ 3 days/week), while 16% had low compliance (LC) to exercise prescription (exercise < than 3 days/week). In HC group, a significant improvement of body composition variables after training was performed. Moreover, oxygen uptake and metabolic equivalent at peak significantly increased after training. Six-minute walking test (6MWT) distance significantly increased while heart rate during 6MWT was significantly lower after training. No significant differences were found in LC group between pre- and post-intervention in all variables. Interestingly, gender does not influence the effects of training. CONCLUSIONS: Our results indicate that subjects, independent of gender, with high compliance to the aerobic training based on a new individualized method can achieve a significant reduction in weight loss and also an improvement in physical and physiological parameters. This innovative personalized prescription could be a valuable tool for exercise physiologist, endocrinologists, and nutritionists to approach and correct life style of obese subjects.

A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. RESULTS: A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53-1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38-1.20, P = 0.181). Grade ≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). CONCLUSION: The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced. CLINICAL TRIAL NUMBER: EudraCT# 2011-002564-24.

Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial.

BACKGROUND: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy. MATERIALS AND METHODS: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). RESULTS: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. CONCLUSIONS: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy. CLINICAL TRIAL NUMBER: NCT01086826, www.clinicaltrials.gov.

Influence of treadmill training on bone structure under osteometabolic alteration in rats subjected to high-fat diet.

Nutrition and physical training have important roles in the accumulation and maintenance of bone mass. The aim of this study was to evaluate, in ovariectomized rats (OVX), the effects of treadmill training (T) with high-fat diet (F) on weight gain and bone tissue properties with eight groups (n = 10) for 12 weeks: OVX SC (OVX, sedentary lifestyle, diet control); OVX SF; OVX TC; OVX TF; SH SC (SHAM, sedentary lifestyle, diet control); SH SF; SH TC; and SH TF. Weekly weight gain and final body composition were assessed. After euthanasia, tibiae were analyzed. The trained animals had higher body weight (P = 0.001), bone mineral density (P < 0.001), and trabecular bone (P < 0.001). The animals with a high-fat diet showed higher global fat (P < 0.001), percentage of global fat (P < 0.001) and deformation at impact (P = 0.031) and reduced tibial bone mineral content (P = 0.036). Physical training improves bone microarchitecture, without presenting an increase in impact resistance, and a high-fat diet increases body fat and impairs bone mineralization.

Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.

BACKGROUND: Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. PATIENTS AND METHODS: TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. RESULTS: From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). CONCLUSIONS: TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT00646607.

A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study.

BACKGROUND: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. PATIENTS AND METHODS: Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. RESULTS: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). CONCLUSIONS: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. CLINICAL TRIAL NUMBER: NCT00753675.

Effects of Fitlight training on cognitive-motor performance in élite judo athletes.

Aims: The aims of this study were to verify if a 5-week cognitive-motor training (CMT) using FitlightsTM induced changes in young adult judo athletes compared to a non-intervention group. Specifically, it was verified if CMT influenced executive functions (EFs), physical fitness and brain-derived neurotrophic factor (BDNF) levels. Additionally, athletes' competitive results were compared between groups. Method: Twenty-seven athletes (14 males and 13 females; age = 19.5 ± 2.0 years) were assigned to the Fitlight (FG) and control (CG) groups which performed 5 weeks of CMT, respectively, including 25 min per day of Fitlight training or traditional judo practice. All participants performed cognitive (flanker task and forward/backward digit span) and fitness tests (counter movement jump, handgrip test, dynamic and isometric chin up). In addition, BDNF was collected by saliva sampling and competitive results after the intervention period were considered. Results: RM-ANOVA showed significant differences in FG for the accuracy of flanker (p = 0.028) and backward digit span (p < 0.001). Moreover, significant differences in FG were found for relative dynamic chin up (p = 0.027) and counter movement jump (p = 0.05). In addition, a significant difference in FG was found for competitive results after the intervention period (p < 0.01).No significant differences were found for BDNF and other cognitive and fitness measures (p > 0.05). Conclusion: A 5-week judo-specific CMT improved EFs and motor performance in élite judo athletes. It seems that CMT with Fitlight™ could be considered an additional support to coaches during the training period.

Generation of induced pluripotent stem cells (CSSi017-A)(12862) from an ALS patient carrying a repeat expansion in the C9orf72 gene.

Genetic expansions of the hexanucleotide repeats (GGGGCC) in the C9orf72 gene appear in approximately 40% of patients with familial ALS and 7% of patients with sporadic ALS in the European population, making this mutation one of the most prevalent genetic mutations in ALS. Here, we generated a human induced pluripotent stem cell (hiPSC) line from the dermal fibroblasts of a patient carrying a 56-repeat expansion in an ALS disease-causing allele of C9orf72. These iPSCs showed stable amplification in vitro with normal karyotype and high expression of pluripotent markers and differentiated spontaneously in vivo into three germ layers.

Induced pluripotent stem cell production (CSSi019-A)(14432) from an asymptomatic subject carrying a expansion of C9orf72 gene.

One of the genetic mutations most associated with the onset of amyotrophic lateral sclerosis, both in sporadic and familial cases, is the expansion of the C9orf72 gene. The presence of more than 30 repeats (GGGGCC) correlates with uncertain ALS symptomatology. Here we collected a dermal biopsy from a subject carrying 36 hexanucleotide repeats and reprogrammed it into an induced pluripotent stem cell line. Despite the number of repeat elements, the subject had no symptoms at the age of the biopsy (76 years), thus resulting in a healthy carrier of the mutation.

Screening elderly cancer patients for disabilities: evaluation of study of osteoporotic fractures (SOF) index and comprehensive geriatric assessment (CGA).

BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional tool aimed at detecting multiple age-related problems; the study of osteoporotic fractures (SOF) index is a 3-item instrument designed to measure frailty and pre-frailty status. The aim of this prospective cohort study was to evaluate the accuracy of the SOF index and CGA in predicting the disability status in elderly cancer patients. PATIENTS AND METHODS: Patients aged ≥ 70 years with a confirmed diagnosis of a solid or hematologic tumor underwent both CGA and SOF assessment. The sensitivity and specificity of SOF in determining the presence of frailty were analyzed using the CGA as the reference standard. The diagnostic accuracy of SOF < 80% was considered not acceptable. RESULTS: The study involved 400 patients aged ≥ 70 years (median age 77.2, range 70-97).The SOF and CGA classified, respectively, 33.2% and 31.8% of patients as fit, 67.8% and 68.2% as unfit. The SOF showed a sensibility and a specificity of 89.0 [95% confidence interval (CI) 84.7-92.5] and 81.1 (73.2-87.5) with an accuracy of 86.5 (82.8-89.7). The negative predictive value (NPV) was 103/133, i.e. 77.4% (95% CI 69.4-84.2). CONCLUSIONS: As the SOF proved to reach the end-point of our study, we support its use as a means of screening elderly cancer patients in everyday clinical practice.

Sorafenib in patients with Child-Pugh class A and B advanced hepatocellular carcinoma: a prospective feasibility analysis.

BACKGROUND: Sorafenib has shown survival benefits in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A liver function. There are few prospective data on sorafenib in patients with HCC and CP class B. PATIENTS AND METHODS: A consecutive prospective series of 300 patients with CP class A or B HCC were enrolled in a dual-phase trial to determine survival and safety data according to liver function (class A or B) in patients receiving oral sorafenib 800 mg daily. [Results of this study were presented in part at the ASCO 2012 Gastrointestinal Cancers Symposium, 19-21 January 2012. J Clin Oncol 2012; 30 (Suppl 4): abstract 306.] RESULTS: Overall progression-free survival (PFS), time to progression (TTP) and overall survival (OS) were 3.9, 4.1 and 9.1 months, respectively. For patients with CP class A versus B status, PFS was 4.3 versus 2.1 months, TTP was 4.2 versus 3.8 months and OS was 10.0 versus 3. 8 months. Extrahepatic spread was associated with worse outcomes but taken together with CP class, liver function played a greater role in reducing survival. Adverse events for the two CP groups were similar. CONCLUSION: Although patients with HCC and CP class B liver function have poorer outcomes than those with CP class A function, data suggest that patients with CP class B liver function can tolerate treatment and may still benefit from sorafenib.