Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).

BACKGROUND: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC. PATIENTS AND METHODS: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment naive advanced TC. They received ramucirumab, carboplatin and paclitaxel for 6 cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was ORR according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were PFS, OS and safety. Centralized radiologic review was performed. RESULTS: From 11/2018 to 06/2023, 52 patients were screened, 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. ECOG PS was 0 in 68.5%, 1 in 31.4% patients. At the present analysis carried out some months later the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95%CI 63.1-91.6]. At the centralized radiological review of 33/35 evaluable patients, ORR was 57.6% [95%CI 39.2-74.5]. After a median follow-up of 31.6 months, median PFS was 18.1 [95%CI 10.8-52.3] and median OS 43.8 [95%CI 31.9-NR] months. Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE≥G3. CONCLUSIONS: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC.

Gender-specific associations of appendicular muscle mass with BMD in elderly Italian subjects.

Currently used diagnostic measures for sarcopenia are based on the evaluation of appendicular skeletal muscle mass (ASMM) divided by height-squared (ASMMI). This study aimed to investigate the associations between different operational definitions of appendicular muscle mass and BMD at different skeletal sites in aging Italian men and women. In 1199 consecutive healthy Italian subjects, aged 55 years or more (854 women, age 64.2 ± 6.4 years and 165 men, age 65.3 ± 6.1 years), we measured BMD at the lumbar spine (LS-BMD), at femoral neck (FN-BMD),at total hip (TH-BMD), at total body (WB-BMD) and at the right hand (H-BMD) and body composition parameters [ASMM, ASMMI, ASMM/Weight, total lean mass and total fat mass by DXA]. In all subjects, we also measured sex hormones, 25-hydroxyvitamin D and bone turnover markers. In men, both ASMM and ASMMI were positively correlated with BMD at all sites, whereas in women, ASMM and ASMMI did not show any significant correlation with BMD. In men, multiple regression analyses showed that ASMM was positively associated (p < 0.01) with FN-BMD, TH-BMD and H-BMD; however, these associations were no longer present when lean mass was included. In women, both fat mass and lean mass were found positively associated with BMD at all sites. In conclusion, among the different operational measures of the ASMM, only ASMM was significantly associated with BMD in elderly men, but not in elderly women.

Gastric Bypass after multiple restrictive procedures: Roux-en-Y or One Anastomosis? A retrospective multicentric study.

OBJECTIVE: When restrictive surgery fails, conversion to more malabsorptive techniques is frequently proposed. The aim of this study is to evaluate the weight loss figures between Roux-en-Y Gastric Bypass (RYGB) and One Anastomosis Gastric Bypass (OAGB) in patients who have already undergone Multiple Restrictive Procedures (MRP). PATIENTS AND METHODS: All patients who underwent conversion of Laparoscopic Sleeve Gastrectomy (LSG) to RYGB or OAGB between 2010 and 2019 were retrospectively analyzed. Only patients who had conversion for Weight Regain (WR) or Insufficient Weight Loss (IWL) after both Laparoscopic Gastric Banding (LGB) and LSG entered the study population. Finally, 44 patients underwent conversion to RYGB, and 24 patients to OAGB. RESULTS: Concerning Excess Weight Loss (%EWL) at 3, 6, 12, 24 postoperative months, the results for RYGB were 33.7%, 47.95%, 61.8%, 61.8%, while for OAGB were 38.3%, 51.9%, 63.75%, 79.45%. A significant difference was recorded in favor of OAGB at 3 (p=0.03) and 24 (p=0.046) postoperative months. % EWL at 24 months in the case of IWL was 57.8% for RYGB, while for OAGB was 72.7% (p=0.047). No significant difference was found considering patients with WR (80.9% and 80.5%; p= 0.999). Patients with better results at 24 months after surgery had a significantly longer time between sleeve and bypass than those with a lower % EWL. CONCLUSIONS: The results of the present study seem to show that both techniques give good results at 24 months in patients who have undergone MRP. However, OAGB shows overall better results, particularly in patients with IWL.

Long-term results of laparoscopic gastric sleeve: the importance of follow-up adherence.

OBJECTIVE: This study was conducted to assess the long-term results of the Laparoscopic Sleeve Gastrectomy (LSG) in patients not compliant with follow-up, and in patients who completed a postoperative follow-up program. PATIENTS AND METHODS: The data concerning LSG patients operated from February 2011 to December 2013 were retrospectively reviewed basing on a single center database. The patients with complete long-term follow-up were scheduled in Group A, while patients who failed to attend controls for more than two years were scheduled in Group B. Long-term results (weight loss, comorbidity improvement and late complications) were compared between the two groups. RESULTS: The study population consisted of 285 patients. Of these, 101 had a complete follow-up with a mean duration of 71 ± 7.6 months (Group A). The remaining 184 patients (Group B) were not compliant with follow-up and, consequently, the mean duration of follow-up was 5.5 ± 7.3 months (p < 0.00001). A higher number of patients with insufficient weight loss was recorded in Group B with respect to Group A (78 vs. 23; p = 0.001). The number of patients with results below 25% EWL was significantly higher in Group B than in Group A (24 vs. 5; p = 0.04). In the long-term, the rate of patients with symptomatic reflux requiring medical treatment was two-fold higher in Group B than in Group A. CONCLUSIONS: The adherence to a long-term follow-up plan after LSG seems to decrease the number of patients experiencing insufficient weight loss and those at risk for developing a gastro-esophageal reflux disease.

Feasibility of transradial approach in a hub and spoke cath lab network.

AIM: Radial artery approach for coronary angiography presents advantages in terms of reduction of costs and complications. Opening a diagnostic-only cath lab is controversial in an era of interventional approach. The authors present the data of Carpi diagnostic-only cath lab (Spoke), satellite of the main cath lab situated in Modena (Hub) 20 Kms apart. METHODS: Between January 2004 and December 2007, 1496 coronary angiograms were performed. The indication was ischemic heart disease in 1197 cases (80%), dilated cardiomiopathy in other 165 cases (11%) and valvular heart disease in the remaining 134 patients (9%). The procedure was performed percutaneously via radial artery in 95% (N=1421) of the cases, via brachial artery in 1% (N=15) and via femoral artery in the remaining 4% (N=60) of patients. RESULTS: Among the 1197 patients undergoing coronary angiography for ischemic heart disease, an indication to medical therapy was given in 443 (37%), a surgical indication in 216 (18%) patients and an indication to percutaneous coronary intervention (PCI) in 538 (45%) cases. PCI was performed in the Hub centre the same day and via the same arterial approach of the diagnostic angiography, maintaining the sheath in situ during transport. In 6 patients only it was necessary to shift to a femoral approach. CONCLUSIONS: This model presents many advantages: 1) a cath lab in a peripheral hospital allows a early carrying out of the hemodynamic examination with reduction of hospital stay; 2) transport to the Hub centre cath lab is undertaken only in patients who really need PCI; 3) the PCI is feasible the same day of the diagnostic examination; 4) this model relieves the hub centre congestion, ensuring motivation and professional competence for personnel of peripheral hospital.

Allergic manifestations to local anaesthetic agents for dental anaesthesia in children: a review and proposal of a new algorithm.

AIM: The purpose of this review was to evaluate allergic manifestations to dental local anaesthetic (LA) in children and to propose an algorithm for the diagnosis of LA allergy, in order to minimise the number of children who are wrongly categorised as allergic. MATERIALS AND METHODS: A comprehensive literature survey was performed on LA allergy in children before a dental treatment. In proposing a diagnostic algorithm, evidences from literature have been integrated with personal experience. RESULTS: Data from literature showed that overall less than 1% of young patients tested for suspected LA have a positive subcutaneous test and have a positive diagnosis. A complete diagnostic procedure should include: clinical history reported by patients, objective medical records, results of skin tests and provocation test with the suspected drug. Patients with negative skin tests should perform a subcutaneous challenge, while patients with a positive skin test should be tested for a different unrelated LA. CONCLUSION: Allergy to LA is a rare condition. A complete diagnostic algorithm will allow to identify paediatric patients correctly.

"Acute abdomen": early laparoscopy or active laparotomic-laparoscopic observation?

BACKGROUND/AIMS: Acute abdomen accounts for 13-40% of all emergency surgical admissions. The aim of this prospective randomized controlled study was to examine the role of early laparoscopy in the management of acute abdomen compared with the more traditional active observation. METHODOLOGY: From July 1993 to August 2004, 522 patients consecutively, admitted with "acute abdomen", were randomized to either early laparoscopy (260 patients) (group 1) or active observation and non-invasive investigation (262 patients) (group 2). Baseline investigations included a full blood count, a pregnancy test in women of reproductive age, chest and/or abdominal radiograph if indicated clinically. RESULTS: Sixty-two patients in the laparoscopy group underwent a total of 116 radiological investigations compared with a total of 558 investigations in all patients in the observation group (P < 0.05). In the observation group 34.7% of patients remained without a clear diagnosis compared with 4.2% of patients in the early laparoscopic group (P < 0.0001). The morbidity rate was 1.1% in group 1 and 27% in group 2 (P < 0.0001). The duration of hospital stay was significantly shorter in group 1 (3.1 vs. 7.3 days) (P < 0.01). Eight patients in group 1 required readmission (total readmission 46 days) compared with 58 patients in group 2 who stayed a total of 201 days (P < 0.05). CONCLUSIONS: Early laparoscopy is valuable in the management of acute abdomen. It provides a significantly higher diagnostic accuracy and a better improvement in quality of life than the more traditional approach observation.

Effects of cholecystectomy (laparoscopic versus open) on PMN-elastase.

BACKGROUND/AIMS: Polymorphonuclear leukocytes (PMN) are well recognized as being the principal cells in inflammatory response reaction. During the surgical procedures there is a massive release of elastase (PMN-elastase) from the neutrophils, along with other proteinases. Therefore the measurement of the PMN-elastase might be a useful indicator of the degree of surgical trauma. Laparoscopic cholecystectomy (LC) is a so-called "mini-invasive" surgical procedure and on the basis of this consideration the aim of the present prospective, non-randomized study, is to examine (a) whether the serum levels of PMN-elastase concentration are modified and how, in patients undergoing LC compared to patients undergoing open cholecystectomy (OC), (b) whether these findings are indicative of an increased risk to develop infectious complications and therefore whether they are clinically significant. METHODOLOGY: Plasma granulocyte elastase was determined photometrically, using an immune-activation immunoassay, in 86 patients (42 patients underwent OC and 44 LC). The levels of C reactive protein (CRP), an acute phase protein, were measured using a competitive CRP ELISA kit. Blood samples were collected from all patients a day before operation and at days 1, 3, 6 and 12 after operation. We established a reference range for elastase by measuring the serum elastase concentration in 68 normal control patients without gallbladder cholelithiasis or other diseases. RESULTS: On day, 1, 3 and 6 after surgery, patients that underwent OC showed a significant increase (p < 0.05) in plasma elastase concentration, while it was almost unchanged in LC patients. The mean values of the serum CRP on p.o. days 1, 3 and 6 were also significantly lower in the LC group than those in OC group (p < 0.05). We recorded three cases (7.1%) of postoperative infections in the "open" group. The CRP concentration remained high for 1, 3 and 6 days and normalized 10-12 days after surgery while the PMN-elastase normalized after 13, 14 and 16 days. CONCLUSIONS: The peripheral leukocyte function may be better preserved after LC in comparison to OC. Laparoscopic surgery, associated with a small skin incision and the avoidance of open laparotomy, can thus minimize surgical stress, and provide more favorable postoperative conditions for patients. Indeed excessive and prolonged post-injury elevations of PMN-elastase and CRP are associated with increased morbidity. Moreover, the PMN-elastase is a more sensible marker of inflammation in comparison to the CRP.

Ocular surface temperature in patients with evaporative and aqueous-deficient dry eyes: a thermographic approach.

OBJECTIVE: In recent decades infrared thermography (IRT) has facilitated accurate quantitative measurements of the ocular surface temperature (OST), applying a non-invasive procedure. The objective of this work was to develop a procedure based on IRT, which allows characterizing of the cooling of the ocular surface of patients suffering from dry eye syndrome, and distinguishing among patients suffering from aqueous deficient dry eye (ADDE) and evaporative dry eyes (EDE). APPROACH: All patients examined (34 females and 4 males, 23-84 years) were divided into two groups according to their Schirmer I result (⩽ 7 mm for ADDE and > 7 mm for EDE), and the OST was recorded for 7 s at 30 Hz. For each acquisition, the temperatures of the central cornea (CC) as well as those of both temporal and nasal canthi were investigated. MAIN RESULTS: Findings showed that the maximum temperature variation (up to 0.75 ± 0.29 °C) was at the CC for both groups. Furthermore, patients suffering from EDE tended to have a higher initial OST than those with ADDE, explained by the greater quantity of the tear film, evenly distributed over the entire ocular surface, keeping the OST higher initially. Results also showed that EDE patients had an average cooling rate higher than those suffering from ADDE, confirming the excessive evaporation of the tear film. SIGNIFICANCE: Ocular thermography paves the way to become an effective tool for differentiating between the two different etiologies of dry eye syndrome.

[Parathyroidectomy: bilateral exploration of the neck vs minimally invasive radioguided treatment]. / Paratiroidectomia: esplorazione bilaterale del collo versus trattamento radio-guidato mini-invasivo.

AIM: In the therapy of primary hyperparathyroidism, the first surgical intervention, if efficacious, can remarkably reduce the incidence of persistence and relapses which are approximately about 5%. At present, the surgical approach of choice should involve the bilateral exploration of the neck. METHODS: In the light of the high sensibility (91%) and specificity (98.8%) in the localization of parathyroid adenomas obtained by the parathyroid 99mTc-MIBI scintigraphy, we submitted, prospective and at random, between January 2001 and July 2004, 69 patients with primary hyperparathyroidism, to a conventional surgical treatment (bilateral exploration of the neck: 35 patients) or minimally-invasive approach (minimally invasive radioguided parathyroidectomy: 34 patients). This method consists of the injection of 50 mCi of 99mTc Sestamibi 2 h before the operation and the execution of parathyroid scintigraphy. When the adenoma is evident, we perform an incision of about 4 cm in the neck, 2 cm over the jugulum and the surgical dissection is guided by a probe showing the emission of gamma rays. RESULTS: The parameters considered in order to compare the 2 groups, i.e. operating time, hospital stay and time of recovery were reduced in a significant way in the group submitted to the minimally invasive radioguided parathyroidectomy (MIRP). There were no complications in the 2 groups. In the follow-up we did not observe cases of persistence or relapses. CONCLUSIONS: Therefore, we can confirm that the minimally invasive radioguided parathyroidectomy is a safe and efficacious method as well as the bilateral exploration of the neck. Moreover, cost reduction may convince many surgeons to consider MIRP the <> in the management of primary hyperparathyroidism.

Dynamic wetting: status and prospective of single particle based experiments and simulations.

The fundamental molecular and microscopic properties of materials leading to dynamic wetting and relaxation effects have been subject to numerous studies in the past decades, but a thorough understanding is still missing. While most previous experiments utilize fluids deposited on planar substrates, this article focuses on an attractive alternative based on single colloidal particles: colloidal particles have the ability to strongly interact with fluid-fluid interfaces and the behavior strongly depends on the surface properties of the particles and the fluids used. Recent progress in the manipulation and synthesis of colloidal particles with well-defined surface properties and shapes makes them ideal candidates to probe the fundamental surface properties leading to dynamic wetting effects. In this paper we review and discuss the status of experimental and numerical techniques to characterize the dynamic wetting of single particles at fluid-fluid interfaces, with the aim to assist scientists and engineers in the design of new experimental techniques and particle-based (bio)analytical tools.

Magnetic Resonance-compatible needle-like probe based on Bragg grating technology for measuring temperature during Laser Ablation.

Temperature monitoring in tissue undergone Laser Ablation (LA) may be particularly beneficial to optimize treatment outcome. Among many techniques, fiber Bragg grating (FBG) sensors show valuable characteristics for temperature monitoring in this medical scenario: good sensitivity and accuracy, and immunity from electromagnetic interferences. Their main drawback is the sensitivity to strain, which can entail measurement error for respiratory and patient movements. The aims of this work are the design, the manufacturing and the characterization of a needle-like probe which houses 4 FBGs. Three FBGs have sensitive length of 1 mm and are used as temperature sensors; one FBG with length of 10 mm is used as reference and to sense eventual strain. The optical fiber housing the FBGs was encapsulated within a needle routinely used in clinical practice to perform MRI-guided biopsy. Two materials were used for the encapsulation: i) thermal paste for the 3 FBGs used for temperature monitoring, to maximize the thermal exchange with the needle; ii) epoxy resin for the reference FBG, to improve its sensitivity to strain. The static calibration of the needle-like probe was performed to estimate the thermal sensitivity of each FBG; the step response was investigated to estimate the response time. FBGs 1 mm long have thermal sensitivity of 0.01 nm·°C(-1), whereas the reference FBG presents 0.02 nm·°C(-1). For all FBGs, the response time was in the order of 100 ms. Lastly, experiments were performed on ex vivo swine liver undergoing LA to i) evaluate the possible presence of measurement artifact, due to the direct absorption of laser light by the needle and ii) assess the feasibility of the probe in a quasi clinical scenario.

[Treatment with indobufen of platelet hyperaggregation in a group of patients with vascular diseases]. / Il trattamento con indobufene dell'iperaggregazione piastrinica in un gruppo di pazienti affetti da patologie vascolari.

Twenty-five patients with enhanced spontaneous platelet aggregation and impaired arterial or venous circulation syndromes have been treated by indobufen. Each of them received, by oral administration, 200 mg of the drug twice a day for periods of time from fifty one to hundred eleven days. This treatment normalized, in all the cases, the platelet aggregation. In eight patients of the group, three hours after the last drug administration, the average of the maximum platelet aggregation curves deflections, induced by ADP, epinephrine, ristocetin and collagen, resulted significantly reduced, while, in seven other patients, twelve hours after the last drug administration, only the aggregation curves induced by ADP and epinephrine resulted significantly inhibited. Most on the patients with arterial impairment syndromes noticed some improvements of their symptoms. Also the patients with light subjective post-phlebitic symptoms declared to feel better. The drug has been well tolerated. Therefore, its use is recommendable whenever it is advisable to get a full antiplatelet effect whose the prompt reversion might be required.

Mechanical ventilation with heated humidifiers: measurements of condensed water mass within the breathing circuit according to ventilatory settings.

Heated wire humidifiers (HWHs) are widely used to heat and humidify gases during mechanical ventilation. The control strategy implemented on commercial HWHs, based on maintaining constant gas temperature at the chamber outlet, shows weaknesses: humidifying performances depend on environmental temperature and ventilatory settings, and often condensation occurs. Herein, we analyzed in vitro HWH performances focusing on the condensation amount according to ventilatory settings. We used a physical model to define the parameters which mainly influence the HWH performances. In order to investigate the influence of minute volume (MV) and frequency rate (fr) on condensation, the other influencing parameters were kept constant during experiments, and we introduced a novel approach to estimate the condensation. The method, based on measuring the condensed vapor mass (Δm), provided more objective information than the visual-based scale used in previous studies. Thanks to both the control of other influencing factors and the accurate Δm measures, the investigation showed the Δm increase with MV and fr. Substantial condensation after 7 h of ventilation and the influence of MV and fr on Δm (i.e., Δm = 3 g at MV = 1.5 L min(-1) and fr = 8 bpm and Δm = 9.4 g at MV = 8 L min(-1) and fr = 20 bpm) confirm the weaknesses of `single-point temperature' control strategies.

Neurological and functional outcome in traumatic central cord syndrome.

STUDY DESIGN: Retrospective analysis of in-patient stay and prospective follow-up. OBJECTIVES: To study neurological and functional outcomes after traumatic central cord syndrome (TCCS). SETTING: Regional Spinal Unit of Florence, Italy. METHODS: In total, 82 patients, admitted for acute rehabilitation to our Centre (1996-2002) with a diagnosis of TCCS entered the study. Data on admission and discharge were collected for assessments performed at 18 months of injury or later. Data included: cause of injury, gender, type of vertebral lesion, treatment, time of hospitalisation (LoS), ASIA/ISCOS Impairment Scale, neurological examination, functional independence measure (FIM) on admission and discharge. Additional measures included the walking index for spinal cord injuries (WISCI), bladder management, FIM, spasticity on discharge/follow-up and neuropathic pain at follow-up. Correlations were performed on outcome measures in relation to age, treatment, LoS, spasticity and neuropathic pain. RESULTS: Average age was 52 (16-82) years. Causes included falls (47%), road traffic accidents (36%) and sport (7%). Of patients, 45% were treated surgically and 55% conservatively. LoS was 120 days (24-390), but less for those treated without surgery. Patients under 65 years had better outcomes with less neuropathic pain. Neurological and functional recovery was observed on discharge from rehabilitation, which continued in the period following discharge. Spasticity was equally present in all age groups. No difference in outcome was found as a result of spine surgery. CONCLUSIONS: Patients with TCCS are older than other spinal cord injured patients, but often show improvement after discharge. Improvement in subjects under 65 years was significantly better than for those over 65 years.

Possible correlations of ocular blood flow parameters with intraocular pressure and visual-field alterations in glaucoma: a study by means of color Doppler imaging.

The authors evaluated, by means of color Doppler imaging, the blood flow of the ophthalmic artery, ciliary arteries and central retinal artery in normal and glaucomatous subjects. In normals they found that flow velocities of all considered vessels progressively decline while resistivity indices increase with advancing age. In glaucomatous subjects there was a statistically significant reduction of the mean systolic peak flow velocity of the ophthalmic artery in comparison with normals. Glaucomatous eyes with uncontrolled IOP and with visual-field worsening showed a statistically significant decrease in the end-diastolic flow velocities and an increase in the resistivity index values in ciliary arteries.