Survey on the interest and commitment of AIFM members to scientific activities (SicAS) - The initiative of the FutuRuS working group.

PURPOSE: The "FutuRuS" working group of the Italian Association of Medical Physics and Health Physics (AIFM) designed a survey (SicAS) to get feedback from its members regarding their interests and their experience in taking part in scientific activities and events, with the objective of focusing future efforts of the AIFM towards increasing the scientific activity of the medical physics expert (MPE). METHODS: SicAS was sent out in March 2022 to all AIFM members by newsletter and official communication. SicAS was structured into three sections: personal information and institution of affiliation information, involvement in scientific activities, interest in and commitment to scientific activities. Responses were collected in a fully anonymised mode from the Google Forms platform and analysed with descriptive statistics. RESULTS: Out of 1289 members (active at the end of 2021), 467 responded to the Survey (response rate of 36%). The Survey results highlighted that AIFM members ranked the involvement of the MPE in scientific activities as highly relevant to the profession. However, 34.7% indicated devoting less than 10% of their working time to scientific activities. 67.5% of the respondents were dissatisfied with the time spent on scientific activities. The primary barrier was the lack of time (77%), followed by a lack of mentoring (32%). CONCLUSIONS: SicAS highlighted the need for AIFM initiatives to support members' scientific activities. National societies should help develop and support networks between members, create links among universities, hospitals, research institutions and industries, and provide guidelines and learning platforms for enhancing the MPEs' involvement in scientific activities.

Strengthening preparedness against global health threats: A paradigm shift based on One Health approaches.

The implementation of preparedness strategies to prevent and mitigate the impact of global health threats poses several challenges. It should promptly identify cross-cutting drivers of pandemic threats, assess context-specific risks, engage multiple stakeholders, and translate complex data from multiple sources into accessible information for action. This requires a coordinated, multidisciplinary and multisectoral effort engaging systems that, most of the time, work in isolation. The One Health (OH) approach promotes the collaboration and communication among different disciplines and sectors, and could be applied across the preparedness phases at national and international level. We discuss here gaps and needs in preparedness strategies, which can benefit from the OH approach, and a set of actionable recommendations, as shared with the G20-2021 with a dedicated Policy Brief. The discussion adds to the current debate about OH operationalization and promotes a paradigm shift towards coordinated prevention and preparedness strategies for early assessment and management of global health threats.

A rare case of Clostridium paraputrificum bacteremia in a 78-year-old Caucasian man diagnosed with an intestinal neoplasm.

Clostridium like species, particularly Clostridium perfrigens, are the second most common causes of human anaerobic infections, including myonecrosis and bacteremia. Clostridium paraputrificum is an infrequent isolate, which has been identified in only 1% of reported cases of clostridial infections. We herein report a rare case of C. paraputrificum bacteremia in a 78-year-old Caucasian man diagnosed with an intestinal carcinoma and liver neoplastic lesions. The isolate was susceptible to chloramphenicol, meropenem, metronidazole, vancomycin, and resistant to clindamycin and penicillin, and the patient was successfully treated with metronidazole. Malignancy and inflammatory bowel diseases are often associated with clostridial bacteremia, which cannot be neglected.

Antithymocyte globulin induction therapy in heart transplantation: prospective randomized study of high vs standard dosage.

BACKGROUND: In cardiac transplantation, high-dose antithymocyte globulin (ATG) induction therapy as short-term rejection prophylaxis has not been used. OBJECTIVE: To evaluate the efficacy and safety of intraoperative use of single high-dose ATG induction therapy after heart transplantation. PATIENTS AND METHODS: Fourteen patients received single high-dose ATG therapy plus shortened standard therapy (group1), and 16 patients received ATG standard therapy (group2). RESULTS: No perioperative deaths were reported. During follow-up, 3 deaths were recorded. Five-year patient survival was 92.8% in groupl vs 85.7% in group2 (P = .34). The mean (SD) number of acute rejection episodes per patient was 2.5 (2.2) in the high-dose ATG group vs 2.7 (2.5) in the standard therapy group (P = .83), with 5-year freedom from acute rejection of 45.5% in group 1 vs 35.6% in group 2 (P = .85). Infections were observed in 6 patients in group1 and in 8 patients in group2 (P = .69). Malignant disease was diagnosed in 1 patient in the high-dose group and 3 patients in the standard therapy group (P = .35). Chronic allograft vasculopathy was recognized in 4 patients (28%) in group1 and 8 (50%) in group2 (P = .05). Five-year actuarial freedom from allograft vasculopathy was 69.2% in the high-dose ATG group vs 50.0%% in the standard therapy group (P = .35). CONCLUSIONS: High-dose ATG for prevention of rejection episodes is safe and efficacious, with a lower rate of early and late complications, in particular, graft vasculopathy.

An EORTC phase I study of Bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer.

The combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4) is still a reference regimen in advanced colorectal cancer; however, the addition of new biologic compounds represents a significant way forward. Bortezomib is an inhibitor of proteasome, a multicatalytic enzyme complex that degrades several intracellular proteins. In this study, escalating doses of Bortezomib were administered along with the standard FOLFOX-4 doses, in order to evaluate the dose-limiting toxicity (DLT), toxicity profile and activity of the combination. Patients with advanced colorectal cancer, unpretreated for metastatic disease, were enroled in the study. Bortezomib starting dose was 1.3mg/m(2), which was to be escalated in the subsequent steps according to the toxicities observed after first cycle. Exploratory pharmacogenetics research was conducted by analysing the association between clinical outcomes and polymorphisms in candidate genes for response to each of the used drugs. Correlation between tumour marker changes and response was also investigated. One mg/m(2) (DL-1) was defined as being the maximum tolerated dose since only 1 DLT was observed in 6 patients. The main toxicities were haematologic, neuropathy, diarrhoea and fatigue. Amongst 13 evaluable patients, five had a partial response, five had a stable disease and three patients progressed. Two patients are long-term survivors after a combined chemosurgical approach. Further trials of the current combination may be justified.

The ubiquitin-proteasome system as a molecular target in solid tumors: an update on bortezomib.

The ubiquitin-proteasome system has become a promising molecular target in cancer therapy due to its critical role in cellular protein degradation, interaction with cell cycle and apoptosis regulation, and unique mechanism of action. Bortezomib (PS-341) is a potent and specific reversible proteasome inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies. In preclinical studies, bortezomib induced apoptosis of malignant cells through the inhibition of NF-|B and stabilization of pro-apoptotic proteins. Bortezomib also promotes chemo- and radiosensitization of malignant cells in vitro and inhibits tumor growth in murine xenograft models. The proteasome has been established as a relevant target in hematologic malignancies and bortezomib has been approved for the treatment of multiple myeloma. This review summarizes recent data from clinical trials in solid tumors.

Eosinophilic esophagitis is a component of the anticonvulsant hypersensitivity syndrome: description of two cases.

Anticonvulsant hypersensitivity syndrome is a rare syndrome caused by a specific, severe unusual reaction to antiepileptic agents; anticonvulsant hypersensitivity syndrome develops 1 week to 3 months after the introduction of the drug and most frequently consists of a multisystemic and multiorgan involvement. Drug withdrawal usually leads to rapid improvement of symptoms. Up to now no oesophageal damage has been described. We present two cases of carbamazepine hypersensitivity syndrome with concomitant development of eosinophilic oesophagitis that resolved after drug withdrawal.

No difference between supine and prone position for ERCP in conscious sedated patients: a prospective randomized study.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is usually performed with the patient prone or in the left lateral position. The supine position could be more comfortable and may facilitate airway management. On the other hand, technical difficulties and a greater risk of adverse cardiorespiratory events have been shown when ERCP is performed in a supine patient. Our aim was to assess, in a tertiary referral center, the differences between performing ERCP with the patient supine or prone, in terms of technical features and complications both during and after the procedure. PATIENTS AND METHODS: Between December 2005 and May 2006, 120 patients (66 female, mean age 62 years) who had an intact papilla and were candidates for therapeutic ERCP were prospectively randomized to undergo ERCP under conscious sedation with midazolam, in the prone (n = 60) or supine (n = 60) position, by an expert endoscopist (tutor) or a trainee. The following parameters were recorded: difficulty of cannulation and difficulty of ECRP procedure, time needed to visualize the papilla, time needed to achieve opacification and cannulation, exam duration, episodes of tachy/bradycardia and desaturation, episodes of duodenoscope displacement into the stomach, and complications. RESULTS: Ninety-eight patients underwent ERCP for benign disease and 22 for malignant biliary strictures. The ERCP success rate was 98.3 % in the tutor group and 43.3 % in the trainee group. No significant differences were found between the two groups of operators (tutors and trainees) in the recorded parameters and complication rates encountered in prone versus supine patients. CONCLUSION: Our results show that ERCP success rates and complications (intraoperative and postoperative) are similar whether ERCP is performed with the patient prone or supine, even when operators are of differing skill levels. Training, technique, and a proper learning phase are recommended in order to perform ERCP with no differences whether the patient is prone or supine.

Therapy of metastatic bladder carcinoma.

The methotrexate, vinblastine, doxorubicin, cisplatin (M-VAC) regimen has been considered as standard treatment of metastatic bladder carcinoma till recent years. The superiority of M-VAC both to cisplatin alone and to another cisplatin combination regimen has been demonstrated in randomized studies. During the last years, the use of gemcitabine in metastatic bladder carcinoma has considerably increased, mainly in combination with cisplatin (CG). A phase III trial comparing M-VAC and CG demonstrated similar activity and less toxicity for CG, which has now become the new standard of care for patients with metastatic bladder carcinoma. The substitution of cisplatin with carboplatin, the combination of platinum and taxanes, and the addition of a third drug to basal CG combination represent possible ways to improve outcome. Among the novel cytotoxic compounds, pemetrexed has raised interest, since a phase II second-line study showed a 28% response rate with a manageable toxicity profile. Vinflunine is a novel antitubulin agent with a relevant clinical activity in pretreated metastatic bladder carcinoma (18% response rate, 6.6 months median survival). Novel biologic compounds (in particular drugs targeting epidermal growth factor receptor) are being tested in metastatic bladder carcinoma also and much effort is being pursued in understanding the determinants of tumor response. Crucial mutations to which the tumor becomes addicted have to be discovered so that more effective and specific drugs or combinations can be delivered.

Wireless capsule endoscopy in the diagnostic of small intestine angiodysplasia in chronic uremic patient.

Gastroenteric bleeding due to angiodysplasia (AD) is a relatively common occurrence in patients with end-stage renal failure. Gastric and colon angiodysplasic lesions can be easily revealed by endoscopic procedures, whereas lesions of the small intestine are more difficult to detect. Imaging modalities used in the diagnostic imaging algorithm for the detection of small-bowel AD, include non-invasive methods like enema-helical computer tomography,(99m)Tc-labelled red blood cell scintigraphy, and angiography, and invasive methods such as intraoperative enteroscopy. We report the cases of 3 hemodialysis patients with recurrent episodes of gastrointestinal bleeding, caused by small-bowel AD diagnosed by means of wireless-capsule endoscopy. In all cases, previous gastroscopy and colonoscopy were unrevealing. Wireless-capsule endoscopy consists in swallowing a capsule endoscope (11 mmx27 mm) which contains a miniature video camera, a light source, batteries, and a radio transmitter. Video images are transmitted by means of radio telemetry to aerials taped to the body that allow images to be captured. Moving images from a period as long as 6 h are stored on a portable recorder. Wireless-capsule endoscopy may prove valuable in the assessment of gastrointestinal bleeding in uremic patients with unrevealing results at gastroscopy and colonoscopy.

[Angiodysplasia of the small bowel: a possible cause of anemia even in mild chronic renal failure]. / Angiodisplasia dell'intestino tenue: una possibile causa di anemizzazione nell'IRC anche di grado lieve.

BACKGROUND: Gastroenteric angiodysplasia (AD) is a vascular lesion characterized by vascular ectasias to the submucous sheath of the gastrointestinal tract. Lesions can be flat or raised, isolated or grouped and can break or ulcerate causing acute hemorrhage or, more commonly, chronic bleeding. CASE-REPORT: We describe a 65-year-old patient with a 3-yr history of chronic renal failure (CRF), who gradually developed anemia (hemoglobin (Hb) 10 g/dl) without any episodes of clinically relevant bleeding or any exposure to bleeding risk factors. Blood pressure (BP) was normal and renal function was stable (serum creatinine (Cr) 1.9 mg/dl). Routine laboratory tests showed a slight reduction in serum iron and transferrin saturation and a slightly elevated absolute reticulocyte count. These findings were associated with a positive occult gastrointestinal blood test and raised the clinical suspicion of chronic gastrointestinal blood loss. Oesophagogastro-duodenoscopy and colonoscopy demonstrated an absence of significant lesions, suggesting the need to investigate for a lesion localized in the small intestine. Capsular endoscopy, a recently developed endoscopic technique, particularly suited for small bowel pathology, was performed, and demonstrated the presence of an angiodysplasic lesion, located in the jejunum. CONCLUSIONS: Our case report supports the necessity for a complete clinical and laboratory evaluation of the possible causes of anemia superimposed on relative erythropoietin deficiency in CRF patients. When gastrointestinal blood loss is suspected, the entire gastroenteric tract should be examined to search for the bleeding sites. Our report also demonstrates that AD could be responsible for gastrointestinal bleeding even in mild CRF and not only, as usually reported, in end-stage renal disease (ESRD). Capsular endoscopy offers the unique possibility to determine the bleeding site in the small intestine and appears as an effective diagnostic procedure in CRF patients.

Role of antibiotic sensitivity testing before first-line Helicobacter pylori eradication treatments.

BACKGROUND: The resistance of Helicobacter pylori to antibiotics has been advocated as a major cause of treatment failure, and antimicrobial sensitivity testing has been proposed to improve efficacy; however, its role before first-line therapy has not been investigated in detail. AIM: To assess whether antimicrobial sensitivity testing improves the eradication rate of first-line anti-Helicobacter treatments and to compare the effectiveness of ranitidine bismuth citrate and omeprazole in the presence of H. pylori resistance to antibiotics. METHODS: Two hundred and forty-two patients were assigned to either empirical or antimicrobial sensitivity testing-based treatment; within each group, subjects were further randomized to receive ranitidine bismuth citrate, 400 mg b.d., tinidazole, 500 mg b.d., and clarithromycin, 500 mg b.d., or omeprazole, 20 mg b.d., clarithromycin, 500 mg b.d., and amoxicillin, 1 g b.d., for 1 week, with substitution of the resistant antibiotic in the antimicrobial sensitivity testing-based treatment group. RESULTS: Eradication rates were 67% [confidence interval (CI), 55-79%] in the empirical treatment group and 76% (CI, 65-87%) in the antimicrobial sensitivity testing-based group (P=N.S.). The overall success rate was 60% (CI, 51-69%) with omeprazole and 82% (CI, 73-91%) with ranitidine bismuth citrate (P<0.03); the latter overcame antibiotic resistance in 12 of 15 strains vs. zero of eight strains by omeprazole. CONCLUSIONS: Antimicrobial sensitivity testing before first-line treatment does not improve the eradication rate, which is greater when ranitidine bismuth citrate is included in the treatment.

The TB structural genomics consortium: a resource for Mycobacterium tuberculosis biology.

The TB Structural Genomics Consortium is an organization devoted to encouraging, coordinating, and facilitating the determination and analysis of structures of proteins from Mycobacterium tuberculosis. The Consortium members hope to work together with other M. tuberculosis researchers to identify M. tuberculosis proteins for which structural information could provide important biological information, to analyze and interpret structures of M. tuberculosis proteins, and to work collaboratively to test ideas about M. tuberculosis protein function that are suggested by structure or related to structural information. This review describes the TB Structural Genomics Consortium and some of the proteins for which the Consortium is in the progress of determining three-dimensional structures.

Second-line chemotherapy with a hybrid-alternating regimen of bolus 5FU modulated by methotrexate and infusional 5FU modulated by folinic acid in patients with metastatic colorectal cancer pretreated with 5FU. A phase 2 study.

BACKGROUND AND AIM: In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations. RESULTS: 34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03-7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8-21.9). Toxicity was mild. CONCLUSIONS: The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.

Transcriptional regulation of furA and katG upon oxidative stress in Mycobacterium smegmatis.

The DNA region upstream of katG in Mycobacterium smegmatis was cloned and sequenced. The furA gene, highly homologous to Mycobacterium tuberculosis furA, mapped in this region. The furA-katG organization appears to be conserved among several mycobacteria. The transcription pattern of furA and katG in M. smegmatis upon oxidative stress was analyzed by Northern blotting and primer extension. Although transcription of both furA and katG was induced upon oxidative stress, transcripts covering both genes could not be identified either by Northern blotting or by reverse transcriptase PCR. Specific transcripts and 5' ends were identified for furA and katG, respectively. By cloning M. smegmatis and M. tuberculosis DNA regions upstream of a reporter gene, we demonstrated the presence of two promoters, pfurA, located immediately upstream of the furA gene, and pkatG, located within the terminal part of the furA coding sequence. Transcription from pfurA was induced upon oxidative stress. A 23-bp sequence overlapping the pfurA -35 region is highly conserved among mycobacteria and streptomycetes and might be involved in controlling pfurA activity. Transcription from a cloned pkatG, lacking the upstream pfurA region, was not induced upon oxidative stress, suggesting a cis-acting regulatory role of this region.

Evidence-based risk assessment.

A knowledge framework for medical manual revision, competitive underwriting, accurate risk assessment, and precision decision making.

Hemodynamic performance of stented and stentless aortic bioprostheses.

BACKGROUND: This study compares the hemodynamic performance of stented and stentless bioprostheses used for aortic valve replacement in patients with aortic stenosis and small aortic root. METHODS: Between 1995 and 1998, 37 patients with a 21-mm aortic annulus (group 1) underwent aortic valve replacement with either a 21-mm Edwards Perimount or a 23-mm St. Jude Toronto bioprosthesis whereas 47 patients with a 23-mm aortic annulus (group 2) received either a 23-mm Medtronic Mosaic or a 25-mm Edwards Prima bioprosthesis. In each group mean and peak gradients, effective orifice area index, and left ventricular mass index were compared during follow-up. RESULTS: Group 1 patients showed a significant reduction of mean (p < 0.001) and peak gradients (p = 0.001) during follow-up, more evident for St. Jude Toronto versus Edwards Perimount (p = 0.02 and p = 0.05, respectively). Group 2 patients showed a significant reduction of mean and peak gradients (p < 0.001), more evident for Edwards Prima versus Medtronic Mosaic (p < 0.001 and p = 0.07, respectively). Effective orifice area index significantly increased only in group 1 (p = 0.005). Left ventricular mass index significantly decreased in all patients regardless of the type of valve (p < 0.001). Patients with Edwards Prima showed a trend to a higher regression of left ventricular mass index versus Medtronic Mosaic recipients (p = 0.07). CONCLUSIONS: After aortic valve replacement, stented and stentless bioprostheses exhibited similar results with a more evident hemodynamic improvement during follow-up in the stentless valves. Stented bioprostheses of new generation, however, may parallel the hemodynamic performance of stentless valves and appear to be a valid alternative for aortic valve replacement in elderly patients with a small aortic annulus.

Dissection of atrial septum after mitral valve replacement.

We report a patient who presented with paraprosthetic leak complicated by dissection of the interatrial septum after mitral valve replacement. A review of the literature provides confirmation that only 3 cases have been previously reported of this potential, albeit extremely rare, complication of prosthetic mitral valve replacement. Prosthesis oversizing and improper mitral annular handling appeared to be the predisposing factors of this complication.