Italian young doctors' knowledge, attitudes and practices on antibiotic use and resistance: A national cross-sectional survey.

OBJECTIVES: Antimicrobial resistance (AMR) is one of the major health issues worldwide. Clinicians should play a central role to fight AMR, and medical training is a pivotal issue to combat it; therefore, assessing levels of knowledge, attitudes and practices among young doctors is essential for future antimicrobial stewardship (AMS) programmes. METHODS: A nationwide, cross-sectional, multicentre survey was conducted in Italy. A descriptive analysis of knowledge and attitudes was performed, along with a univariate and multivariate analysis of their determinants. RESULTS: Overall, 1179 young doctors accessed the survey and 1055 (89.5%) completed all sections. Regarding the knowledge section of the questionnaire, almost all participants declared to know the different species of bacteria proposed, however the percentage of participants who correctly responded to clinical quizzes was 23% for the question on vancomycin-resistant enterococci (VRE), 42% on carbapenem-resistant Enterobacteriaceae (CRE), 32% on extended-spectrum ß-lactamase-producing enterobacteria (ESBL) and 27% on methicillin-resistantStaphylococcus aureus (MRSA). Similarly, 81% of participants disagreed in stating that AMR was adequately addressed during their medical training and 71% disagreed that they received the right example from their tutors. Finally, a high rate of agreement with the proposed actions to combat AMR was documented; in particular, the percentage agreement was 76% for respondents who agreed to be part of an active surveillance system or AMS programme. CONCLUSIONS: Tackling AMR should be a priority for politicians and for all health workers. Inclusion of competencies in antibiotic use in all specialty curricula is urgently needed.

Maternal caesarean section infection (MACSI) in Sierra Leone: a case-control study.

Sierra Leone is the country with highest maternal mortality and infections are the underlying cause in 11% of maternal deaths, but the real burden remains unknown. This study aims to determine the incidence and risk factors of surgical site infection (SSI) post-caesarean section (CS) in women admitted to Princess Christian Maternity Hospital (PCMH) in Freetown, Sierra Leone. A prospective case-control (1:3 ratio) study was implemented from 1 May 2018 to 30 April 2019 and 11 women presenting with suspected or confirmed infection post-CS were screened for inclusion as a case. For each case, three patients undergoing CS on the same day and admitted to the same ward, but not presenting with SSI, were selected as controls. The post-CS infection rate was 10.9%. Two hundred and fifty-four clinically confirmed cases were enrolled and matched with 762 control patients. By multivariable analysis, the risk factors for SSI were: being single (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.36-1.66), low education level (OR 1.68, 95% CI 1.55-1.84), previous CS (OR 1.27, 95% CI 1.10-1.52), presenting with premature membranes rupture (OR 1.49, 95% CI 1.18-1.88), a long decision-incision time (OR 2.08, 95% CI 1.74-2.24) and a high missing post-CS antibiotic doses rate (OR 2.52, 95% CI 2.10-2.85).

Splenic abscesses as a first manifestation of Crohn's disease: a case report.

BACKGROUND: Splenic nodules are uncommon entities that occur rarely in the general population. Although an infectious etiology (primarily bacteria, followed by mycobacteria) is usually found, noninfectious diseases, including malignancies and autoimmune disorders, can also be involved. For instance, in course of inflammatory bowel diseases (IBDs), in particular Crohn's Disease, aseptic splenic abscesses have been reported in patients with a long history of illness, or in those unresponsive to medical treatments, while are only anecdotally reported in the early phase of the disease. Hence, we presented the case of aseptic splenic nodules as a first manifestation of Crohn's Disease. CASE PRESENTATION: A 21-year-old woman with a silent medical history was admitted to the Emergency Department of our hospital complaining of fever of 38-39 °C (mainly in the evening) for the past 10 days and left flank abdominal pain, accompanied by sweating and fatigue. An abdominal computed tomography showed multiple splenic nodules of unknown origin. Because of the absence of clinical improvement after several antibiotic therapiesand a positron emission tomography (PET) with hypercaptation strictly localized to spleen, she underwent splenectomy, in suspicion of lymphoma. For persistence of symptoms after splenectomy, she underwent many instrumental examination, including a colonoscopy with bowel and intestinal biopsies that poses diagnosis of Crohn's disease. A second PET confirmed this diagnosis showing this time also the gastrointestinal involvement. CONCLUSION: An unusual onset of Crohn's disease with multiple splenic nodules is reported. This case suggests that in light of splenic nodules of unknown etiology attention should be paid to all possible diagnoses of aseptic abscesses, including IBDs (primarily Crohn's Disease).

Validation of the Composite Autonomic Symptom Score 31 (COMPASS 31) for the assessment of symptoms of autonomic neuropathy in people with diabetes.

AIM: To validate the Composite Autonomic Symptom Score (COMPASS) 31, in its Italian version, for the diagnosis of diabetic cardiovascular autonomic neuropathy in a clinic-based, single-centre study. METHODS: A total of 73 participants with diabetes (age 55 ± 14 years) completed the COMPASS 31 questionnaire before undergoing cardiovascular autonomic neuropathy and diabetic polyneuropathy assessment according to cardiovascular reflex tests, neuropathic symptoms and signs, and vibration and thermal thresholds. RESULTS: The COMPASS 31 total weighted score differed between participants with and without cardiovascular autonomic neuropathy (29.9 ± 19.5 vs 16.1 ± 14.7; P = 0.003) and with and without diabetic polyneuropathy (28.9 ± 19.1 vs 12.7 ± 11.3; P < 0.0001). It was related to cardiovascular reflex tests score (rho = 0.38, P = 0.0013) as well as diabetic polyneuropathy symptoms (rho=0.61, P < 0.0001) and signs scores (rho = 0.49, P < 0.0001). Receiver-operating curve analysis showed a fair diagnostic accuracy of total score for cardiovascular autonomic neuropathy (area under the curve 0.748 ± 0.068, 95% CI 0.599-0.861) and diabetic polyneuropathy (area under the curve 0.742 ± 0.061, 95% CI 0.611-0.845). The best score thresholds were 16 for early cardiovascular autonomic neuropathy (sensitivity 75.0%, specificity 64.9%, positive predictive value 37.5% and negative predictive value 90.2%), and 17 for both confirmed cardiovascular autonomic neuropathy and diabetic polyneuropathy (sensitivity 70.0% and 65.5%, respectively; specificity 66.7% and 79.5%, respectively; positive predictive value 25.0% and 67.9%, respectively; and negative predictive value 93.0% and 77.8%, respectively). COMPASS 31 had a good internal consistency according to Cronbach's α coefficient of 0.73. CONCLUSIONS: COMPASS 31 can represent a valid, easy-to-use, quantitative assessment tool for autonomic symptoms in diabetic neuropathy, with a fair diagnostic accuracy for both cardiovascular autonomic neuropathy and diabetic polyneuropathy.

A rare case of necrotic thymoma.

The Authors report the case of a patient who underwent resection of a huge anterior mediastinal mass, revealing to be a necrotic thymoma. The patient had been previously submitted to surgical biopsies of the mass yielding non-diagnostic results due to extensive necrosis. A sternotomy was then performed to resect the mediastinal mass originating from the thymus, en-bloc with the mediastinal fat and the apparently infiltrated lung. Histopathology showed a possible cyst/thymoma in massive necrosis, not further definable; revision by a specialized experienced pathologist (J. Rosai) confirmed total mass necrosis and no lung infiltration, thus orientating diagnosis towards a necrotic thymoma and excluding a lymphoblastic lymphoma, with similar histopathological features but more frequent in children or characterized by neoplastic infiltration of surrounding lung. Total body computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/CT, show neither local recurrence, nor distant metastases two years after surgery. In case of anterior mediastinal mass with difficult histopathological diagnosis due to massive necrosis, the hypothesis of a necrotic thymoma should be considered. After radical removal prognosis is generally favourable and no adjuvant treatment is required.

Understanding the mechanisms of proteinuria: therapeutic implications.

A large body of evidence indicates that proteinuria is a strong predictor of morbidity, a cause of inflammation, oxidative stress and progression of chronic kidney disease, and development of cardiovascular disease. The processes that lead to proteinuria are complex and involve factors such as glomerular hemodynamic, tubular absorption, and diffusion gradients. Alterations in various different molecular pathways and interactions may lead to the identical clinical end points of proteinuria and chronic kidney disease. Glomerular diseases include a wide range of immune and nonimmune insults that may target and thus damage some components of the glomerular filtration barrier. In many of these conditions, the renal visceral epithelial cell (podocyte) responds to injury along defined pathways, which may explain the resultant clinical and histological changes. The recent discovery of the molecular components of the slit diaphragm, specialized structure of podocyte-podocyte interaction, has been a major breakthrough in understanding the crucial role of the epithelial layer of the glomerular barrier and the pathogenesis of proteinuria. This paper provides an overview and update on the structure and function of the glomerular filtration barrier and the pathogenesis of proteinuria, highlighting the role of the podocyte in this setting. In addition, current antiproteinuric therapeutic approaches are briefly commented.

[Overexpression of laminine-5( LN-5) in peritoneal lavage of colorectal cancer patients preliminary results]. / Overexpression della laminina-5 (LN-5) nel lavaggio peritoneale di pazienti con carcinomi del grosso intestino. Risultati preliminari.

Recent studies show that interaction between LN (heterotrimeric protein formed by a3/b3/g2 chains) and cancer cells plays an important role in tumor invasion, also in colorectal cancer. The overall survival was significantly worse in patients with free peritoneal cancer cells(FPTCs): detection of FPTCs after curative surgery is a challenge, because could improve staging and prognosis. Peritoneal citology is the current standard procedure with very low sensivity. We aimed to study the expression of LN5 in the peritoneal lavage of colorectal cancer pts and in controls with semiquantitative reverse trancriptase-polymerase chain reaction (RT-PCR). LN-5 overexpression was evaluated observing PCR- products intensity at electrophoresis: high intensity is correlated to overexpression. Pre and post-operative peritoneal lavages of 30 pts with colorectal cancer (13M;17F), with median age of 69 (58-84), and of 10 controls, were analyzed by conventional cytology and a semiquantitative RT-PCR. No cancer pts showed pre/postoperative negative cytology and did not express LN-5. In cancer pts. cytology was positive in 2 pts in pre/postoperative lavage. LN-5 overexpression was observed in 56,6% preoperatively and in 76,6% postoperatively. LN-5 g 2 chain was most frequent chain. Our study suggests a relationship between LN-5 and FPTCs, as shown by the low expression of lamimine in controls. LN-5 could be a useful marker to identify a subgroup of early-stage patients at increased risk of recurrence; moreover, mortality seems to correlated to LAMB3 chain. The diagnostic accuracy could be improved by using a quantitative RT-PCR or western-blot and detecting serum laminine. Finally, to validate these findings a larger number of pts with follow-up study is required.

Predictive value of technetium-99m sestamibi in patients with multiple myeloma and potential role in the follow-up.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI or setamibi) has recently been proposed for use in the evaluation of multiple myeloma (MM). The aims of this study were to investigate its potential predictive value in patients with MM and its possible role in the follow-up. Thirty patients with MM who had undergone two 99mTc-MIBI scintigraphic studies at least 2 months apart constituted the study group; 22 of them received chemotherapy in the interval between the two scans. The scans were classified as showing pattern N when only physiological uptake was present, pattern D when diffuse bone marrow uptake was observed, pattern F when areas of focal uptake of the tracer were evident, and pattern F + D when both D and F patterns were observed. Comparative 99mTc-MIBI scintigraphy was considered indicative of disease progression when there was a worsening of the pattern (i.e. from N to D, or from N or D to F or to F + D) or an increase in the pattern D semiquantitative score. It was considered indicative of disease improvement when the opposite trend was observed; otherwise, it was considered to document a stable condition. A significant association was observed between the baseline scintigraphic pattern and clinical status at follow-up in the group of patients evaluated after chemotherapy (chi 2 = 16.7, P < 0.05). A negative baseline 99mTc-MIBI scintigram showed a high predictive accuracy (100%) for remission, while the presence of pattern F or F + D was often associated with a less favourable outcome. A multivariate analysis showed that 99mTc-MIBI uptake pattern has an added value in relation to known prognostic variables such as C-reactive protein. 99mTc-MIBI scintigraphy patterns at follow-up were significantly associated with the clinical status evaluated after chemotherapy (chi 2 = 32.6, P < 0.0001). Considering pattern N as indicating remission, pattern D stable condition, and pattern F or F + D progressive disease, a high concordance between scintigraphic findings and clinical status was found in the 22 patients undergoing chemotherapy (91%). Variation in 99mTc-MIBI findings comparing baseline and follow-up evaluations was significantly associated with clinical status both in patients undergoing chemotherapy (chi 2 = 26.5, P < 0.0005) and in those not undergoing chemotherapy (chi 2 = 8.0, P < 0.005). In conclusion, the results of this study suggest a prognostic value of 99mTc-MIBI scintigraphy in patients with MM and a potential role during the follow-up.

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.

Scintimammography with 99mTc-MIBI versus dynamic MRI for non-invasive characterization of breast masses.

Although mammography remains the technique of choice for the early detection of breast cancer, several imaging techniques, including scintimammography and magnetic resonance imaging (MRI), have recently been proposed as adjuncts for this purpose and included in many diagnostic protocols. This study was undertaken to assess the clinical accuracy of scintimammography with technetium-99m methoxyisobutylisonitrile (MIBI) and contrast-enhanced MRI in the detection of primary breast carcinoma in patients with equivocal mammographic findings. Forty-nine patients with a suspicious breast mass detected either by physical examination or by mammography and ultrasound (US) were studied. All patients underwent scintimammography and dynamic contrast-enhanced MRI 1 week apart. The results of the two techniques were compared and correlated to the final diagnoses. Two independent readers reported the scans using a four-point confidence scale. The areas under the receiver operator characteristic (ROC) curves were obtained. Scintimammography showed an accuracy for tumour detection of 84%, with a sensitivity of 80% and a specificity of 88%. MRI showed an accuracy of 86%, with a sensitivity and specificity of 96% and 75%, respectively. Comparison of the two areas under the ROC curves showed no significant differences between MRI, 0.91+/-0.05 (mean+/-SD), and scintimammography, 0.88+/-0.05 (P=0.9). It is concluded that dynamic MRI and scintimammography possess comparable accuracy in the diagnosis of primary breast carcinoma in patients with equivocal mammographic or US findings.

Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients.

BACKGROUND: Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients. METHODS: From 1 October 1991 to 30 September 1993, 202 IBD patients were diagnosed in three centres of two countries (Italy and The Netherlands) by means of a population-based inception cohort study. Of this group of patients, 160 (79%) were interviewed and examined by a rheumatologist and a gastroenterologist in the period June-September 1996. A total of 139/160 patients had an antero-posterior radiograph of the pelvis, and in 140/160 HLA-B27 was determined. RESULTS: 53 (33.1%) of the 160 patients had experienced at least one musculoskeletal manifestation, 29 (18.1%) satisfied the European Spondylarthropathy Study Group (ESSG) criteria for spondylarthropathy and 5 (3.1%) satisfied the modified New York criteria for ankylosing spondylitis. However, 23 (14.4%) patients developed one or more spondylarthropathy-related manifestations without fulfilling any of the classification criteria. In patients satisfying ESSG criteria a significantly higher frequency of women (P = 0.03), of ocular and liver involvement (P = 0.01 and P = 0.03, respectively), and use of immunosuppressive drugs (P = 0.02) was observed. CONCLUSION: Our study shows a high prevalence of musculoskeletal manifestations in an inception cohort of IBD patients. The clinical spectrum is broader than that defined by spondylarthropathy criteria.

Detection of focal myeloma lesions by technetium-99m-sestaMIBI scintigraphy.

BACKGROUND AND OBJECTIVE: The tracer tachnetium-99m-2-methoxy-isobutyl-isonitrile (Tc99m-sestaMIBI) has recently been shown to concentrate in some neoplastic tissues, including myeloma. We investigated the diagnostic capacity and limits of this procedure in tracing focal myeloma lesions, and compared them with those of conventional radiological procedures (Xr). DESIGN AND METHODS: We studied 55 patients suffering from multiple myeloma (MM) or solitary plasmacytoma in different stages and clinical conditions, or from monoclonal gammopathy of undefined significance (MGUS), by whole body scans obtained 10 minutes after injection of 555 MBq of Tc99m-sestaMIBI. Scans were defined as normal (physiological uptake only), diffuse (presence of bone marrow uptake), or focal (localized areas of uptake), and were compared to conventional skeletal Xr. RESULTS: Thirty patients showed no focal areas of Tc99m-sestaMIBI uptake; this group consisted of 5 patients with MGUS, 6 with MM in stage IA and 2 in stage IIA, 11 patients studied after effective chemotherapy and 6 in early relapse. Twenty-five patients showed one or more spots of focal uptake: all of them had active disease (untreated, resistant or relapsing MM). In the setting of tracing focal lesions, Tc99m-sestaMIBI scans were concordant with the radiological examination in 38 patients and discordant in 17. Among the latter, in 4 cases Tc99m-sestaMIBI revealed focal lesions not detected by Xr, and in 13 cases lytic areas detected by Xr did not show Tc99m-sestaMIBI uptake. INTERPRETATION AND CONCLUSIONS: In untreated patients, the number of lesions revealed by Tc99m-sestaMIBI was comparable to that shown by Xr, while in pretreated patients Tc99m-sestaMIBI traced a number of lesions lower than that detected by Xr. The reason for this discrepancy is that Tc99m-sestaMIBI traces only active lesions. Tc99m-sestaMIBI limitations in identifying focal lesions may derive from the dimension of the smallest traceable lesion (about one centimeter), and from the possibility that focal plasma cell localizations in collapsed bone may not be visualized due to inadequate vascularization. Tc99m-sestaMIBI scintigraphy is an interesting tool for diagnosing, staging and following up focal myeloma lesions, in the bone as well as in soft tissues. It is more specific than conventional Xr in identifying sites of active disease.

Tc-99m sestamibi scintigraphy in multiple myeloma.

Tc-99m sestamibi imaging was performed in two patients with multiple myeloma. Focal areas of increased uptake in one patient and diffuse skeletal uptake in the second patient were found. Tc-99m sestamibi appears to identify bone marrow and osteolytic involvement in multiple myeloma.

Different patterns of technetium-99m sestamibi uptake in multiple myeloma.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) has been proposed as a potential tracer in patients with multiple myeloma (MM). The aims of this study were to evaluate the incidence of various patterns of diffuse 99mTc-MIBI uptake in patients with MM, to assess their relationship with clinical status and stage of disease, and to try to clarify the meaning of the diffuse bone marrow uptake of 99mTc-MIBI. Thirty-nine consecutive patients with MM were studied. Twenty-nine of these patients had active disease (13 in stage I, ten in stage II, and six in stage III) and ten were in remission after chemotherapy. Anterior and posterior whole-body scans were obtained 10 min after i.v. injection of 555 MBq of 99mTc-MIBI. The scans were classified as showing: pattern N, when only physiological uptake was present; pattern D, when diffuse bone marrow uptake was observed; pattern F, when areas of focal uptake of the radiotracer were evident; or pattern D+F, when both D and F patterns were observed. Diffuse bone marrow uptake was scored according to extension and intensity. Seven of the 39 patients (18%) showed pattern N, 18 (46%) pattern D, 2 (5%) pattern F, and 12 (31%) pattern D+F. Of the 32 patients with a positive 99mTc-MIBI scan (i.e. showing pattern D, F or D+F), 29 (91%) had active disease. Only three patients in remission showed pattern D, but with a very low bone marrow uptake score. Both extension and intensity of diffuse bone marrow uptake correlated with the amount of the monoclonal component and the percentage of bone marrow plasma cells. The distribution of the 99mTc-MIBI uptake patterns differed among patients in different stages of disease. Using as criteria for advanced stage the presence of either focal uptake (pattern F or D+F) or pattern D with a high score, high (90%) diagnostic accuracy was obtained. In conclusion, the patterns of 99mTc-MIBI uptake in patients with MM are related to both the clinical status and the stage of disease. The presence of focal uptake or of intense diffuse bone marrow uptake suggests that the patient has active and advanced stage disease, while a negative scan in a patient with MM clearly indicates remission.

[Primary biliary cirrhosis with onset in pregnancy: a case report]. / Cirrosi biliare primitiva insorta in gravidanza: descrizione di un caso.

A case of primary biliary cirrhosis occurred during the first quarter of pregnancy in a 29-years-old primipara is described. Possible relationships with a former anti-hepatitis B vaccination and with positive familiarity reduction of IgA are discussed. Follow-up to the patient after two years therapy with colchicine 1 mg a day is also described.