SARS-CoV-2 vaccine-associated subacute thyroiditis: insights from a systematic review.

PURPOSE: To perform a systematic review on published cases of subacute thyroiditis (SAT) secondary to SARS-CoV-2 vaccination, to highlight main features and increase the awareness of this condition. METHODS: Original reports of SAT developed after SARS-CoV-2 vaccination (mRNA, viral vector, or inactivated virus vaccines) were retrieved from a search of electronic databases. Individual patient data on demographics, medical history, type of vaccine, workup and therapies were collected. Wilcoxon rank-sum, Kruskal-Wallis and chi-squared tests were employed for comparisons. RESULTS: 30 articles including 48 reports were retrieved, 3 additional cases evaluated by the Authors were described and included for analysis. Of the 51 patients, 38 (74.5%) were women, median age was 39.5 years (IQR 34-47). Patients developed SAT after a median of 10 days (IQR 4-14) after the vaccine shot. Baseline thyroid exams revealed thyrotoxicosis in 88.2% of patients, decreasing at 31.6% at follow-up. Corticosteroids were used in 56.4% of treated patients. Patients undergoing non-mRNA vaccines were most frequently Asian (p = 0.019) and reported more frequently weight loss (p = 0.021). All patients with a previous diagnosis of thyroid disease belonged to the mRNA vaccine group. CONCLUSION: SARS-CoV-2 vaccine-associated SAT is a novel entity that should be acknowledged by physicians. Previous history of thyroid disease may predispose to develop SAT after mRNA vaccines, but further studies and larger cohorts are needed to verify this suggestion. SARS-CoV-2 vaccine-associated SAT is usually of mild/moderate severity and could be easily treated in most cases, thus it should not raise any concern regarding the need to be vaccinated.

What factors have impact on glucocorticoid replacement in adrenal insufficiency: a real-life study.

PURPOSE: The impact of patient's characteristics on glucocorticoid (GC) replacement therapy in adrenal insufficiency (AI) is poorly evaluated. Aims of this study were to assess the influence of sex and body weight on GC dosing and to describe the choice of GC in AI of different etiologies. METHODS: We retrospectively evaluated hydrocortisone (HC) equivalent total daily dose (HC-TDD) and per-kg-daily dose (HC-KDD) in 203 patients (104 primary AI [pAI], 99 secondary AI [sAI]) followed up for ≥ 12 months. They were treated with HC, modified-release HC (MRHC) or cortisone acetate (CA) and fludrocortisone acetate (FCA) in pAI. RESULTS: At baseline, CA was preferred both in pAI and sAI; at last visit, MRHC was most used in pAI (49%) and CA in sAI (73.7%). Comparing the last visit with baseline, in pAI, HC-TDD and HC-KDD were significantly lower (p = 0.04 and p = 0.006, respectively), while FCA doses increased during follow-up (p = 0.02). The reduction of HC-TDD and HC-KDD was particularly relevant for pAI women (p = 0.04 and p = 0.002, respectively). In sAI patients, no change of HC-KDD and HC-TDD was observed, and we found a correlation between weight and HC-TDD in males (r 0.35, p = 0.02). CONCLUSIONS: Our real-life study demonstrated the influence of etiology of AI on the type of GC used, a weight-based tailoring in sAI, a likely overdosage of GC treatment in pAI women at the start of treatment and the possibility to successfully increase FCA avoiding GC over-treatment. These observations could inform the usual clinical practice.

The Clean Care Contest: promoting hand hygiene among healthcare and medical students.

INTRODUCTION: Despite continuing efforts, compliance rates and knowledge of best practices in hand hygiene remain disappointing. Recognizing that conventional educational tools seem out of touch with young people and that the med and messages contents need refreshing, the Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health devised a novel approach to promote the creation of innovative educational tools for improving knowledge of, and compliance with, hand hygiene rules among healthcare and medical students. METHODS: A contest in creating educational material on hand hygiene practices involved university students of nursing and medicine, and of other healthcare degrees. Students from the universities of the GISIO network were invited to create educational material (e.g., videos, posters, presentations, leaflets, and screensavers) to be presented by May 5th 2019 during the World Hand Hygiene Day / Save Lives: Clean Your Hands Global Annual Initiative of the World Health Organization). A local and a national winners were awarded. RESULTS: Three different local and national contests were performed during 2016, 2017 and 2018. During the three-year period, more than 270 educational tools have been developed: 130 (48%) were judged useful for hand hygiene promotion campaigns. The most frequent projects participating in the contests were videos (39%), posters (29%), leaflets (14%), and others (18%) submitted by more than 1,500 students of nursing (40%), medicine (31%), dentistry (7%), and of other healthcare courses in 14 universities. Products were evaluated by a local committee and, subsequently, local winners represented their University in a national contest. CONCLUSIONS: The contest provided a framework for the creation of innovative and potentially effective educational tools via an engaging approach that leveraged student creativity. Given the need to improve compliance rates, this study suggests that new ways can be advantageously explored to teach hand hygiene procedures and increase awareness of the importance of their consistent use among healthcare and medical students.

Inflammatory markers predict insulin sensitivity in active rheumatoid arthritis but not in psoriatic arthritis.

Whether the insulin resistance commonly observed in patients with inflammatory arthritis is a disease-specific feature and/or is limited to a disease phase (i.e., it occurs only during phases of high disease activity) is unknown. Fifty-three rheumatoid arthritis (RA) and 44 psoriatic arthritis (PsA) patients were recruited consecutively along with 194 controls matched for age, sex and body mass index for a case-control study. All underwent an oral glucose tolerance test, the results of which were analysed to derive the following indexes: homeostatic model of insulin resistance (HOMA-IR), insulin sensitivity index (ISI) and early insulin sensitivity index (EISI). These data were related to anthropometric, clinical and laboratory findings. Metabolic parameters of patients and controls were similar. Neither inflammatory markers nor disease activity scores were related to glucose metabolism for the generality of RA and PsA patients; however, by restricting the analysis to the subset of RA patients with residual disease activity, an association emerged between erythrocyte sedimentation rate, on the one hand, and fasting insulin (ß=0.46, p=0.047) and HOMA-IR (ß=0.44, p=0.02), on the other. Moreover, C-reactive protein (CRP) levels were associated with plasma glucose and insulin levels measured 120 min after the glucose load (ß=0.91, p=0.0003 and ß=0.77, p=0.0006, respectively); ISI and EISI were predicted by CRP (ß=-0.79, p=0.0006; ß=-0.80, p=0.0001, respectively). The same did not hold true for PsA patients. The association between systemic inflammation and insulin resistance indexes is a feature of RA with residual disease activity, not a universal feature of inflammatory arthritides.

Essential strategies in HAI prevention and control: performance assessment through the implementation of the HAI-CoSIP tool of the GISIO-SItI group. A pilot study in a sample of Italian Organizations.

BACKGROUND: Healthcare-Associated Infections are a great concern for worldwide healthcare systems and represent a considerable threat to patient safety, leading to adverse clinical outcomes. A defined panel of indicators represents a key element to guide Healthcare Organizations towards identification of main gaps, implementation of effective actions and continuous improvements on Healthcare-Associated Infections prevention and control activities. A review on accreditation systems conducted by the Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene Preventive Medicine and Public Health revealed a substantial heterogeneity of implemented standards and led to the development of a core set of indicators and requirements for Healthcare-Associated Infections' prevention and control within the hospital setting. The main aim of the study was to test the feasibility of the Healthcare-Associated Infections' prevention and control within the hospital setting tool to calculate performance scores on a sample of Italian Healthcare Organizations and to identify major critical issues. The potential benefits of the possibility of future implementation of the tool within Institutional Accreditation Programs is discussed. STUDY DESIGN: Cross sectional pilot survey. METHODS: The Healthcare-Associated Infections' prevention and control within the hospital setting included 96 criteria and 20 key areas including an area for outcomes indicators. For applicable criteria, standards fulfilment was evaluated according to a 4 point Likert scale. A composite score was calculated for each Healthcare Organization and five performance levels were identified. Data were further analysed by computing performance scores at the level of each area and requirement. RESULTS: 20 Healthcare Organizations agreed to take part in this pilot study including two rehabilitative Healthcare Organizations. Among the whole sample a mean of 12.20% of requirements resulted not fulfilled, leaving space for further improvements. Critical areas were easily identified and the instrument was able to capture substantial differences between Healthcare Organizations. Only a few number of standards resulted "Not Applicable" (Mean = 4.71%) and most of them regarded Rehabilitative Healthcare Organizations. Mean composite performance index resulted 74.06% (SD = 16.96, range 36.30 - 94.27%); area of outcome indicators obtained a mean score of 56.17. CONCLUSION: The Healthcare-Associated Infections' prevention and control within the hospital setting resulted an useful tool to assess Healthcare Organizations' performance in the field of Healthcare-Associated Infections prevention and control and to identify necessary actions for further improvements. The distribution of total scores by Healthcare Organizations showed a high heterogeneity. Implementation of the Healthcare-Associated Infections' prevention and control within the hospital setting tool as an institutional accreditation tool may help to drive the required harmonization at a national level of Healthcare-Associated Infections management and control strategies and overcome current substantial regional differences.

Procedures in endoscope reprocessing and monitoring: an Italian survey.

BACKGROUND: The high diffusion of endoscopes worldwide and the need for effective reprocessing methods requested the development of guidelines and implementation of surveillance procedures at local level. STUDY DESIGN: In order to collect data on everyday's practice and adherence to available guidelines, endoscopy units from different public institutions were surveyed using a dedicated questionnaire. METHODS: Between July and November 2015 a survey was carried in 12 main hospitals from 10 different Italian regions, involving 22 endoscopy units. The state of the art of national and international guidelines was investigated to compare the protocols adopted at local level. RESULTS: In all the surveyed hospitals, the reprocessing activity is based on pre-established protocols in adherence with principal guidelines. Enzymatic detergents, which are recommended by the international guidelines, are used in 55.6% of units and peracetic acid is currently the most widely used chemical disinfectant. Discrepancies were observed in the application of periodic quality controls. CONCLUSION: Updated guidelines are generally applied in reprocessing practice. Quality controls may represent a critical issue to improve effectiveness and surveillance. The whole of acquired data can promote a positive trend towards the application of best practices.

A multicentre study on epidemiology and prevention of needle stick injuries among students of nursing schools.

INTRODUCTION: Among the health professions with a long period of training, the students of the Nursing Bachelor's Degree are the most exposed to biological risk resulting from accidents, in particular with needles and cutting edges. The aim of the study was to estimate the frequency and the circumstances for the occurrence of needle stick injuries, as a knowledge base for targeted prevention interventions. METHODS: The study was carried out between May and July 2017 in 11 Universities in Italy and 1 in Albania (associated with the "Tor Vergata" University of Rome). An anonymous semi-structured questionnaire was proposed to 1st (second semester), 2nd and 3rd year students of Nursing Bachelor's Degree. RESULTS: A total of 2742 questionnaires were collected. The average age of participants was 22.9 years (median 22, range 19-60 years), 73% of whom were females. A total of 381 injuries were reported. Three hundred and sixteen students (11.8%) underwent at least 1 injury (12.7% among females, 9.7% among males); 41 students declared two or more injuries; four students did not report the number of injuries occurred. The first injury occurred, as an average, 17 days after the start of the internship (median 15 days) and, in 25% of the cases, during the first 9 days. The highest percentage of accidents occurred during the first internship (25.3% of the total) and decreased with the progress of the training path. The injuries occurred in 38% of cases during drug preparation, 24% when disposing of sharp devices, 15% while re-capping needles, 13% during blood sampling and 10% in other circumstances. In 51.2% of cases, the needle was not sterile. Among the nursing students who suffered a needle stick injury, 58.1% declared that they had performed the post-exposure prophylaxis. 96% of students stated to be vaccinated against Hepatitis B virus. Amongst the students who had their serological status checked (74%), 18% stated the antibody titre was not protective. 49.8% of students answered to have been trained in advance on the correct procedures to avoid needle stick and cutting edges injuries in each clinical ward attended, 41.2% referred that this occurred only in some wards and 10% in no ward at all. CONCLUSION: The results of this study show a high percentage of needle stick injuries in students of the Nursing Bachelor's Degree. Therefore, there is a need for careful reflection on the most effective methods of targeted training acquisition of knowledge, skills and behavioural models useful for the exercise of the profession.

Hospital hygiene in Italy: the GISIO-SItI survey.

BACKGROUND: In Italy there are no rules concerning the establishment of a hospital hygiene structure in hospitals and other healthcare settings, and the hospital organization plans vary widely. The aim of the survey, carried out by the Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive medicine and Public health, was to evaluate the presence in the hospital organization plan of a structure referred to as Hospital hygiene, or including in its denomination the words "hygiene" or "hospital hygiene", the activities carried out, the relation to other areas, like patient safety, the type and quantity of professionals involved, the strengths and the critical aspects. METHODS: A semi-structured questionnaire was administered to Healthcare Trusts representing all Italian Regions through the members of the above Study Group. RESULTS: 35 Trusts, 13 in Northern, 8 in Central, 14 in Southern Italy (including Sicily and Sardinia), completed the questionnaire. In 19 Trusts (54.3%) a structure whose denomination included the words "hospital hygiene" or "hygiene" was present. The activities related to the management of infectious risk were most represented, carried out autonomously or in collaboration, but many other activities were covered. In all hospitals the activities of the Hospital Hygiene Unit inter-linked with those of the clinical risk, with different forms of collaboration. CONCLUSION: This survey, even though on a limited sample, provided a picture of hospital hygiene at a national level, showing a considerable heterogeneity and highlighting critical issues but also strengths. It is essential to share organizational and management models that enhance and promote hospital hygiene, to ensure the appropriateness of healthcare practices offered in a safe and comfortable environment to patients, operators, and visitors.

Knowledge, experiences, and attitudes toward Mantoux test among medical and health professional students in Italy: a cross-sectional study.

BACKGROUND: The World Health Organization's Action Framework for tuberculosis elimination in low-tuberculosis incidence countries includes the screening for active and latent tuberculosis in selected high-risk groups, including health care workers. In this context, medical and health profession students, exposed to nosocomial tuberculosis transmission during training and clinical rotations, are target populations for tuberculosis screening. No updated data are available on tuberculosis screening practice and knowledge of medical and health profession students in Italy. METHODS: Within the activities Italian Study Group on Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health, we carried out a multicentre cross-sectional study to assess knowledge, attitude and practices on tuberculosis prevention and control among Medical, Dentistry, Nursing and other health professions' students. Students were enrolled in the study on a voluntary basis and were administered a previously piloted structured questionnaire. Logistic regression models were applied to explore knowledge on tuberculosis prevention by selected socio-demographic variables and University-based tuberculosis prevention practice. RESULTS: Students of seventeen Universities across Italy participated in the study, and 58.2% of them received compulsory tuberculin skin test either at enrollment or while attending clinical practice. A total of 5,209 students filled the questionnaire. 37.7% were medicine and dentistry students (Group 1), 44.9% were nursing students (Group 2) and 17.4% were other health professions' students (Group 3). Age and gender had different distributions by groups, as well as knowledge and practice on tuberculin skin test. 84.4% of the study population (95% CI = 83.3-85.3) was aware of the existence of the tuberculin skin test, 74.4% (95% CI = 73.2-75.6) knew what is the first-level screening test for latent tuberculosis and only 22.5% (95% CI = 21.4-23.6) knew how to proceed after a positive tuberculin skin test result. Overall, knowledge on tuberculosis prevention was higher in Group 2 and lower Group 3, as compared to Group 1. CONCLUSION: In Italy, the knowledge on tuberculosis screening among University students is generally good. To reduce some of the criticalities found among the different study courses, it would be appropriate to harmonize both the regulations on tuberculosis screening practices for admission to University courses, and the educational activities on the topic of tuberculosis, to be extended to all workers involved in health care setting.

Cell wall changes during the formation of aerenchyma in sugarcane roots.

Background and Aims: Aerenchyma develops in different plant organs and leads to the formation of intercellular spaces that can be used by the plant to transport volatile substances. Little is known about the role of cell walls in this process, although the mechanism of aerenchyma formation is known to involve programmed cell death and some cell wall modifications. We assessed the role that cell wall-related mechanisms might play in the formation of aerenchyma in sugarcane roots. Methods: Sections of roots (5 cm) were subjected to microtomography analysis. These roots were divided into 1-cm segments and subjected to cell wall fractionation. We performed analyses of monosaccharides, oligosaccharides and lignin and glycome profiling. Sections were visualized by immunofluorescence and immunogold labelling using selected monoclonal antibodies against polysaccharide epitopes according to the glycome profiles. Key Results: During aerenchyma formation, gas spaces occupied up to 40 % of the cortex cross-section within the first 5 cm of the root. As some of the cortex cells underwent dissolution of the middle lamellae, leading to cell separation, cell expansion took place along with cell death. Mixed-linkage ß-glucan was degraded along with some homogalacturonan and galactan, culminating in the formation of cell wall composites made of xyloglucan, arabinoxylans, cellulose and possibly lignin. Conclusion: The composites formed seem to play a role in the physical-chemical properties of the gas chambers, providing mechanical resistance to forces acting upon the root and at the same time decreasing permeability to gases.

Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.

Definition of criteria and indicators for the prevention of Healthcare-Associated Infections (HAIs) in hospitals for the purposes of Italian institutional accreditation and performance monitoring.

BACKGROUND: Healthcare-associated infections (HAIs) are an important issue in terms of quality of care. HAIs impact patient safety by contributing to higher rates of preventable mortality and prolonged hospitalizations. In Italy, analysis of the currently available accreditation systems shows a substantial heterogeneity of approaches for the prevention and surveillance of HAIs in hospitals. The aim of the present study is to develop and propose the use of a synthetic assessment tool that could be implemented homogenously throughout the nation. METHODS: An analysis of nine international and of the 21 Italian regional accreditation systems was conducted in order to identify requirements and indicators implemented for HAI prevention and control. Two relevant reviews on this topic were further analyzed to identify additional evidence-based criteria. The project team evaluated all the requirements and indicators with consensus meeting methodology, then those applicable to the Italian context were grouped into a set of "focus areas". RESULTS: The analysis of international systems and Italian regional accreditation manuals led to the identification respectively of 19 and 14 main requirements, with relevant heterogeneity in their application. Additional evidence-based criteria were included from the reviews analysis. From the consensus among the project team members all the standards were compared and 20 different thematic areas were identified, with a total of 96 requirements and indicators for preventing and monitoring HAIs. CONCLUSIONS: The study reveals a great heterogeneity in the definition of accreditation criteria between the Italian regions. The introduction of a uniform, synthetic assessment instrument, based on the review of national and international standards, may serve as a self-assessment tool to evaluate the achievement of a minimum standards set for HAIs prevention and control in healthcare facilities. This may be used as an assessment tool by the Italian institutional accreditation system, also useful to reduce regional disparities.

Cross-sectional study on knowledge of health care workers about Ebola Virus Disease and its prevention: a pilot study in two hospitals in Rome (Italy).

OBJECTIVES: To carry out a pilot study aimed: a) to define and validate a method to evaluate Health Care Workers' (HCWs') knowledge about Ebola virus disease (EVD); b) to verify if the specific training on EVD followed in Emergency Units is associated to a significant difference in knowledge. METHODS: A cross-sectional study was carried out using an "ad hoc" questionnaire. It included 20 statements true/false, divided into three areas: risk of transmission (T); prevention and personal protection (PPP); environmental prevention (EP). The targets were the HCWs of Emergency Unit (trained) and Internal Medicine Units (control) of two hospitals in Rome (A and B). Internal consistency was evaluated using KR-20 coefficient. A proportion of 14/20 (70%) correct answers was considered acceptable. Mean scores and acceptable scores were compared using t-Student test and chi-squared test respectively. A logistic regression was fitted to identify independent factors associated with acceptable knowledge level for the whole questionnaire and each area. RESULTS: 237 HCWs were included in the pilot study, with a participation percentage of 89.1%. The reliability coefficient (KR-20) was 0.6 for the entire 20-item questionnaire. Overall proportion of respondents with acceptable score was 32.9%; the highest proportion (61.1%) was found in trained HCWs (p<0.02). Factors associated with an acceptable knowledge were: belonging to hospital A (p<0.001) and having been trained on EVD (p=0.03). Stratifying by area, the variables significantly related to an acceptable score were: for PPP area younger HCWs (p<0.01) and nurses (p<0.01); for EP area, belonging to hospital A (p<0.01) and to Internal Medicine Unit (p=0.02). CONCLUSIONS: The high compliance and completeness of the responses indicate the validity of the method of administration adopted. In the investigated hospitals the specific training on EVD determined a significant overall improvement in knowledge. It will be appropriate to extend the study to other hospitals around the Country to evaluate the true effectiveness of the training in a larger sample of hospitals.

Striatin knock out induces a gain of function of INa and impaired Ca2+ handling in mESC-derived cardiomyocytes.

AIM: Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated. METHODS: We studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn-KO and isogenic WT mouse embryonic stem cell lines. RESULTS: The spontaneous beating rate of Strn-KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2-8 Hz) Strn-KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn-KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn-KO CMs than in WT. Indeed, incubation of Strn-KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels. CONCLUSION: Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn-related multi-protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement.

Comparative population analysis of Klebsiella pneumoniae strains with extended-spectrum ß-lactamases colonizing patients in rehabilitation centers in four countries.

The international project MOSAR was conducted in five rehabilitation centers; patients were screened for rectal carriage of extended-spectrum ß-lactamase (ESBL)-producing members of the Enterobacteriaceae. Among 229 Klebsiella pneumoniae isolates, four clonal groups (CG) or complexes (CC) prevailed: CG17 in France, CG101 in Italy, CG15 in Spain, and CC147 in Israel. ESBLs, mainly CTX-Ms, were produced by 226 isolates; three isolates expressed AmpC-like cephalosporinases. High genetic diversity of K. pneumoniae populations was observed, with specific characteristics at each center.

Clonal structure, extended-spectrum ß-lactamases, and acquired AmpC-type cephalosporinases of Escherichia coli populations colonizing patients in rehabilitation centers in four countries.

The prospective project MOSAR was conducted in five rehabilitation units: the Berck Maritime Hôpital (Berck, France), Fondazione Santa Lucia (Rome, Italy), Guttmann Institute (GI; Barcelona, Spain), and Loewenstein Hospital and Tel-Aviv Souraski Medical Center (TA) (Tel-Aviv, Israel). Patients were screened for carriage of Enterobacteriaceae resistant to expanded-spectrum cephalosporins (ESCs) from admission until discharge. The aim of this study was to characterize the clonal structure, extended-spectrum ß-lactamases (ESBLs), and acquired AmpC-like cephalosporinases in the Escherichia coli populations collected. A total of 376 isolates were randomly selected. The overall number of sequence types (STs) was 76, including 7 STs that grouped at least 10 isolates from at least three centers each, namely, STs 10, 38, 69, 131, 405, 410, and 648. These clones comprised 65.2% of all isolates, and ST131 alone comprised 41.2%. Of 54 STs observed only in one center, some STs played a locally significant role, like ST156 and ST393 in GI or ST372 and ST398 in TA. Among 16 new STs, five arose from evolution within the ST10 and ST131 clonal complexes. ESBLs and AmpCs accounted for 94.7% and 5.6% of the ESC-hydrolyzing ß-lactamases, respectively, being dominated by the CTX-M-like enzymes (79.9%), followed by the SHV (13.5%) and CMY-2 (5.3%) types. CTX-M-15 was the most prevalent ß-lactamase overall (40.6%); other ubiquitous enzymes were CTX-M-14 and CMY-2. Almost none of the common clones correlated strictly with one ß-lactamase; although 58.7% of ST131 isolates produced CTX-M-15, the clone also expressed nine other enzymes. A number of clone variants with specific pulsed-field gel electrophoresis and ESBL types were spread in some locales, potentially representing newly emerging E. coli epidemic strains.

Preaponeurotic endoscopic repair (REPA) indication in men could be controversial.

PURPOSE: To evaluate the outcomes of REPA and establish if any differences in complications and evolution are present between males and females. METHODS: A retrospective study including consecutive patients operated by REPA approach between November 2017 and April 2019 was conducted. Demographic data, operative times, postoperative complications, and hospital stay were analyzed. The EuraHS-QoL score was used to assess postoperative pain, daily activity constraints, and aesthetic discomfort. The results were compared between sexes. Statistical analysis was performed using SPSS 19. RESULTS: Fifty-four patients were included and 53.7% were male. Patients had a mean age of 50.7 years and a mean BMI of 28.7. The average RAD (Rectus Abdominis Diastasis) size was 2.6 cm (range of 2-5 cm). Seroma was significantly more frequent in males, with an incidence of 55.2 and 24% for females (p = 0.02). Three cases required reintervention (5.5% of total cases), which corresponded to a cystic seroma, an abdominal wall hematoma, and a hernia recurrence. The three cases were males and a p value of 0.04 was obtained when comparing reintervention rates between males and females. No cases of surgical wound infection nor cutaneous necrosis were recorded. No conversions were needed. The mean postoperative pain was 2.25, the mean daily activity constraints score was 2.63, and the degree of aesthetic discomfort was 1.23 with no significant differences between groups. CONCLUSION: The correction of small midline defect associated with minor RAD using REPA seems feasible and reproducible. REPA had achieved good results in females, but in males, the outcomes were poorer.

Depletion of RT6.1+ T lymphocytes induces diabetes in resistant biobreeding/Worcester (BB/W) rats.

To investigate the role of RT6+ T cells in the pathogenesis of diabetes in BB/W rats, we treated animals from the diabetes-resistant (DR) subline with anti-RT6.1 lymphocytotoxic mAb. This depleted greater than 95% of peripheral RT6+ T cells but did not substantially reduce levels of circulating T cells or the in vitro response of spleen cells to mitogen. Treatment of 30-d-old DR BB/W rats in this way: induced insulitis and diabetes, rendered nondiabetic RT6-depleted DR rats susceptible to the adoptive transfer of diabetes by spleen cells from acutely diabetic BB/W rats, and yielded DR spleen cell populations capable of the adoptive transfer of diabetes to diabetes-prone (DP) or DR recipients. Treatment of DR rats beginning at 60 d of age failed to produce these effects. These results suggest that both susceptibility and resistance to diabetes in the BB/W rat are in part regulated by the RT6+ T cell subset and provide evidence for the importance of regulatory T lymphocytes in the pathogenesis of autoimmunity and diabetes in BB/W rats.

Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes.

Essential fatty acid (EFA) deficiency exerts a striking protective effect in several animal models of autoimmune disease. We now report that EFA deprivation prevents diabetes in the BB rat, an animal model of human insulin-dependent diabetes mellitus. In diabetes-prone (DP)-BB rats, the incidences of spontaneous diabetes and insulitis (the pathological substrate of autoimmune diabetes) were greatly reduced by EFA deficiency. This beneficial effect of the deficiency state was also seen in diabetes-resistant (DR)-BB rats that, after treatment with antibody to eliminate RT6+ T cells, would otherwise have become diabetic. The susceptibility of EFA-deprived DP-BB rats to spontaneous diabetes was restored when they were given dietary supplements of linoleate at 70 d of age (during the usual period of susceptibility), but not when they were repleted beginning at 120 d (after the peak incidence of diabetes). EFA deficiency did lead to growth retardation, but calorically restricted control rats demonstrated that the protective effect of the deficiency state was not a function of decreased weight. To examine the relationship between the biochemical changes of EFA deficiency and its physiological effects in this system, we compared the fatty acid changes that occurred in EFA-deficient animals that did and did not develop diabetes. Nondiabetic animals had significantly lower levels of (n-6) fatty acids (i.e., linoleate and arachidonate) and higher levels of oleate, an (n-9) fatty acid, than did diabetic animals. Levels of 20:3(n-9), the fatty acid that uniquely characterizes EFA deficiency, were similar in both groups, however. Among diabetic EFA-deficient rats, the age at onset of diabetes was found to correlate inversely with the level of (n-6) fatty acids, the least depleted animals becoming diabetic earliest, whereas there was no correlation with levels of 20:3(n-9). Among animals repleted with linoleate beginning at 70 d, restoration of susceptibility to diabetes correlated with normalization of the level of arachidonate. In summary, EFA deprivation reduced the frequency of diabetes in both DP and RT6-depleted DR-BB rats. This protective effect was strongly associated with depletion of (n-6) fatty acids, particularly arachidonate, but not with accumulation of the abnormal 20:3(n-9). Conjecturally, arachidonate and/or a metabolite may play a key role in mediating inflammatory injury in this animal model of autoimmune diabetes.

Allografts stimulate cross-reactive virus-specific memory CD8 T cells with private specificity.

Viral infections have been associated with the rejection of transplanted allografts in humans and mice, and the induction of tolerance to allogeneic tissues in mice is abrogated by an ongoing viral infection and inhibited in virus-immune mice. One proposed mechanism for this 'heterologous immunity' is the induction of alloreactive T cell responses that cross-react with virus-derived antigens. These cross-reactive CD8 T cells are generated during acute viral infection and survive into memory, but their ability to partake in the immune response to allografts in vivo is not known. We show here that cross-reactive, virus-specific memory CD8 T cells from mice infected with LCMV proliferated in response to allografts. CD8 T cells specific to several LCMV epitopes proliferated in response to alloantigens, with the magnitude and hierarchy of epitope-specific responses varying with the private specificities of the host memory T cell repertoire, as shown by adoptive transfer studies. Last, we show that purified LCMV-specific CD8 T cells rejected skin allografts in SCID mice. These findings therefore implicate a potential role for heterologous immunity in virus-induced allograft rejection.