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Mosaic variegated aneuploidy (MVA) is an autosomal recessive disorder characterized by mosaic aneuploidies, predominantly trisomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies, and most patients present with intrauterine growth delay, microcephaly, and a broad spectrum of congenital abnormalities. We report a patient with a distinctive type of MVA discovered in bone marrow (BM) when she was 3-month-old due to neutropenia and hypocellular bone marrow. She was followed up for more than 20 years, and different trisomic cells were repeatedly discovered in different tissues, whereas her clinical picture has never been severe. The main sign remained intermittent neutropenia, not cyclic and often not too severe, occasionally with anemia and thrombocytopenia. Retromicrognathia was the only dysmorphic sign. Unlike other patients with MVA, the trisomies in all tissues involved almost invariably chromosomes 18 and 19. Therefore, the peculiarities of our patient were the clinical and the atypical cytogenetic pictures. Nevertheless, we looked for mutations in the seven causative genes of the known types of MVA, but the results were negative. Then, we analyzed the entire exome to find out other possible causing mutations, but also this attempt failed to discover a possible cause of this distinctive form of MVA., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Objectives: To determine if circulating mitochondrial deoxyribonucleic acid levels increase after sport activity involving blows to the head, such as boxing, and if it could play a role in inflammatory cascade regulation in response to trauma., Design: Observational, longitudinal., Methods: We measured mitochondrial deoxyribonucleic acid levels and integrity in ten non-professional male boxers before and after three weekly sparring matches. We set up a protocol to separate three different plasma fractions enriched in mitochondria-containing vesicles, mitochondrial deoxyribonucleic acid bound to proteins and naked mitochondrial deoxyribonucleic acid. We quantified the levels of the main cytokines involved in inflammatory response and the levels of neurofilament light, a well-known marker of brain damage., Results: Circulating mitochondrial deoxyribonucleic acid levels increased after each match. In the second fraction, we also observed an increase over the weeks. Mitochondrial deoxyribonucleic acid is less intact after each match if compared with pre-match integrity, especially the naked form which is not protected within vesicles or mitochondria. Circulating levels of interleukin-6, interleukin-1beta and interleukin-10 increased after each match linking traumatic brain injuries to inflammatory state. Neurofilament light chain showed a similar trend to mitochondrial deoxyribonucleic acid., Conclusions: As mitochondrial deoxyribonucleic acid displays an inflammatory effect and neurofilament light chain is more specific for brain injury, we concluded that the simultaneous analysis of these two parameters could be helpful to monitor the effects of traumatic brain injury in contact sports, and that mitochondrial deoxyribonucleic acid is a promising candidate biomarker to study the inflammatory state of patients who suffered repeated traumatic brain injuries., Competing Interests: Declaration of interest statement The authors declare that there are no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the "toolbox" to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets.

The patient reported here underwent hematopoietic stem cell transplantation (HSCT) due to chronic granulomatous disease (CGD) caused by biallelic mutations of the NCF1 gene. Two years later, he developed AML, which was unexpected and was recognized via sex-mismatched chromosomes as deriving from the donor cells; the patient was male, and the donor was his sister. Donor cell leukemia (DCL) is very rare, and it had never been reported in patients with CGD after HSCT. In the subsequent ten years, the AML relapsed three times and the patient underwent chemotherapy and three further HSCTs; donors were the same sister from the first HSCT, an unrelated donor, and his mother. The patient died during the third relapse. The DCL was characterized since onset by an acquired translocation between chromosomes 9 and 11, with a molecular rearrangement between the MLL and MLLT3 genes-a quite frequent cause of AML. In all of the relapses, the malignant clone had XX sex chromosomes and this rearrangement, thus indicating that it was always the original clone derived from the transplanted sister's cells. It exhibited the ability to remain quiescent in the BM during repeated chemotherapy courses, remission periods and HSCT. The leukemic clone then acquired different additional anomalies during the ten years of follow-up, with cytogenetic results characterized both by anomalies frequent in AML and by different, non-recurrent changes. This type of cytogenetic course is uncommon in AML.

Background: Obstetric brachial plexus injury (OBPI) is a weakening or paralysis of the upper arm caused by brachial plexus injury followed by a muscle paralysis with severe repercussions on the movement of the shoulder joint following a progressive glenohumeral joint deformity. This case series analyzes the clinical and radiological outcomes of reverse total shoulder arthroplasty (RSA) in OBPI patients with a follow-up of 2 years., Materials and Methods: OBPI patients with secondary end-stage glenohumeral arthritis were enrolled in the study and they were treated with RSA. Patient demographics and clinical outcomes [Range of Motion (ROM), Visual Analog Scale (VAS), Oxford Shoulder Score (OSS)] were evaluated. A novel Shoulder motion analysis was carried out to investigate specific movement patterns of scapulothoracic movements in these patients. This study is a prospective cohort study., Results: Four Patients (M: F = 1:3) were enrolled in the study, the mean age was 49.3 years (+ 2.75), the mean OSS (Oxford Shoulder Score) decreased from 48.8 (± 2.5) preoperatively to 18.30 (± 2.78), the mean VAS (Visual Analog Scale) decreased from 7.25 (± 0.5) to 1.7 (± 0.3) in the follow up (∆% relative pain reduction:- 76.5%), Shoulder ROM obtained an improvement (p < 0.05) except for abduction and external rotation. The average follow-up time was 26.3 months (+- 4.5). Shoulder motion analysis showed a complete loss of the scapular tilting above 90 degrees of flexion compared to the typical one of standard RSA with a pattern shifted towards scapular retraction (engaging trapezius and rhomboid muscles) to compensate the loss of the posterior tilting., Conclusions: RSA in OBPI patients demonstrated a significant improvement of pain symptoms and a moderate improvement in daily activities, anyway with a more appreciable quality of life over time even if the marked hypotrophy especially of the posterior shoulder muscles showed some limits in maintaining suspension of the upper limb and a minor external rotation, with an internal rotation attitude during the movements., Level of Evidence: Level IV, Case series., (© 2023. The Author(s).)

Introduction: One of the main causes of RSA failure is attributable to the malpositioning of the glenoid component. Initial experiences with computer-assisted surgery have shown promising results in increasing the accuracy and repeatability of placement of the glenoid component and screws. The aim of this study was to evaluate the functional clinical results, in terms of joint mobility and pain, by correlating them with intraoperative data regarding the positioning of the glenoid component. The hypothesis was that the lateralization more than 25 mm of the glenosphere can led to better stability of the prosthesis but should pay in term of a reduced range of movement and increased pain., Materials and Methods: 50 patients were enrolled between October 2018 and May 2022; they underwent RSA implantation assisted by GPS navigation system. Active ROM, ASES score and VAS pain scale were recorded before surgery. Preoperative data about glenoid inclination and version were collected by pre-op X-Rays an CT. Intraoperative data-inclination, version, medialization and lateralization of the glenoid component-were recorded using computer-assisted surgery. 46 patients had been further clinically and radiographically re-evaluated at 3-months, 6-months, 1-year, and 2-years follow-up., Results: We found a statistically significant correlation between anteposition and glenosphere lateralization value (DM - 6.057 mm; p = 0.043). Furthermore a statistically significant correlation has been shown between abduction movement and the lateralization value (DM - 7.723 mm; p = 0.015). No other statistically significant associations were found when comparing the values of glenoid inclination and version with the range of motion achieved by the patients after reverse shoulder arthroplasty., Conclusion: We observed that the patients with the best anteposition and abduction results had a glenosphere lateralization between 18 and 22 mm. When increasing the lateralization above 22 mm or reducing it below 18 mm, on the other hand, both movements considered decreased their range., Level of Evidence: Level IV; Case Series; Treatment Study., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic myeloid leukemia (CML) is a rare myeloproliferative disorder caused by the reciprocal translocation t(9;22)(q34;q11) in hematopoietic stem cells (HSCs). This chromosomal translocation results in the formation of an extra-short chromosome 22, called a Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene responsible for the expression of a constitutively active tyrosine kinase that causes uncontrolled growth and replication of leukemic cells. Mechanisms behind the formation of this chromosomal rearrangement are not well known, even if, as observed in tumors, repetitive DNA may be involved as core elements in chromosomal rearrangements. We have participated in the explorative investigations of the PhilosoPhi34 study to evaluate residual Ph+ cells in patients with negative FISH analysis on CD34+/lin- cells with gDNA qPCR. Using targeted next-generation deep sequencing strategies, we analyzed the genomic region around the t(9;22) translocations of 82 CML patients and one CML cell line and assessed the relevance of interspersed repeat elements at breakpoints (BP). We found a statistically higher presence of LINE elements, in particular belonging to the subfamily L1M, in BP cluster regions of both chromosome 22 and 9 compared to the whole human genome. These data suggest that L1M elements could be potential drivers of t(9;22) translocation leading to the generation of the BCR-ABL1 chimeric gene and the expression of the active BCR-ABL1 -controlled tyrosine kinase chimeric protein responsible for CML.

Sharp injuries, determining the risk of bloodborne infections and psychological distress in healthcare workers, may be prevented by a set of strategies, legally enforced in Europe through the Directive 2010/32/EU. To assess its level of implementation in Italy, a national survey was conducted in 2017 and again in 2021, evaluating the progress and possible drawbacks of the COVID-19 pandemic. Altogether, 285 safety managers and 330 nurses from a representative sample of 97 and 117 public hospitals were interviewed using a standardized questionnaire. Knowledge of the Directive requirements decreased significantly, with <60% of participants answering correctly in 2021, and nurses' attendance in specific courses dropped to 25% in 2021 compared to 54% in 2017. Over 75% of hospitals introduced multiple safety-engineered devices (SED), though total replacement occurred in <50% of cases; routine SED availability increased for blood collection (89%) and venous access devices (83%). Incorrect behaviors in handling sharps decreased significantly over time. Nurses' HBV vaccination coverage was high (89% in both surveys); in the last year, 97% were vaccinated against COVID, and 47% against influenza. Average annual injuries per hospital did not increase significantly (32 in 2021 vs. 26 in 2017). In 2017, nurses' perceived safety barriers were working in emergency situations (49%) and lack of resources (40%); in 2021, understaffing (73%), physical fatigue (62%), and handling difficulties while wearing full protective equipment (59%). Safety measures were implemented in Italian hospitals, and although the average injuries per hospital did not show a decrease, these measures could have helped protect healthcare workers during the pandemic, mitigating its potential impact on the increase in situations at risk of injury.

Purpose: Chronic anterior shoulder dislocation represents a rare condition, and there is still lack of consensus in its treatment. Purpose of this study is to evaluate the clinical and radiological outcome of painful locked dislocation underwent shoulder replacement, with a minimum follow-up of two years. Second endpoint is to assess the glenoid bone graft, harvested from the humeral head., Methods: Eight patients underwent shoulder replacement for locked anterior shoulder dislocation. Four patients with a mean age of 23 y.o. were treated with Pyrocarbon-hemiarthroplasty and four patients with a mean age of 76 y.o. were treated with reverse shoulder arthroplasty. Glenoid single stage reconstruction was performed with a bone autograft harvested from the resected humeral head. Patients were observed for a clinical and radiological follow-up for a minimum period of 2 years; ASES and Constant score were assessed., Results: Pain and ROM improvement was reported in all the patients. In one case, postoperative recurrent RSA instability was found. Glenoid reconstruction was performed in seven cases, showing a good integration and no reabsorption issues in all but one cases. ASES and Constant-Murley functional outcomes were rated as excellent by 1 patient with pyrocarbon HA and 1 patient with RSA, good by 3 patients with RSA and 2 patients with HA, fair by 1 patient with HA and poor by one patient with RSA., Conclusion: The treatment of locked anterior glenohumeral dislocation still represents a challenge in symptomatic patients. Shoulder replacement showed good results in young and older patients, with HA and RSA, respectively. Autograft from the humeral head is reliable for glenoid defect, even in ream and run procedure. Locked dislocation lasting more than one year, surgery is debatable for higher risk of a poor outcome and recurrent instability., (© 2021. Istituto Ortopedico Rizzoli.)

Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the colon and small intestine, including Crohn's disease and ulcerative colitis. Since Danio rerio is a promising animal model to study gut function, we developed a soy-dependent model of intestinal inflammation in adult zebrafish. The soya bean meal diet was given for 4 weeks and induced an inflammatory process, as demonstrated by morphological changes together with an increased percentage of neutrophils infiltrating the intestinal wall, which developed between the second and fourth week of treatment. Pro-inflammatory genes such as interleukin-1beta, interleukin-8 and tumour necrosis factor alpha were upregulated in the second week and anti-inflammatory genes such as transforming growth factor beta and interleukin-10. Interestingly, an additional expression peak was found for interleukin-8 at the fourth week. Neuronal genes, OTX1 and OTX2, were significantly upregulated in the first two  weeks, compatible with the development of the changes in the gut wall. As for the genes of the p53 family such as p53, DNp63 and p73, a statistically significant increase was observed after two weeks of treatment compared with controls. Interestingly, DNp63 and p73 were shown an additional peak after four weeks. Our data demonstrate that soya bean meal diet negatively influences intestinal morphology and immunological function in adult zebrafish showing the features of acute inflammation. Data observed at the fourth week of treatment may suggest initiation of chronic inflammation. Adult zebrafish may represent a promising model to better understand the mechanisms of food-dependent intestinal inflammation., (© 2021 The Authors. International Journal of Experimental Pathology published by John Wiley & Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP).)

Introduction: Müller glial cells typically activate to react to hypoxic tissue damage in several retinal diseases. We evaluated the in vitro response to a hypoxia-mimicking stimulus on the expression of a set of genes, known to contribute to eye morphogenesis and cell differentiation., Materials and Methods: A MIO-M1 Müller cell line was cultured in a hypoxia-mimicking environment by the addition of cobalt chloride to the culture medium, followed by a recovery time in which we mimic restoration from the hypoxic insult. The HIF-1 α protein and VEGF-A gene expression were quantified to verify the induction of a hypoxia-like state., Results: Among the genes under study, we did not observe any difference in the expression levels of Otx1 and Otx2 during treatment; conversely, Otx1 was overexpressed during recovery steps. The VEGF-A gene was strongly upregulated at both the CoCl 2 and recovery time points. The transactivated isoform (TA) of the TP73 gene showed an overexpression in long-term exposure to the hypoxic stimulus with a further increase after recovery. Discussion . Our molecular analysis is able to describe the activation of a set of genes, never before described, that can drive the response to a hypoxia-like status. The improved comprehension of these cellular events will be useful for designing new therapeutical approaches for retinal pathologies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Claudio Azzolini et al.)

Objective: Anti-COVID-19 vaccines were mainly associated with non-serious adverse events (AEs), whose prevalence was reported to be up to 70% in healthcare workers (HCWs). This may lead to sick leave requests, but this impact has never been quantified. This study aimed to investigate the absence from work among HCWs following anti-COVID-19 vaccination. Its association with age and previous COVID-19 infection was also assessed., Patients and Methods: This is a retrospective observational cross-sectional study on administrative data about sick leave requests after anti-COVID-19 vaccination. All the HCWs employed at the Niguarda Hospital (Milan, Italy) who received the vaccine from December 27, 2020 to February 28, 2021 were included., Results: In total, 4,088 HCWs received the first dose of the vaccine and 4,043 completed the vaccination cycle. After the first injection, 1.6% of HCWs requested sick leave, while after the second injection, the number of requests significantly increased (+6.1%, p<0.001). A significant increase in sick leave was detected for those who have had SARS-CoV-2 infection after the first injection (+2.3%, p<0.001). After the second dose, a significant increase in sick leave was observed in the 20-30-year-old group compared to >30 years (+3.6%, p=0.017), if HCWs without a history of SARS-CoV-2 infection were considered., Conclusions: The requests for sick leave among HCWs following the anti-COVID-19 vaccine were limited and higher after the second injection. This may help the management of the human resources when the large-scale administration of the anti-COVID-19 vaccines will involve other categories of workers.

Objective: This study aimed to improve the post-marketing surveillance on mRNA anti-SARS-CoV-2 vaccines, characterizing the adverse events (AEs) after the first dose of mRNA BNT162b vaccine. The associations between the AEs and individuals' characteristics were explored., Patients and Methods: All adult healthcare workers at Niguarda Hospital (Milan, Italy) who were referred for the first dose of vaccine were offered to participate in a cross-sectional survey during the second-dose administration, between 18 January and 7 February 2021. All participants completed a questionnaire about age, gender, weight, height, medical history, concurrent therapies, employment status, previous diagnosis/testing for SARS-CoV-2 infection, and a list of 24 AEs (solicited AEs). The development of at least one solicited AEs was the main outcome. AEs were stratified by the presence of injection-site symptoms, systemic symptoms or both, and the differences between strata were assessed as a secondary outcome. Biometric data and reports of a previous diagnosis of SARS-CoV-2 infection were also explored, as predictors of the main outcome., Results: 7,014 healthcare workers were included. An incidence of 3 per 10.000 persons for serious AEs following the first administration of the mRNA BNT162b vaccine was found. An association between the development of non-serious AEs with young age, female gender, low body mass index, and previous history of SARS-CoV-2 was described., Conclusions: This real-life study supported data on the safety profile of the BNT162b2 mRNA vaccine. Our findings on the associations between the development of non-serious AEs with some individual characteristics may help physicians and patients make educated and informed medical decisions towards anti-COVID-19 vaccination.

Background: An isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q), are the most frequent anomalies in the bone marrow of patients with Shwachman-Diamond syndrome, which is caused in most cases by mutations of the SBDS gene. These clonal changes imply milder haematological symptoms and lower risk of myelodysplastic syndromes and acute myeloid leukaemia, thanks to already postulated rescue mechanisms., Results: Bone marrow from fourteen patients exhibiting either the i(7)(q10) or the del(20)(q) and coming from two large cohorts of patients, were subjected to chromosome analyses, Fluorescent In Situ Hybridization with informative probes and array-Comparative Genomic Hybridization. One patient with the i(7)(q10) showed a subsequent clonal rearrangement of the normal chromosome 7 across years. Four patients carrying the del(20)(q) evolved further different del(20)(q) independent clones, within a single bone marrow sample, or across sequential samples. One patient with the del(20)(q), developed a parallel different clone with a duplication of chromosome 3 long arm. Eight patients bore the del(20)(q) as the sole chromosomal abnormality. An overall overview of patients with the del(20)(q), also including cases already reported, confirmed that all the deletions were interstitial. The loss of material varied from 1.7 to 26.9 Mb and resulted in the loss of the EIF6 gene in all patients., Conclusions: Although the i(7)(q) and the del(20)(q) clones are frequent and clinically benign in Shwachman Diamond-syndrome, in the present work we show that they may rearrange, may be lost and then reconstructed de novo, or may evolve with independent clones across years. These findings unravel a striking selective pressure exerted by SBDS deficiency driving to karyotype instability and to specific clonal abnormalities., (© 2021. The Author(s).)

Background: During the last decades, the growing number of shoulder replacement has increased the associated complications. Periprosthetic fractures have a low incidence but can be a severe clinical condition, especially in elderly population. There are still no guidelines to define the best treatment protocol for post-operative periprosthetic humeral fractures. Factors associated to these fractures and consequently the decision-making for the best treatment seem to be patient-related but also correlated with the type of implant. The aim of this study is to analyze the patient's risk factors, fracture pattern, implant type and treatment, evaluating the outcome with a long-term follow-up., Methods: A retrospective study was performed on more than 2700 shoulder prostheses implanted over 10 years in two specialized centers, identifying 19 patients who underwent surgery for post-operative periprosthetic fracture. Gender, age, comorbidities, type of prosthetic implant, type of fracture, and cortical index of each patient were evaluated. All patients underwent surgery and were evaluated with a mean follow-up of 5 years with radiographic controls and functional assessment with the Constant-Murley score., Results: Complete healing was achieved in 18 of 19 patients. All patients presented a lower Constant-Murley score than the pre-fracture score, there were no significant differences between prosthetic implants, and the cortical index was lower than the threshold level in more than 60% of cases., Conclusion: The results of this study showed that a correct preoperative planning is essential to evaluate the type of implant and possible signs of stem mobilization. With a stable stem, it is preferable to maintain it and proceed to a synthesis. The decision process is more complex in periprosthetic fractures with a reduced cortical index, when some radiolucency lines are present in stems with high primary stability, because it is not always indicative of an unstable stem., Level of Evidence: Therapeutic III., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Introduction: Coronal shear fractures of the distal humerus represent an uncommon lesion and could be burdened by high complications. This complex lesion requires an accurate reduction and surgical fixation for a better outcome. Different techniques have been described, however no standard protocol have been proposed. Purpose of this retrospective study, is to evaluate the clinical and radiological outcome with posterior cannulated self-tapping headless screws followed by an early-active-motion protocol and to outline the surgical tips and tricks for different fracture patterns., Materials and Methods: From 2013 to 2019, a consecutive series of 24 patients with coronal shear fracture undergoing ORIF were included in the study. Fractures were classified according to Dubberley's classification. Cannulated self-tapping headless screws were used to fix the fragments. When necessary, additional cannulated half-threaded screws on the lateral edge of the humerus were used, as well as bone chips and fibrin sealant on severe comminution. All patients underwent an assisted early-active-motion rehabilitation protocol. Mean follow-up was 30 months; patients underwent standard X-rays and clinical outcome assessment with range of motion, Broberg and Morrey score and MEPI score., Results: Surgical fixation with headless screw guaranteed complete healing of all shear fractures examined, no loss of reduction were reported. ROM assessment showed good results with an average arc of 113.1°. Excellent to good Broberg-Morrey and MEPI score were reported. No cases of avascular necrosis nor post-traumatic osteoarthritis resulted in our series. Complications occurred in 16.6% of the patients., Conclusion: Coronal shear fracture represents a challenging injury to treat. Anatomical reduction and the use of cannulated self-tapping headless screws from posterior provide a stable fixation, high union rates and good elbow function, with a low cartilage damage and risks of necrosis over 2 years of follow-up., Level of Evidence: Therapeutic III.

Purpose: The aim of this current study was to assess elbow ligament tears after dislocation using magnetic resonance imaging (MRI) and to correlate any pre-operative imaging with intra-operative findings of elbow ligament tears., Methods: We prospectively included 32 patients with acute elbow dislocation investigated by MRI at a means of five days from dislocation. A simple elbow dislocation was diagnosed in 14 patients (44%); associated bone injuries were identified in 18 elbows (56%). Surgical repair of elbow ligaments was carried out in 23 patients, and nine cases were treated non-operatively. A blinded MRI evaluation of all 32 elbows was performed by an orthopaedic surgeon (rater 1) and a musculoskeletal radiologist (rater 2)., Results: Inter-rater agreement for MRI evaluation of 32 was poor for lateral ulnar collateral ligament (LUCL) tears, fair for radial collateral ligament (RCL), moderate for annular ligament (AL), and fair for ulnar collateral ligament (UCL). All tears were reported as complete by rater 1; 13/32 partial tears were identified by rater 2 (LUCL = 2, RCL = 2, UCL = 9). Correlation between surgical and MRI findings showed good inter-rater agreement for LUCL and AL tears in both raters. Agreement for RCL tear was poor for rater 1 and fair for rater 2; agreement for UCL tear was fair for rater 1 and poor for rater 2. Intra-operative findings showed ten radial head fractures (RHFs) and ten coronoid fractures (CFs). LUCL tears were found in the four cases of type II RHFs and in 3/4 cases of CFs. Bone injuries and ligament tears were not significantly associated., Conclusion: MRI scan supported surgeons to identify soft tissue injuries and to address the most suitable surgical approach after acute elbow dislocation. Inter-observer agreement for intra-operative findings was high for LCL complex injuries and poor for UCL.

Background: Inflammatory bowel diseases are associated with remodeling of neuronal circuitries within the enteric nervous system, occurring also at sites distant from the acute site of inflammation and underlying disturbed intestinal functions. Homeoproteins orthodenticle OTX1 and OTX2 are neuronal transcription factors participating to adaptation during inflammation and underlying tumor growth both in the central nervous system and in the periphery. In this study, we evaluated OTX1 and OTX2 expression in the rat small intestine and distal colon myenteric plexus after intrarectal dinitro-benzene sulfonic (DNBS) acid-induced colitis., Methods: OTX1 and OTX2 distribution was immunohistochemically investigated in longitudinal muscle myenteric plexus (LMMP)-whole mount preparations. mRNAs and protein levels of both OTX1 and OTX2 were evaluated by qRT-PCR and Western blotting in LMMPs., Results: DNBS-treatment induced major gross morphology and histological alterations in the distal colon, while the number of myenteric neurons was significantly reduced both in the small intestine and colon. mRNA levels of the inflammatory markers, TNFα, pro-IL1β, IL6, HIF1α and VEGFα and myeloperoxidase activity raised in both regions. In both small intestine and colon, an anti-OTX1 antibody labeled a small percentage of myenteric neurons, and prevalently enteric glial cells, as evidenced by co-staining with the glial marker S100β. OTX2 immunoreactivity was present only in myenteric neurons and was highly co-localized with neuronal nitric oxide synthase. Both in the small intestine and distal colon, the number of OTX1- and OTX2-immunoreactive myenteric neurons significantly increased after DNBS treatment. In these conditions, OTX1 immunostaining was highly superimposable with inducible nitric oxide synthase in both regions. OTX1 and OTX2 mRNA and protein levels significantly enhanced in LMMP preparations of both regions after DNBS treatment., Conclusions: These data suggest that colitis up-regulates OTX1 and OTX2 in myenteric plexus both on site and distantly from the injury, potentially participating to inflammatory-related myenteric ganglia remodeling processes involving nitrergic transmission., Competing Interests: The authors declare that they have no competing interests., (© 2020 Bistoletti et al.)

OTX homeobox (HB) genes are expressed during embryonic morphogenesis and during the development of olfactory epithelium in adult organisms. Mutations occurring in these genes are often related to tumorigenesis in human. No data are available today regarding the possible correlation between OTX genes and tumors of the nasal cavity. The aim of this work is to understand if OTX1 and OTX2 can be considered as molecular markers in the development of nasal tumors. We selected nasal and sinonasal adenocarcinomas to investigate the expression of OTX1 and OTX2 genes through immunohistochemical and real-time PCR analyses.Both OTX1 and OTX2 were absent in all the samples of sinonasal Intestinal-Type Adenocarcinomas (ITACs). OTX1 mRNA was identified only in Non-Intestinal Type Adenocarcinomas (NITACs) while OTX2 mRNA was expressed only in Olfactory Neuroblastomas (ONs). We have demonstrated that the differential gene expression for both OTX1 and OTX2 genes might be a useful molecular marker to distinguish the different types of sinonasal tumors.

Chronic Myeloid Leukemia (CML) is a stem cell cancer that arises when t(9;22) translocation occurs in a hematopoietic stem cells. This event results in the expression of the BCR-ABL1 fusion gene, which codes for a constitutively active tyrosine kinase that is responsible for the transformation of a HSC into a CML stem cell, which then gives rise to a clonal myeloproliferative disease. The introduction of Tyrosine Kinase Inhibitors (TKIs) has revolutionized the management of the disease. However, these drugs do not seem to be able to eradicate the malignancy. Indeed, discontinuation trials (STIM; TWISER; DADI) for those patients who achieved a profound molecular response showed 50% relapsing within 12 months. We performed a comparative analysis on 15 CML patients and one B-ALL patient, between the standard quantitative reverse-transcriptase PCR (qRT-PCR) and our genomic DNA patient-specific quantitative PCR assay (gDNA qPCR). Here we demonstrate that gDNA qPCR is better than standard qRT-PCR in disease monitoring after an average follow-up period of 200 days. Specifically, we statistically demonstrated that DNA negativity is more reliable than RNA negativity in indicating when TKIs therapy can be safely stopped.

Objective: Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF)., Methods: We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000., Results: In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P = 0.023 and P = 0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (≤1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P = 0.007 and P = 0.037, respectively)., Conclusions: Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The hospital risk assessment (VdR) is certainly a relevant issue concerning the activities of prevention for the health of healthcare workers in relation to biological risk. The aim of this paper is to provide an up-date of the issue, based on the suggestions of recent literature about the rules ratified by the new legislative decree and data supplied by the Group of 10 Hospitals participated in this multicenter study. From the analysis of data on healthcare settings (HCS) participating in the project the following considerations can be formulated: i) All HCS considered VdR from biological agents. The method recommended in the Guidelines SIMLII 2005 is the most followed ii) To grading the risk, the use of invasive procedures for carrying out the analysis results is a necessary element iii) the operators classified as exposed to biological risk, and therefore subject to health surveillance, represent almost all of workforce in 7 out of 10 HCS. The subgroup believes that VdR must be conducted in close collaboration with the occupational physician and should represent a worthwhile investment with spin-off character on prevention, decision making, empowering. The presence of environmental requirements and organizational procedures should be considered, so that HCS is enabled for an effective risk management, without which risk assessments cannot be performed. The method of VdR mentioned in the guidelines MLIS 2005, besides being the most widely used by the company participating in the study, still has practical reasons and opportunities to justify its use. The HCS group felt the need to propose an implementation of the definition of invasive procedures and EPP, together with individual assessment. Flexibility was suggested in identifying different levels of risk with the involvement of occupational physicians, especially in the presence of EPP, also in order to plan content and frequency of health surveillance.

Healthcare workers (HCW) are exposed to many different pathogens, and cases of occupational infection have been reported involving the vast majority of known and emerging agents. The risk is present during all the phases of patient care and manipulation of biologic materials, and the implementation of Standard Precautions--and biosafety level 2 measures in the laboratory--and Transmission-Based Precautions in all health settings represents the necessary preventive intervention required by law. Percutaneous exposures represent an extremely frequent event in healthcare facilities; among the many pathogens acquired through this type of exposure, those of highest concern due to the frequency of exposure are HIV, HBV and HCV. Over the last 10 years, though the risk of exposure is still not negligible, occupational infection with HBV has become a rare event; conversely, the incidence of acute C hepatitis became significantly higher among HCW (1,6 per 100.000 inhabitants) with respect to the general population (0,6), with a seroconversion rate following an occupational exposure between 0,5% and 1,8%; finally, reports of occupational HIV infection have decreased, probably also as a secondary beneficial effect of antiretroviral treatment in patients and post-exposure prophylaxis in HCW. The Studio Italiano Rischio Occupazionale da HIV (SIROH) documented from 1986 to 2009 one occupational HBV case, 6 HIV cases (the last one in 2007) and 32 HCV cases. In Europe, the Directive 2010/32/EU approved on May 10 2010 requires Member State to implement within three years a global strategy to prevent occupational exposures in the healthcare setting, particularly with respect to needlestick and sharp injuries, including the adoption, based on risk assessment, of devices incorporating safety features. In Italy the introduction of these devices, according to data collected by the SIROH, showed the possibility to decrease percutaneous exposures by 75%, an effect sustained over time if supported by information, education and training.

Introduction: The influenza illness is a concern for health care workers (HCW) due to the potential nosocomial transmission and sickness absenteeism. Immunization and Isolation Precautions might be effective preventive measures., Aims: To formulate recommendations on vaccination in healthcare settings., Methods: A multidisciplinary working group, led by occupational physicians (OP), examined the information on seasonal influenza immunisation campaign in 9 Italian hospitals in the period 2005-2009 and reviewed scientific evidence., Results: Many health organizations recommend vaccination of HCW. The literature shows that seasonal influenza vaccination of healthy adult have a modest effect in reducing work day lost; there is no evidence that it affects transmission or it prevents the disease in elderly residents. These observations might be conditioned by methodological limitations. Further studies are required to avoid the risk of bias and in pediatric settings. The rate of flu vaccination among HCW is widely variable and it depends on individual risk perception and information about efficacy and side effects. In the considered hospitals, in the five-years period the vaccination rate ranged between 0 and 29%: the median value was 16-17% in 2005, 2008 and 2009 (only against H1N1 influence), 11% and 13% in 2007 and 2006 respectively. OP participation in the vaccination campaign seems to increase the immunization rate., Discussion: Seasonal influenza immunization of HCW might be effective. We recommend to formalize written procedures in health care settings, to perform data computing and to periodically revise immunization activities and promotion and scientific literature, with the aim to appropriately address resources.

Background: Nosocomial transmission of varicella-zoster virus, certain paramixovirus and rubivirus might pose a risk of morbidity for varicella (V), rubella (R), mumps (Mu) and measles (Me) in health care workers (HCW), patients and coworkers. International literature and European legislation recommend preventive interventions to minimize the risk., Methods: A literature review and a seroprevalence study were carried out in 9 hospitals located in north and central Italy, in order to evaluate risk assessment, health surveillance and fitness for work of HCW exposed to V, R, Mu and Me. Antibodies (Ab) against V, R, Mu and Me were determined. For a subgroup of 4 hospitals; sociodemographic, occupational data and sera were collected and analyzed., Results: About 36000 tests on about 9000 HCW were analyzed. Differences in seroprevalence ratios (V 85.7-95.1%, R 47-96.8%, Me 71.4-97.8%, Mu 52.5-87.6%) were detected. In a subgroup, a relevant number of non immune HCW was also found among women infertile age and areas at higher risk. Statistically significant differences were detected only for selected variables and viruses., Discussion and Conclusions: Data of multicenter study confirm literature evidences and allow to define good medical practices for manage and minimize the risk of nosocomial transmission of V, R, Me and Mu. Recommendation are issued about serologic screening on HCW exposed to all 4 viruses thorough the modern analytical techniques, in order to assess risk on individual a group basis and to select priorities for intervention. Vaccination should be prescribed for those HCW non immune, selecting areas and HCW according to priorities.

Introduction: Tuberculosis (TB) is still a threat for healthcare workers (HCW), due to the non decreasing incidence, the spread of drug-resistance, the introduction of new tests for the screening, the relevant costs of surveillance of exposed subjects. These issues implicate a revision of activities to prevent TB in health-care settings., Methods: A multidisciplinary working group, led by occupational physicians, examined the activities to prevent TB performed in 9 Italian hospitals and reviewed the literature, with the aim to formulate evidence-based procedures., Results: In the considered hospitals, 23.000 HCW are classified as exposed to TB, out of 32.000 HCW exposed to biological risks; yearly, about 6000 subjects are screened for preventive, periodical or post-exposure surveillance and 110-130 chemoprophylaxis are prescribed. A high proportion of HCW (54-75%) refused or interrupt to assume the drugs. In the period 2004-2008, 14 occupational TB were diagnosed (9/100.000 HCW exposed to biological risks)., Discussion: Critical issues are the availability of a specific, written TB control plan, including risk assessment, protocols for identifying, evaluating, managing infectious TB patients, health surveillance, education programs, specifically addressed to increase Standard Precaution adoption and compliance to the screening and to adequate risk perception. Risk assessment identify HCW to be included in TB testing (characterized by low positive predictive value), unrecognized TB and environmental control needed; TB risk classification should include no more than 3 or 4 classes and performed by assessing the issues suggested in the Italian guideline. Tubercolin skin test should be used for HCW screening, adding in vitro test in specific circumstances (for example, skin test positivity in BCG vaccinated HCW); the frequency of the screening should not exceed 2 years. Periodical revision of preventive activities should follow up to date scientific literature and need appropriate data computing.

The biological risk from exposure to bloodborne pathogens in health care environments represents a frequent and widespread risk, involving a large number of exposed workers. On the basis of the available scientific innovations, the recent legislation regarding health and safety of workers and the experiences of SIMLII guidelines on health surveillance (HS) workers exposed to biological risk, a multicenter study was carried out, involving nine relevant hospitals and about 32 000 healthcare workers (HCW). A review of the literature was performed, with particular reference to the last 10 years. For each hospital, protocols of HS have been examined according to tasks and biological risk from bloodborne viruses (HBV, HDV, HCV, HIV) as well as management of HCW infected with this pathogens. Differences of risk management in the hospitals, in relationship also with recommendations of the literature have been evaluated. The literature supplies important indications for HS management of HCW exposed to bloodborne pathogens, with relevant information also for patient safety. Preventive examinations are in line with the recommendations of literature and similar across the hospitals for HCV and HIV, while they are different for HBV. Periodic surveillance was different for the frequency, among the hospitals and also as compared to national SIMLII guidelines. As for management, no differentiation among the hospitals was detected as referred to different risk of exposure, while differences were observed around definitions of restrictions. Finally, good medical practices to support occupational physicians in the prevention and management of HCWs' exposed to biological risks are suggested.

Background: The choice of gloves in the healthcare settings is very important because of the high biological and chemical risks present in these workplaces. In order to rationalize and optimize this choice we must balance cost, quality, security and comfort., Objectives: The aim of this study was to analyse the rules in force and to point out the relevant role of the Occupational Health Physician in the right choice and purchase of sanitary gloves., Methods: We reviewed the rules in force and the most relevant studies on these topics., Results and Conclusions: The regulations in force provide that the manufacturers must perform tests to supply evidence for the quality of the products but they do not indicate which analytical method should be used and they do not require that the results are reported in the technical sheets. Thus the manufacturers have only to declare to be "in accordance with the rules". Therefore purchasers should require the manufacturing companies to give detailed information and verify their reliability. Moreover rules could be adapted to higher quality standards. The Occupational Health Physician should suggest the purchase of gloves with high biocompatibility, assuring the protection from the risks of specific tasks and suitable for preventing the onset of new glove-related diseases and the relapses in workers with already diagnosed occupational diseases.

Objective: To evaluate short-term toxicity from and discontinuation of antiretroviral combination prophylaxis in HIV-exposed individuals in Italy., Design: Longitudinal, open study conducted by prospective collection of data in the National Registry of PEP., Setting: All the Italian centres dedicated to HIV related care and licensed by the Ministry of Health to dispense antiretroviral drugs., Study Population: Health care workers and other persons consenting to be treated with post exposure prophylaxis (PEP) after exposures to HIV., Results: Until October, 2000, 207 individuals receiving two nucleoside reverse transcriptase inhibitors (NRTIs), and 354 receiving two NRTIs plus a protease inhibitor (PI) were enrolled. More individuals experienced side-effects in the 3-drug group (53% and 62%, respectively; OR 0.68, (95% CI 0.48-0.98), p < 0.03). However, the proportion of individuals discontinuing prophylaxis because of side-effects did not differ significantly between the 2 groups (21% and 25% respectively; OR 0.82 (95% CI 0.53-1.26); p=0.4). The 43 individuals in the 2 NRTI group discontinued PEP after a mean of 10.4 days of treatment (median 8, range 1-27), similarly to the 88 discontinuations observed in the 3-drug group (mean duration 10.5 days, median 7.5, range 1-26). Type and incidence of specific adverse effects were similar to those reported in the literature., Conclusion: Our study indicates that the difference in the proportion of individuals developing side effects and discontinuing PEP is not significant. The rate of discontinuation because of protease inhibitor side-effects does not justify per se the initial use of a less potent PEP regimen. We suggest initiating PEP with a three-drug regimen and discontinuing the protease inhibitor in the case of adverse effects.

The study was conducted to evaluate neuropsychological symptoms, subjective stress and response speed functions in subjects occupationally exposed to low levels of anesthetic gases. A group of 112 operating theatre personnel exposed to anesthetic gases (nitrous oxide and isoflurane), and 135 non exposed hospital workers from 10 hospitals in Northern Italy were examined before and after the shift on the first and the last day of the working week. Three different tasks were administered: a complex reaction time test (the Stroop Color Word); a questionnaire for neuropsychological symptoms (EURO-QUEST); the block design subtest (WAIS). Biological and atmospheric indicators of exposure were measured. In the exposed group, the geometric mean of urinary nitrous oxide at the end of the shift was 7.1 micrograms/l (95th percentile 12.4, range 1.5-43) on the first and 7.8 micrograms/l (95th percentile 21.5, range 1.0-73.3) on the last day of the working week. On the same days, end of shift urinary isoflurane was 0.7 microgram/l (95th percentile 2.6, range 0-4.7) on the first day and 0.8 microgram/l (95th percentile 2.0, range 0-5.6) on the last. The exposed and control subjects were comparable for both basic intellectual abilities and subjective stress levels. No statistical differences were observed between exposed and control subjects for neuropsychological tests and symptoms. No dose-effect relationships were observed between the exposure indicators and the test results. In conclusion, no early behavioral effect on the central nervous system was detectable at the exposure levels measured. The biological exposure limits of 13 micrograms/l for nitrous oxide and 1.8 micrograms/l for isoflurane corresponding respectively to the atmospheric concentrations of 25 ppm and 0.5 ppm seem to be adequately protective for the integrity of workers' neurobehavioral functions, as measured with the tests used.

Unlike other apparatuses, the potential effects on the nervous system of occupational exposure to anaesthetic gases have not been exhaustively reviewed. Because of the relevance of these effects, their significance of the quality of life of the exposed subjects and of the increased risk inherent in their delicate work tasks, these themes deserve the greatest attention. This paper briefly examines the data from the international literature as well as the neurobehavioral methods employed, underlines the existing gaps of knowledge and eventually proposes strategies aimed at filling these gaps of knowledge.