Generalizability of a Musculoskeletal Therapist Electronic Health Record for Modelling Outcomes to Work-Related Musculoskeletal Disorders.

PURPOSE: Electronic Health Records (EHRs) can contain vast amounts of clinical information that could be reused in modelling outcomes of work-related musculoskeletal disorders (WMSDs). Determining the generalizability of an EHR dataset is an important step in determining the appropriateness of its reuse. The study aims to describe the EHR dataset used by occupational musculoskeletal therapists and determine whether the EHR dataset is generalizable to the Australian workers' population and injury characteristics seen in workers' compensation claims. METHODS: Variables were considered if they were associated with outcomes of WMSDs and variables data were available. Completeness and external validity assessment analysed frequency distributions, percentage of records and confidence intervals. RESULTS: There were 48,434 patient care plans across 10 industries from 2014 to 2021. The EHR collects information related to clinical interventions, health and psychosocial factors, job demands, work accommodations as well as workplace culture, which have all been shown to be valuable variables in determining outcomes to WMSDs. Distributions of age, duration of employment, gender and region of birth were mostly similar to the Australian workforce. Upper limb WMSDs were higher in the EHR compared to workers' compensation claims and diagnoses were similar. CONCLUSION: The study shows the EHR has strong potential to be used for further research into WMSDs as it has a similar population to the Australian workforce, manufacturing industry and workers' compensation claims. It contains many variables that may be relevant in modelling outcomes to WMSDs that are not typically available in existing datasets.

Electronic Health Records for Predicting Outcomes to Work-Related Musculoskeletal Disorders: A Scoping Review.

PURPOSE: Through electronic health records (EHRs), musculoskeletal (MSK) therapists such as chiropractors and physical therapists, as well as occupational medicine physicians could collect data on many variables that can be traditionally challenging to collect in managing work-related musculoskeletal disorders (WMSDs). The review's objectives were to explore the extent of research using EHRs in predicting outcomes of WMSDs by MSK therapists. METHOD: A systematic search was conducted in Medline, PubMed, CINAHL, and Embase. Grey literature was searched. 2156 unique papers were retrieved, of which 38 were included. Three themes were explored, the use of EHRs to predict outcomes to WMSDs, data sources for predicting outcomes to WMSDs, and adoption of standardised information for managing WMSDs. RESULTS: Predicting outcomes of all MSK disorders using EHRs has been researched in 6 studies, with only 3 focusing on MSK therapists and 4 addressing WMSDs. Similar to all secondary data source research, the challenges include data quality, missing data and unstructured data. There is not yet a standardised or minimum set of data that has been defined for MSK therapists to collect when managing WMSD. Further work based on existing frameworks is required to reduce the documentation burden and increase usability. CONCLUSION: The review outlines the limited research on using EHRs to predict outcomes of WMSDs. It highlights the need for EHR design to address data quality issues and develop a standardised data set in occupational healthcare that includes known factors that potentially predict outcomes to help regulators, research efforts, and practitioners make better informed clinical decisions.

SARS-CoV-2 caused a surge in antibiotic consumption causing a silent pandemic inside the pandemic. A retrospective analysis of Italian data in the first half of 2022.

BACKGROUND: The phenomenon of antibiotic resistance shows no sign of stopping, despite global policies to combat it that have been in place for several years. The risk of forms of pathogenic microorganisms that are increasingly resistant to common antibiotics has led health authorities around the world to pay greater attention to the phenomenon. The worrying situation, has led to further recommendations from the World Health Organization (WHO) and national recommendations in Italy through the new National Plan against Antibiotic Resistance 2022-2025 (PNCAR 2022-2025). AIM: This manuscript aims to raise the awareness of all health professionals to follow what is suggested by regulatory agencies and scientific societies. METHOD: We conducted a retrospective study of antibiotic pharmacoutilization in Italy, in the Campania region at the Azienda Sanitaria Locale (ASL) Napoli 3 Sud, on consumption in the first half of 2022 in a population of more than 1 million people. RESULT: The results indicate that consumption, based on defined daily doses (DDDs), is above the national average. Probably the COVID-19 pandemic has influenced this growth in prescriptions. CONCLUSIONS: Our study suggests an informed and appropriate use of antibiotics, so as to embark on a virtuous path in the fight against antibiotic resistance.

COVID-19 vaccines and decreased transmission of SARS-CoV-2.

A massive COVID-19 vaccination campaign is underway worldwide. Epidemiological data from studies indicate excellent efficacy and safety profile for COVID-19 vaccines. However, there are few data from studies on the effect of decreasing the probability of infection of vaccinated subjects compared to unvaccinated subjects. In this short communication, we describe some evidence on this important and current topic providing useful personal reflections.

Gastric emptying after sleeve gastrectomy: statistical evidence of a controlled prospective study with gastric scintigraphy.

AIM: Laparoscopic sleeve gastrectomy (LSG) is a stand-alone bariatric procedure, its feasibility and efficacy being confirmed by long-term data. The effect of the procedure is believed to be based on the gastric restriction and reduction of ghrelin. Nevertheless it remains still controversial the role of LSG on gastric emptying and the impact that this may have on weight loss outcomes. Our aim is to assess gastric emptying after LSG using gastric scintigraphy. METHODS: For this prospective randomized study, 45 patients undergoing LSG at our Centre for the Multidisciplinary Treatment of Severe Obesity from April 2009 to April 2011 were enrolled and observed prospectively (Group A). The inclusion criteria followed the guidelines for bariatric surgery. All patients performed gastric emptying scintigraphy through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc 99. Group A performed the exam before (A1) and after the operation (A2). A control group (Group B) included 20 patients undergoing scintigraphic assessment for other reasons. RESULTS: LSG was performed following a standardized technique. No complications were observed. The scintigraphic study showed a reduced half-life tracer (A1 vs. A2: 80.4±16.5 min vs. 64.3±22 min P=0.06), without a significant difference. Comparing the two groups no differences occurred before operation (B vs. A1). Gastric emptying time resulted significatively reduced in group A2 rather than in group A1 and B. CONCLUSION: Gastric motility plays a role in the pathogenesis of obesity. Our experience suggests that LSG reduces gastric emptying time, but further studies are necessary to reach statystical significativity.

Positive findings in preoperative testing prior to gastric banding: their real value.

AIM: Relations between laparoscopic adjustable gastric banding (LAGB), gastroesophageal reflux (GER) and hiatal hernia (HH) are controversial. In this context the role of preoperative investigations to assess upper gastrointestinal (GI) function and its impact on the approach to LAGB and outcomes remains unclear. The aim was to define the value of preoperative upper GI testing, and to relate the findings with postoperative outcomes. METHODS: Seventy-eight cases were enrolled among 250 patients undergoing LAGB from January 2010 to December 2011 in our Center for the Multidisciplinary treatment of severe obesity. Patients were submitted preoperatively to endoscopy and radiologic series with oral contrast to assess the state of upper GI mucosa, the presence of HH, GER or cardias incontinence. According to the findings, patients were assigned to group A, if one or both exams showed positive results; or to the control group B if both exams were negative. RESULTS: GI series showed GER in 14.1% of patients, HH in 6.4%, altered motility in 5.1%, gastritis in 3.1%and were negative in 75.6%. Endoscopy showed gastritis in 71.8%of patients, HH in 30.8%, esophagitis in 7.7%, duodenitis in 7.7%, LES incontinence in 8%; while only 21.8% of patients had a negative exam. Differences between group A and B are not statistically significant in terms of pre- and post-operative BMI, EBWL%, long-term complications, time and number of regulations. CONCLUSION: Positive findings in preoperative testing rarely postpone or change the surgical approach and postoperative outcomes. Our results encourage the omission of upper GI series from routine evaluation protocol prior to LAGB.

Association between microbiota and immune response to Sars-CoV-2 infection.

In recent times, the key role of the human microbiota in the body's response to infectious diseases has been increasingly demonstrated. The human microbiota is the set of symbiotic microorganisms which coexist with the human organism without harming it. However, diseases related to the microbiota occur and are being studied, and numerous publications suggest that altered microbiota composition is implicated in psychiatric diseases, chronic inflammatory diseases, and some viral infections. On the other hand, the role of the human microbiota in the host immune response to viral infections is not entirely clear. Metabolites or components produced by the microbiota are the main mediators of microbiota-host interactions that influence host immunity. It has been shown that in patients with COVID-19 and post-acute COVID-19 syndrome (PACS), the microbiota is significantly altered. In this brief review, we examine the associations between the role of the microbiota in response to COVID-19 infection in terms of molecular biology and clinical relevance. We finally discuss the mechanisms by which metabolites produced by the microbiota modulate host immune responses to SARS-CoV-2 infection.

Scientific Hypothesis for Treatment of COVID-19's Lung Lesions by Adjusting ACE/ACE2 Imbalance.

In March 2019 began the global pandemic COVID-19 caused by the new Coronavirus SARS-CoV-2. The first cases of SARS-CoV-2 infection occurred in November-19 in Wuhan, China. The preventive measures taken did not prevent the rapid spread of the virus to all countries around the world. To date, there are about 2.54 million deaths, effective vaccines are in clinical trials. SARS-CoV-2 uses the ACE-2 protein as an intracellular gateway. ACE-2 is a key component of the Renin Angiotensin (RAS) system, a key regulator of cardiovascular function. Considering the key role of ACE-2 in COVID-19 infection, both as an entry receptor and as a protective role, especially for the respiratory tract, and considering the variations of ACE-2 and ACE during the stages of viral infection, it is clear the important role that the pharmacological regulation of RAS and ACE-2 can assume. This biological knowledge suggests different pharmacological approaches to treat COVID-19 by modulating RAS, ACE-2 and the ACE/ACE2 balance that we describe in this article.

Pharmacological approach for the reduction of inflammatory and prothrombotic hyperactive state in COVID-19 positive patients by acting on complement cascade.

The novel Coronavirus SARS-CoV-2 is the viral pathogen responsible for the ongoing global pandemic, COVID-19 (Coronavirus disease 2019). To date, the data recorded indicate 1.62 Mln deaths and 72.8 Mln people infected (WHO situation report Dec 2020). On December 27, the first anti-COVID-19 vaccinations started in Europe. There are no direct antivirals against SARS-CoV-2. Understanding the pathophysiological and inflammatory/immunological processes of SARS-CoV-2 infection is essential to identify new drug therapies. In the most severe COVID-19 cases, an unregulated immunological/inflammatory system results in organ injury that can be fatal to the host in some cases. Pharmacologic approaches to normalize the unregulated inflammatory/immunologic response is an important therapeutic solution. Evidence associates a non-regulation of the "complement system" as one of the causes of generalized inflammation causing multi-organ dysfunction. Serum levels of a complement cascade mediator, factor "C5a", have been found in high concentrations in the blood of COVID-19 patients with severe disease. In this article we discuss the correlation between complement system and COVID-19 infection and pharmacological solutions directed to regulate.

Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex.

Transgenic murine lines have been constructed that express a chimeric class I molecule composed of the alpha 1 and alpha 2 domains of HLA-A2.1 and the alpha 3, transmembrane, and cytoplasmic domains of H-2Kb. Upon immunization with influenza virus, transgenic mice developed a strong A2.1Kb-restricted cytotoxic T lymphocyte (CTL) response specific for the same matrix protein epitope that serves as the dominant A2.1-restricted determinant in the equivalent human response. Fine specificity analysis of CTL clones using truncated peptides revealed strong similarity between the response repertoire of transgenic mice and that previously reported using influenza-specific A2.1-restricted CTL clones from humans. This suggests that even when considering T cell responses by different species, the alpha 1 and alpha 2 domains of the restriction element play a dominant role in determining the CTL specific repertoire. Thus, substituting the alpha 3 domain of A2.1 with a murine counterpart has permitted development of a transgenic strain that should serve as an excellent model system in studies of HLA-restricted responses.

Pharmacological agents to therapeutic treatment of cardiac injury caused by Covid-19.

SARS-CoV-2 is responsible for the 2019 coronavirus disease (COVID-19), a global pandemic that began in March 2020 and is currently in progress. To date, COVID-19 has caused about 935,000 deaths in more than 200 countries. The respiratory system is most affected by injuries caused by COVID-19, but other organs may be involved, including the cardiovascular system. SARS-CoV-2 penetrates host cells through the angiotensin 2 conversion enzyme (ACE-2). ACE-2 is expressed not only in the lungs, but also in other organs, including the cardiovascular system. Several studies have found that a good percentage of patients with severe COVID-19 have cardiac lesions, including myocardial fibrosis, edema and pericarditis. Pathological remodeling of the extracellular matrix caused by viral infection leads to myocardial fibrotic lesions. These fibrotic scars can cause cardiac dysfunction, reducing the ejection fraction caused by the presence of stiffened myocardial matrix, or cardiac arrhythmias that cause an alteration in the electrical conduction system of the heart. These cardiac dysfunctions can cause death. It is therefore essential to identify cardiac involvement early in order to act with appropriate therapeutic treatments. In this review, we describe what is known about cardiac injury from COVID-19, highlighting effective pharmacological therapeutic solutions to combat cardiac injury, particularly cardiac fibrosis, caused by COVID-19.

The role of beta 2-microglobulin in peptide binding by class I molecules.

Efficient transport of class I major histocompatibility complex molecules to the cell surface requires association of the class I heavy chain with endogenous peptide and the class I light chain, beta 2-microglobulin (beta 2M). A mutant cell line deficient in beta 2M transports low amounts of nonpeptide-associated heavy chains to the cell surface that can associate with exogenously provided beta 2M and synthetic peptide antigens. Normal beta 2M-sufficient cells grown in serum-free media devoid of beta 2M also require an exogenous source of beta 2M to efficiently bind synthetic peptide. Thus, class I molecules on normal cells do not spontaneously bind or exchange peptides.

Impaired immunoproteasome assembly and immune responses in PA28-/- mice.

In vitro PA28 binds and activates proteasomes. It is shown here that mice with a disrupted PA28b gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in PA28-/- mice. Cytotoxic T lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.

Rheumatoid arthritis, Klippel-Feil syndrome and Pott's disease in Cardinal Carlo de' Medici (1595-1666).

OBJECTIVE: A paleopathological study was carried out on the she skeletal remains of Cardinal Carlo de' Medici (1595-1666), son of the Grand Duke Ferdinando I (1549-1609) and Cristina from Lorraine (1565-1636), to investigate the articular pathology described in the archival sources. METHODS: The skeletal remains of Carlo, buried in the Basilica of San Lorenzo in Florence, have been exhumed and submitted to macroscopic and radiological examination. RESULTS: The skeleton of Carlo revealed a concentration of different severe pathologies. Ankylosis of the cervical column, associated with other facial and spine anomalies suggests a diagnosis of congenital disease: the Klippel-Feil syndrome. In addition, the cervical segment presents the results of the tuberculosis (Pott's disease) from which the Cardinal suffered in his infancy. The post-cranial skeleton shows an ankylosing disease, mainly symmetrical and extremely severe, involving the large as well as small articulations, and characterized by massive joint fusion, that totally disabled the Cardinal in his last years of life. CONCLUSIONS: The final diagnosis suggests an advanced, ankylosing stage of rheumatoid arthritis.

Comparison between LigaSure™ and Harmonic® in Laparoscopic Sleeve Gastrectomy: A Single-Center Experience on 422 Patients.

Background: New laparoscopic devices, such as electrothermal bipolar-activated devices (LigaSure™ (LS)) or ultrasonic systems (Harmonic® scalpel (HS)), have been applied recently to bariatric surgery allowing to reduce blood loss and surgical risks. The aim of this study was to retrospectively compare intraoperative performance of HS and LS, postoperative results, and clinical outcomes in a large cohort of patients undergoing LSG. Methods: Data from 422 morbidly obese patients undergoing LSG in our Bariatric Unit at the Advanced Biomedical Sciences Department of the "Federico II" University of Naples (Italy) between January 2009 and December 2017 were retrospectively analyzed. Subjects were divided into two groups (HS and LS), and operative time, intraoperative complications, and postoperative (within 30 days from surgery) complications were compared. Bleeding from the omentum or from the staple line, use of hemostatic clips, and absorbable hemostat were recorded as intraoperative complications; hemorrhages, abscess formation, gastric leaks, fever, and mortality were considered as postoperative complications. Results: Statistical analysis showed no difference in terms of baseline demographics between the two cohorts. Operative time (48 ± 9 vs 49 ± 6 min, p=0.646) and the rates of intraoperative and postoperative complications did not significantly differ between groups. Conclusion: Harmonic® and LigaSure™ are both useful tools in bariatric surgery, and these two advanced power devices are user-friendly and can facilitate surgeon work; from this point of view, the choice of the energy device should be based on the preference of the surgeon and on the hospital costs policy and availability.

IFSO Worldwide Survey 2016: Primary, Endoluminal, and Revisional Procedures.

BACKGROUND AND AIM: The International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), being a Federation of 62 national societies, is the ideal network to monitor the number and type of procedures at a global level. The IFSO survey, enriched with a special section on revisional procedures, aims to report the number and types of bariatric procedures performed worldwide in 2016 and analyzes the surgical trends from 2008 to 2016. METHODS: The 2016 IFSO Survey form was emailed to all IFSO societies. Each Society was requested to indicate the number and type of bariatric procedures performed in the country. Trend analyses from 2008 to 2016 were also performed. RESULTS: The total number of bariatric/metabolic procedures performed in 2016 was 685,874; 634,897 (92.6%) of which were primary and 50,977 were revisional (7.4%). Among the primary interventions, 609,897 (96%) were surgical and 25,359 (4%) were endoluminal. The most performed primary surgical bariatric/metabolic procedure was sleeve gastrectomy (SG) (N = 340,550; 53.6%), followed by Roux-en-Y gastric bypass (N = 191,326; 30.1%), and one-anastomosis gastric bypass (N = 30,563; 4.8%). CONCLUSIONS: In 2016, there was an increase in the total number both of surgical and endoluminal bariatric/metabolic procedures. Revisional procedures represent about 7% of the total bariatric interventions. SG remains the most performed surgical procedure in the world.

Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.

Our goal is to use peptide epitopes that are recognized by cytotoxic T lymphocytes (CTL) as immunogens for the development of prophylactic and therapeutic vaccines with chronic hepatitis B virus (HBV) infection being our first therapeutic target. Because most CTL peptide epitopes are poor immunogens, we specifically modified them by covalently attaching two additional components: a T helper peptide epitope and two lipid molecules. Using the murine influenza virus CTL epitope NP 147-155 as a model system, we found this construct to be highly immunogenic, and a single injection resulted in memory CTL induction that persisted for > 1 yr. Based on the animal studies, a vaccine was designed and tested for both safety and its ability to induce a primary CTL response in normal subjects. The three vaccine components included HBV core antigen peptide 18-27 as the CTL epitope, tetanus toxoid peptide 830-843 as the T helper peptide, and two palmitic acid molecules as the lipids. A dose escalation trial (5, 50, and 500 micrograms) carried out in 26 normal subjects showed that the vaccine was safe and able to induce a primary HBV-specific CTL response. A dose-response curve was observed and five out of five subjects responded to the 500-micrograms dose.

Application of an artificial neural network to predict specific class I MHC binding peptide sequences.

Computational methods were used to predict the sequences of peptides that bind to the MHC class I molecule, K(b). The rules for predicting binding sequences, which are limited, are based on preferences for certain amino acids in certain positions of the peptide. It is apparent though, that binding can be influenced by the amino acids in all of the positions of the peptide. An artificial neural network (ANN) has the ability to simultaneously analyze the influence of all of the amino acids of the peptide and thus may improve binding predictions. ANNs were compared to statistically analyzed peptides for their abilities to predict the sequences of K(b) binding peptides. ANN systems were trained on a library of binding and nonbinding peptide sequences from a phage display library. Statistical and ANN methods identified strong binding peptides with preferred amino acids. ANNs detected more subtle binding preferences, enabling them to predict medium binding peptides. The ability to predict class I MHC molecule binding peptides is useful for immunolological therapies involving cytotoxic-T cells.