Response to COVID-19 in Cyprus: Policy changes and epidemic trends.

OBJECTIVES: In late July, Cyprus experienced the second epidemic wave of COVID-19. We present the steps taken by the government and evaluate their effect on epidemic trends. MATERIALS: Cyprus Press and Information Office data were analysed. Using an R-based forecasting program, two models were created to predict cases up to 01/09/2020: Model 1, which utilised data up to 09/06/2020, when airports reopened to foreign travelers with COVID-19 screening; and Model 2, which utilised data until 24/06/2020, when screening for passengers from low-transmission countries was discontinued. RESULTS: PIO data revealed no significant policy changes between 24/06/2020 and 31/07/2020. Prediction models were robust and accurate (Model 1, R2  = 0.999, P < .001; Model 2, R2  = 0.998, P < .001). By August 30th, recorded cases exceeded those predicted by Model 1 by 24.47% and by Model 2 by 20.95%, with P values <.001 for both cases. CONCLUSIONS: The significant difference between recorded cases and those projected by Models 1 and 2 suggests that changes in epidemic trends may have been associated with policy changes after their respective dates. Discontinuation of major restrictions such as airport reopening, can destabilise the control of the epidemic, and may concomitantly necessitate a reevaluation of the current epidemic status. In the face of an evolving situation such as the COVID-19 pandemic, states are forced to balance the imposing of restrictions against their impact on the economy.

Paraneoplastic Arthritides: Insights to Pathogenesis, Diagnostic Approach, and Treatment.

ABSTRACT: Paraneoplastic arthritides are a group of inflammatory rheumatic syndromes induced by an occult and manifest malignancy, characterized by a wide range of musculoskeletal signs and symptoms that masquerade other rheumatic diseases such as rheumatoid arthritis. Although the pathogenesis of paraneoplastic arthritides is unknown, immune-mediated mechanisms can induce a paraneoplastic syndrome, with a dominant feature the polyarthritis. Common entities of paraneoplastic arthritides include paraneoplastic polyarthritis, hypertrophic osteoarthropathy, remitting seronegative symmetrical synovitis with pitting edema, palmar fasciitis and polyarthritis, and polyarthritis and panniculitis associated with pancreatic carcinoma. The electronic databases PubMed and Scopus were scrutinized using the following terms: paraneoplastic arthritis, paraneoplastic polyarthritis, or paraneoplastic rheumatic diseases. Abstracts, full articles, and selected references were reviewed. The aim of the present narrative review article was to describe the clinical characteristics, diagnostic evaluation, and management of paraneoplastic arthritides, and highlight the challenges that health care providers may encounter, distinguishing those conditions from other autoimmune rheumatic disorders. Future studies are needed to give insight into the mechanisms associated with paraneoplastic arthritides, leading to the development of novel diagnostic biomarkers.

Infection-induced myeloperoxidase specific antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis: A systematic review.

BACKGROUND: We conducted a systematic review to identify cases of infection-induced anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: PubMed/Medline databases were searched from inception to July of 2020, according to PRISMA guidelines. RESULTS: Among the 618 abstracts identified, 18 articles describing 23 patients (60.9% female, mean age 50.5 years) were included. Median time between infection and vasculitis development was 3 months. Five (21.7%) patients expired during follow-up. Vasculitis regressed after the resolution of infection in 12/23 (52.2%). ANCA titers decreased significantly on follow-up in 14/16 patients and in all survivors in which they were measured. Pathogens reported included Mycobacterium spp., Coccidioides spp., Rickettsia rickettsii, Staphylococcus spp., EBV, CMV and Dengue virus. CONCLUSIONS: MPO-AAV can occur after infection and may regress after its resolution. Infection should be considered in cases of MPO-AAV, as immunosuppressive treatment can have catastrophic results if the infection is not adequately treated.

Measles-associated pneumonia and hepatitis during the measles outbreak of 2018.

Background Between 2017 and 2018, Greece experienced a measles outbreak, affecting >3000 patients, most of which were unvaccinated. Measles-associated pneumonia (MAP) is the most common serious compilation of the disease, but very few recent reports regarding its presentation are available. Materials and Methods Between January and May 2018, 11 adult patients presented to our department with acute measles virus infection, hypoxia and findings on chest X-ray. Clinical, laboratory and radiological data were collected and assessed. Nine out of eleven patients had hypoxic respiratory failure. Other complications included hepatitis, cholestasis and myositis, which were observed in the majority of patients. All patients received supplementary oxygen administration, whereas five patients required continuous positive airway pressure ventilation. Scoring of the radiological examinations performed was most notable for the presence of reticular opacities and consolidations. Statistical analysis demonstrated a significant association between PaO2/FiO2 values and the presence of reticular opacities, with PaO2/FiO2 decreasing as the mean value of the reticular opacities score increased (P = .02). Conclusion To our knowledge, this is the first report demonstrating an association between PaO2/FiO2 values and the presence of reticular opacities in patients with MAP. MAP should be suspected in any patient presenting with acute onset hypoxaemia and a reticular pattern on radiological examination, especially in outbreak settings. What is known Measles infections are on the rise in Europe, with epidemics affecting several European countries, resulting from suboptimal immunisation. The most common serious complication of measles is pneumonia, which is more common in adult patients and can cause significant morbidity. It is the most common cause of death due to measles. What is new In this report, we present 11 adults with measles-associated pneumonia, who presented with the combination of acute measles virus infection, hypoxia and findings on chest X-ray. To our knowledge, this is the first report demonstrating an association between the severity of hypoxaemia and the presence of reticular opacities on chest imaging studies.

Effect of HIV-1 subtype and tropism on treatment with chemokine coreceptor entry inhibitors; overview of viral entry inhibition.

HIV-1 entry begins with viral envelope glycoprotein gp120 interacting with host-cell CD4 and an entry coreceptor (mainly chemokine receptors CCR5 or CXCR4). Inhibitors of particular coreceptors are being developed in order to exploit this step of cellular infection. However, effectiveness of these drugs requires matching of the administered therapeutic to coreceptor use by the viral variants infecting each patient. Patient viruses may use only CCR5 (R5), only CXCR4 (X4) or both (D/M). Most patients in early disease have R5 variants, with the presence of X4 variants increasing as disease progresses; the infecting subtype also affects the prevalence of X4 variants. Phenotypic, genotypic and clinical trial tests are in use to determine coreceptor utilization by HIV-1 variants, termed tropism, and to predict the response to entry inhibitors. Maraviroc is the only approved entry-coreceptor inhibitor and inhibits CCR5-gp120 interaction. Clinical trials of maraviroc in specific patient subgroups are elucidating the drug's role in contemporary clinical practice. Treatment failure to this and other CCR5 inhibitors has been shown to result from either outgrowth of X4 variants or through resistance mutations leading to R5 variants that are able to enter cells using drug-bound CCR5; thus, new entry inhibitors seek to circumvent this mechanism of resistance.

Epidemiology of Hantavirus infections in humans: a comprehensive, global overview.

Hantaviruses comprise an emerging global threat for public health, affecting about 30,000 humans annually. Infection may lead to Hantavirus pulmonary syndrome (HPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in the Europe and Asia. Humans are spillover hosts, acquiring infection primarily through the inhalation of aerosolized excreta from infected rodents and insectivores. Risk factors for infection include involvement in outdoor activities, such as rural- and forest-related activities, peridomestic rodent presence, exposure to potentially infected dust and outdoor military training; prolonged, intimate contact with infected individuals promotes transmission of Andes virus, the only Hantavirus known to be transmitted from human-to-human. The total number of Hantavirus case reports is generally on the rise, as is the number of affected countries. Knowledge of the geographical distribution, regional incidence and associated risk factors of the disease are crucial for clinicians to suspect and diagnose infected individuals early on. Climatic, ecological and environmental changes are related to fluctuations in rodent populations, and subsequently to human epidemics. Thus, prevention may be enhanced by host-reservoir control and human exposure prophylaxis interventions, which likely have led to a dramatic reduction of human cases in China over the past decades; vaccination may also play a role in the future.

Bronchoscopy-related outbreaks and pseudo-outbreaks: A systematic review.

OBJECTIVE: To identify and report the pathogens and sources of contamination associated with bronchoscopy-related outbreaks and pseudo-outbreaks. DESIGN: Systematic review. SETTING: Inpatient and outpatient outbreaks and pseudo-outbreaks after bronchoscopy. METHODS: PubMed/Medline databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the search terms "bronchoscopy," "outbreak," and "pseudo-outbreak" from inception until December 31, 2022. From eligible publications, data were extracted regarding the type of event, pathogen involved, and source of contamination. Pearson correlation was used to identify correlations between variables. RESULTS: In total, 74 studies describing 23 outbreaks and 52 pseudo-outbreaks were included in this review. The major pathogens identified in these studies were Pseudomonas aeruginosa, Mycobacterium tuberculosis, nontuberculous mycobacteria (NTM), Klebsiella pneumoniae, Serratia marcescens, Stenotrophomonas maltophilia, Legionella pneumophila, and fungi. The primary sources of contamination were the use of contaminated water or contaminated topical anesthetics, dysfunction and contamination of bronchoscopes or automatic endoscope reprocessors, and inadequate disinfection of the bronchoscopes following procedures. Correlations were identified between primary bronchoscope defects and the identification of P. aeruginosa (r = 0.351; P = .002) and K. pneumoniae (r = 0.346; P = .002), and between the presence of a contaminated water source and NTM (r = 0.331; P = .004) or L. pneumophila (r = 0.280; P = .015). CONCLUSIONS: Continued vigilance in bronchoscopy disinfection practices remains essential because outbreaks and pseudo-outbreaks continue to pose a significant risk to patient care, emphasizing the importance of stringent disinfection and quality control measures.

Powassan Virus Infections: A Systematic Review of Published Cases.

BACKGROUND: Powassan virus is an emerging neurotropic arbovirus transmitted by the tick Ixodes scapularis. This systematic review was conducted to aggregate data on its clinical manifestations, diagnostic findings, and complications. METHODS: PubMed was searched until August 2023 using the term "Powassan", to identify all published cases of Powassan virus infections, as per PRISMA guidelines. RESULTS: Among the 380 abstracts identified, 45 studies describing 84 cases (70 adult, 14 pediatric) were included. Cases were reported from the USA and Canada. Complications included paralysis in 44.1% of adult and 42.6% of pediatric cases, cognitive deficits in 33.3% of adult and 25% of pediatric cases, while the mortality rate was 19.1% and 7.1% in the adult and pediatric populations, respectively. Correlation analysis revealed an association between mortality and age (r = 0.264, p = 0.029), development of paralysis (r = 0.252, p = 0.041), or respiratory distress or failure (r = 0.328, p = 0.006). Factors associated with persistent neurological deficits were development of ataxia (r = 0.383, p = 0.006), paralysis (r = 0.278, p = 0.048), speech disorder (r = 0.319, p = 0.022), and cranial nerve involvement (r = 0.322, p = 0.017). Other significant correlations included those between speech disorders and ataxia (r = 0.526, p < 0.001), and between paralysis and respiratory distress or failure (r = 0.349, p = 0.003). CONCLUSION: Powassan virus infections have significant morbidity and mortality and should be suspected in cases of encephalitis and possible tick exposure. PROSPERO registration number: CRD42023395991.

Red man syndrome adverse reaction following intravenous infusion of cefepime.

We report the first case of cefepime-induced "red-man syndrome," which appeared 30 min following drug infusion and was confirmed with a rechallenge test. This syndrome is classically associated with vancomycin infusion and is the result of non-IgE mediated mast cell degranulation. While this adverse effect can be easily managed with drug withdrawal and antihistamine administration, it is unknown whether it can be prevented with slower cefepime infusion and preinfusion antihistamines, as is the case with vancomycin.

Hantavirus infections for the clinician: from case presentation to diagnosis and treatment.

Hantaviruses cause Hantavirus Pulmonary Syndrome (HPS; also called Hantavirus Cardiopulmonary Syndrome) in the Americas and Hemorrhagic Fever with Renal Syndrome (HFRS) in Asia and Europe. In Scandinavia and northern Europe, a milder form of HFRS is prevalent, termed nephropathica epidemica (NE). HPS presents with acute respiratory failure, mild-moderate renal failure, thrombocytopenia, and reactive lymphocytosis. HFRS has pronounced renal dysfunction and less prominent respiratory involvement, with thrombocytopenia and hemorrhagic findings. Both syndromes have long-term sequelae. Common symptomatology is due to underlying pathophysiology, mainly increased vascular permeability and immune activation. Laboratory and imaging markers predicting disease severity are under research, allowing for more efficient patient management. Diagnosis is presumptive, based on typical clinical findings and patient history of likely rodent exposure. Confirmation of diagnosis is by serological testing and/or RT-PCR. Treatment is mainly comprised of cardiovascular, respiratory, and renal function support, with fluid and electrolyte homeostasis being crucial components of care. In HPS, the use of extracorporeal membrane oxygenation in decompensated patients has also shown to be beneficial.

Postoperative sepsis after colorectal surgery: a prospective single-center observational study and review of the literature.

Introduction: Postoperative sepsis represents a significant problem in colorectal surgery patients. Aim: To identify the etiology as well as the risk factors associated with the development of postoperative sepsis, based on prospective data of patients undergoing colorectal surgery at a single large-volume institution. Material and methods: Between November 2019 and February 2021, 141 patients underwent an elective operation for colorectal cancer at a tertiary hospital center. The following variables were recorded for each patient: age, gender, American Society of Anesthesiologists Classification (ASA class), duration of surgery, surgical approach, comorbidities (diabetes, cardiovascular disease, respiratory disease). Univariate analysis was performed using χ2 tests for categorical variables. Results: A total of 69 males and 72 females were enrolled. Postoperative sepsis was diagnosed in 18 (12.77%) cases, with anastomotic leakage being the most frequent cause (3.55%). There was no statistically significant difference in the presence of sepsis among patients when gender, surgical approach, duration of surgery, and respiratory disease were taken into account. Sixty-nine patients were > 65 years old, with sepsis being statistically significant in this group (p = 0.034). Furthermore, patients with ASA class ≤ 2 developed postoperative sepsis less frequently than patients with advanced ASA scores (p = 0.008). Diabetes and cardiovascular disease also reach statistical significance; sepsis was more frequent in this group of patients (p = 0.013 and p = 0.009, respectively). Conclusions: Following colorectal cancer procedures, postoperative sepsis was significantly more common among patients over 65 years old, ASA score > 2, and also with associated comorbidities such as diabetes and cardiovascular disease.

The impact of osteoporosis and vertebral compression fractures on mortality and association with pulmonary function in COPD: A meta-analysis.

OBJECTIVE: Osteoporosis is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and most commonly presents as a vertebral compression fracture (VCF). Our objective was to quantify the effect of osteoporosis and VCFs on the mortality and pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), of patients with COPD. METHODS: A PubMed/Medline search was conducted using the search terms "chronic obstructive pulmonary disease", "osteoporosis" and "vertebral compression fracture". Meta-analyses were conducted to evaluate the differences in mortality and PFTs between patients with COPD with and without osteoporosis or VCFs, according to PRISMA guidelines. PROSPERO registration: CRD42019120335. RESULTS: Of the 896 abstracts identified, 27 studies describing 7662 patients with COPD of which 1883 (24.6%) had osteoporosis or VCFs, were included. Random effects model analysis demonstrated that patients with COPD and osteoporosis or VCFs had an increased OR for mortality of 2.40 (95% CI: 1.24; 4.64, I2=89%, P<0.01), decreased FEV1/FVC with a mean difference of -4.80% (95% CI: -6.69; -2.90, I2=83%, P<0.01) and decreased FEV1, with a mean difference of -4.91% (95% CI: -6.51; -3.31, I2=95%, P<0.01) and -0.41 L (95% CI: -0.59; -0.24, I2=97%, P<0.01), compared to control subjects. Apart from FEV1 (liters) in subgroup 1 (P=0.06), all subgroup analyses found significant differences between groups, as did sensitivity analysis of low risk of bias studies. CONCLUSION: Osteoporosis and VCFs are associated with a significant reduction in survival and pulmonary function among patients with COPD.

Mechanisms of Antibiotic Resistance in Important Gram-Positive and Gram-Negative Pathogens and Novel Antibiotic Solutions.

Multidrug-resistant bacteria have on overwhelming impact on human health, as they cause over 670,000 infections and 33,000 deaths annually in the European Union alone. Of these, the vast majority of infections and deaths are caused by only a handful of species-multi-drug resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp. and Klebsiella pneumoniae. These pathogens employ a multitude of antibiotic resistance mechanisms, such as the production of antibiotic deactivating enzymes, changes in antibiotic targets, or a reduction of intracellular antibiotic concentration, which render them insusceptible to multiple antibiotics. The purpose of this review is to summarize in a clinical manner the resistance mechanisms of each of these 6 pathogens, as well as the mechanisms of recently developed antibiotics designed to overcome them. Through a basic understanding of the mechanisms of antibiotic resistance, the clinician can better comprehend and predict resistance patterns even to antibiotics not reported on the antibiogram and can subsequently select the most appropriate antibiotic for the pathogen in question.

Risk of surgical site infections after colorectal surgery and the most frequent pathogens isolated: a prospective single-centre observational study.

Aim To identify risk factors for developing surgical site infections (SSIs) based on a prospective study of patients undergoing colorectal surgery. Methods Between November 2019 and January 2021, 133 patients underwent elective operation for colorectal cancer in our institution. The following variables were recorded for each patient: age, gender, body mass index (BMI), American Society of Anesthesiologists Classification (ASA class), duration of surgery, wound classification, skin preparation regimens, surgical approach, comorbidities (hypertension, diabetes, cardiovascular disease, respiratory disease, chronic steroid use), and pathogens responsible for surgical site infection. Univariate analysis was performed using χ2 tests for categorical variables. Results A total of 65 males and 68 females were enrolled. Postoperative SSI was diagnosed in 29 (21.8%) cases. Fifty five patients were >70 years old, and SSIs were significantly more frequent in this group (p=0.033). There were 92 patients with BMI <30kg/m2 and 87 with ASA class ≤2; SSIs occurred significantly less frequently in these patients (p=0.021 and p=0.028, respectively). Open surgery was performed in 113 patients; 35 (out of 113; 31%) wound infections were classified as contaminated or dirty, and SSI occurred more often in these two groups (p=0.048 and p=0.037, respectively). Nineteen patients had diabetes and 36 used steroids continuously; SSI was significantly more frequent in these patients (p=0.021 and p=0.049, respectively). Conclusion Following colorectal cancer procedures SSIs were significantly more common among patients over 70 years old, BMI≥30kg/m2 , ASA score>2, with diabetes and chronic steroid use, undergoing open, dirty or contaminated surgery. Escherichia coli and Enterococcus spp. were the two most common pathogens isolated.

A Prototype of the National EHR system for Cyprus.

The aim of this paper is to present Cyprus' initiative for the design and the implementation of the prototype of the integrated electronic health record at a national level that will establish the foundations of the country's broader eHealth ecosystem. The latter, requires an interdisciplinary approach and scientific collaboration among various fields, including medicine, information and communication technologies, management, and finance, among others. The objective, is to design the system architecture, specify the requirements in terms of clinical content as well as the hardware infrastructure, but also implement European and national legislation with respect to privacy and security that govern sensitive medical data manipulation. The present study summarizes the outcomes of the 1st phase of this initiative, which comprises of the healthcare as well as the administrative requirements, user stories, data-flows and associated functionality. Moreover, leveraging the HL7 Fast Healthcare Interoperability Resources (FHIR) standard we highlight the concluded interoperability framework that allows genuine cross-system communication and defines third-party systems connectivity.Clinical Relevance- This work is strongly correlated with medicine since it describes the system requirements and the architecture of a national integrated electronic health records system.

A meta-analysis of transient elastography for the detection of hepatic fibrosis.

OBJECTIVES: The use of transient elastography to assess liver stiffness measurement (LSM) has now become widely available for the diagnosis of liver fibrosis as a rapid, noninvasive test (it is still not approved for use in the United States). It has previously been showed as an accurate method of representing the state of liver fibrosis with concomitant evaluation of liver biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to further assess its use in comparison with liver biopsy. METHODS: Studies from the literature were analyzed with a median liver stiffness value in kilopascal given for fibrosis stages according to histopathologic findings on biopsy and best discriminant cutoff levels in kilopascals for significant fibrosis (>or=F2) and cirrhosis (F4). RESULTS: A total of 22 studies were selected comprising 4,430 patients; chronic hepatitis C infection was the most common etiology of fibrosis. The pooled estimates for significant fibrosis (>or=F2) measured 7.71 kPa (LSM cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%-72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4) the results showed a cutoff of 15.08 kPa with a sensitivity of 84.45% (95% CI: 84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). CONCLUSIONS: Further evaluation of transient elastography to assess LSM is required in prospective studies to potentially increase the sensitivity and establish its clinical utility.

Behçet's disease presenting as recurrent oral aphthosis in a 9-year-old boy from Greece.

We report a case of Behçet's disease in a 9-year-old boy from Greece, presenting with a history of recurrent ulceration of the oral cavity. Following inspection of the oral cavity, which revealed lesions on both the upper and lower labial mucosa, as well as a large ulcer on the apex of the tongue, the diagnosis of Behçet's disease was immediately suspected. The diagnosis was confirmed using the International Criteria for Behçet's Disease. Nevertheless, as multiple diseases can cause recurrent oral aphthosis, an extensive differential diagnosis was made, and pertinent tests were undertaken to exclude other causes of oral ulceration. The approach to a patient with Behçet's disease, as well as its various clinical presentations and complications, is discussed.

Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge.

Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50-66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.

Antimicrobial Properties on Non-Antibiotic Drugs in the Era of Increased Bacterial Resistance.

In recent years, due to the dramatic increase in and global spread of bacterial resistance to a number of commonly used antibacterial agents, many studies have been directed at investigating drugs whose primary therapeutic purpose is not antimicrobial action. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, it is important to understand these antimicrobial effects and their potential clinical implications. Numerous studies report the antibacterial activity of non-steroidal anti-inflammatory drugs, local anaesthetics, phenothiazines such as chlorpromazine, levomepromazine, promethazine, trifluoperazine, methdilazine and thioridazine, antidepressants, antiplatelets and statins. Several studies have explored a possible protective effect of statins inreducing the morbidity and mortality of many infectious diseases. Various non-antibiotic agents exhibit antimicrobial activity via multiple and different mechanisms of action. Further studies are required in the field to further investigate these antimicrobial properties in different populations. This is of paramount importance in the antimicrobial resistance era, where clinicians have limited therapeutic options to combat problematic infections.