Changes in hair cortisol levels and cognitive function among older patients in palliative care.

This monocentric pilot study aimed to assess whether there are significant changes in hair cortisol levels and cognitive functioning at baseline and after 3 weeks of hospitalisation in older palliative care patients, and to ascertain whether hair cortisol can be used as a pertinent stress biomarker in this population. Hair cortisol concentration levels were measured with the use of an enzyme-linked immunosorbent assay (ELISA), while cognitive functions were assessed by using 16-point Mini-Mental State Examination 2 (MMSE-2): brief version. A statistically significant difference in mean hair cortisol levels at the start of the hospitalisation was found when compared to the 3-week follow-up (p=0.007). No statistically significant differences were observed regarding MMSE-2 scores using the same time points. These results have direct clinical implications and set the stage for further research endeavours in the field.

A Putative Role of Candida albicans in Promoting Cancer Development: A Current State of Evidence and Proposed Mechanisms.

Candida albicans is a commensal fungal species that commonly colonizes the human body, but it is also a pervasive opportunistic pathogen in patients with malignant diseases. A growing body of evidence suggests that this fungus is not only coincidental in oncology patients, but may also play an active role in the development of cancer. More specifically, several studies have investigated the potential association between C. albicans and various types of cancer, including oral, esophageal, and colorectal cancer, with a possible role of this species in skin cancer as well. The proposed mechanisms include the production of carcinogenic metabolites, modulation of the immune response, changes in cell morphology, microbiome alterations, biofilm production, the activation of oncogenic signaling pathways, and the induction of chronic inflammation. These mechanisms may act together or independently to promote cancer development. Although more research is needed to fully grasp the potential role of C. albicans in carcinogenesis, the available evidence suggests that this species may be an active contributor and underscores the importance of considering the impact of the human microbiome on cancer pathogenesis. In this narrative review, we aimed to summarize the current state of evidence and offer some insights into proposed mechanisms.

Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review.

Both diabetes and fungal infections contribute significantly to the global disease burden, with increasing trends seen in most developed and developing countries during recent decades. This is reflected in urogenital infections caused by Candida species that are becoming ever more pervasive in diabetic patients, particularly those that present with unsatisfactory glycemic control. In addition, a relatively new group of anti-hyperglycemic drugs, known as sodium glucose cotransporter 2 inhibitors, has been linked with an increased risk for colonization of the urogenital region with Candida spp., which can subsequently lead to an infectious process. In this review paper, we have highlighted notable virulence factors of Candida species (with an emphasis on Candida albicans) and shown how the interplay of many pathophysiological factors can give rise to vulvovaginal candidiasis, potentially complicated with recurrences and dire pregnancy outcomes. We have also addressed an increased risk of candiduria and urinary tract infections caused by species of Candida in females and males with diabetes, further highlighting possible complications such as emphysematous cystitis as well as the risk for the development of balanitis and balanoposthitis in (primarily uncircumcised) males. With a steadily increasing global burden of diabetes, urogenital mycotic infections will undoubtedly become more prevalent in the future; hence, there is a need for an evidence-based approach from both clinical and public health perspectives.

The role of magnetic resonance imaging and the expression of MMP-9 protein in the analysis of carotid atherosclerotic plaques in patients undergoing carotid endarterectomy: a prospective pilot study.

Components of carotid atherosclerotic plaque can be analysed preoperatively by non-invasive advanced imaging modalities such as magnetic resonance imaging (MRI). The expression of matrix metalloproteinase-9 protein (MMP-9), which has a potential role in remodelling of atherosclerotic plaques, can be analysed immunohistochemically. The aim of the present prospective pilot study is to analyse histological characteristics and expression of MMP-9 in carotid plaques of patients undergoing carotid endarterectomy (CEA) and to investigate the correlation with preoperative clinical symptoms and MRI features. Preoperative clinical assessment, MRI imaging, postoperative histological and immunohistochemical analyses were performed. Fifteen patients with symptomatic (7/15; 47%) and asymptomatic carotid artery stenosis undergoing CEA were included. Among symptomatic patients, 5 (71%) had recent stroke and 2 (29%) had recent transient ischaemic attack with a median timing of 6 weeks (IQR: 1, 18) before the surgery. Both groups did not significantly differ in respect to preoperative characteristics. Prevalence of unstable plaque was higher in symptomatic than asymptomatic patients, although it was not significant (63% vs. 37%, p = 0.077). The expression of MMP-9 in CD68 cells within the plaque by semiquantitative analysis was found to be significantly higher in symptomatic as compared to asymptomatic patients (86% vs. 25% with the highest expression, p = 0.014). The average microvascular density was found to be higher and lipid core area larger among both symptomatic patients and unstable carotid plaque specimens, although this did not reach statistical significance (p = 0.064 and p = 0.132, p = 0.360 and p = 0.569, respectively). Our results demonstrate that MRI is reliable in classifying carotid lesions and differentiating unstable from stable plaques. We have also shown that the expression of MMP-9 is significantly higher among symptomatic patients undergoing CEA.

Topical medication as an initial therapeutic option for protruding and non-protruding condylomata acuminata of the distal urethra.

Genital warts (also known as condylomata acuminata) caused by the human papillomavirus (HPV) represent one of the most common sexually transmitted infections. Although they are usually found in the outer genital region, a small proportion of men can present with (often unrecognised) intraurethral warts, generally limited to the distal urethra and urethral meatus. This poses a treatment challenge not adequately addressed by the current guidelines. Here, we present two cases of low-risk HPV-positive patients with protruding and non-protruding condylomata acuminata of the distal urethra, which were treated successfully by using two different topical regimens (ie, a combination of policresulen and imiquimod for one patient and 5-fluorouracil monotherapy for the other). Although this type of management results in lower rates of tissue destruction and complications and may be given preference as an initial therapeutic option, additional prospective comparative clinical studies are needed to elucidate its potential in similar cases.

Seasonal Coronaviruses and Other Neglected Respiratory Viruses: A Global Perspective and a Local Snapshot.

Respiratory viral infections are the leading cause of morbidity and mortality in the world; however, there are several groups of viruses that are insufficiently routinely sought for, and can thus be considered neglected from a diagnostic and clinical standpoint. Timely detection of seasonality of certain respiratory viruses (e.g., enveloped viruses such as seasonal coronaviruses) in the local context can aid substantially in targeted and cost-effective utilization of viral diagnostic approaches. For the other, non-enveloped and year-round viruses (i.e., rhinovirus, adenovirus, and bocavirus), a continuous virological diagnosis needs to be implemented in clinical laboratories to more effectively address the aetiology of respiratory infections, and assess the overall impact of these viruses on disease burden. While the coronavirus disease 2019 (COVID-19) pandemic is still actively unfolding, we aimed to emphasize the persistent role of seasonal coronaviruses, rhinoviruses, adenoviruses and bocaviruses in the aetiology of respiratory infections. Consequently, this paper concentrates on the burden and epidemiological trends of aforementioned viral groups on a global level, but also provides a snapshot of their prevalence patterns in Croatia in order to underscore the potential implications of viral seasonality. An overall global prevalence in respiratory tract infections was found to be between 0.5 and 18.4% for seasonal coronaviruses, between 13 and 59% for rhinoviruses, between 1 and 36% for human adenoviruses, and between 1 and 56.8% for human bocaviruses. A Croatian dataset on patients with respiratory tract infection and younger than 18 years of age has revealed a fairly high prevalence of rhinoviruses (33.4%), with much lower prevalence of adenoviruses (15.6%), seasonal coronaviruses (7.1%), and bocaviruses (5.3%). These insights represent a relevant discussion point in the context of the COVID-19 pandemic where the testing of non-SARS-CoV-2 viruses has been limited in many settings, making the monitoring of disease burden associated with other respiratory viruses rather difficult.

Inferior pancreaticoduodenal artery aneurysms and Dunbar syndrome. Experience with the open surgery.

INTRODUCTION: Median arcuate ligament or Dunbar syndrome is a rare vascular disorder causing celiac trunk stenosis or occlusion due to the extrinsic compression by the median arcuate ligament. A visceral aneurysm may develop as a complication. PATIENTS AND METHODS: We experienced an inferior pancreaticoduodenal artery aneurysm presentation in two female patients with the median arcuate syndrome previously diagnosed. One patient presented with postprandial abdominal pain and weight loss and the other one was asymptomatic. RESULTS: We described our experience with the both patients being successfully treated surgically. CONCLUSIONS: Awareness of possible repercussions of the celiac trunk stenosis to peripancreatic arteries should be elevated. Restoration of physiological blood flow by removing pathologic anatomy should be performed. Since there is no correlation between the size of a visceral aneurysm and the risk of rupture, having a high postrupture mortality, pancreaticoduodenal artery aneurysms should be treated even if asymptomatic. Surgical treatment remains the mainstay treatment of the Dunbar syndrome complicated by visceral aneurysms.

Human Papillomavirus (HPV) Prevalence, Temporal Dynamics and Association with Abnormal Cervical Cytology Findings in Women from Croatia: Is there a Compounding Effect of Low-Risk/High-Risk HPV Co-Infection?

BACKGROUND: Human papillomavirus (HPV) is a major risk factor for cervical dysplasia and invasive cervical cancer; therefore, regular screening by cervical smear cytology or HPV testing is recommended. We aimed to determine the overall and risk group-specific HPV prevalence, age distribution, and temporal trends and to appraise the correlation of HPV positivity with abnormal cervical cytological findings. METHODS: This retrospective, single-center study involved a total of 751 women (aged 18 - 67) concurrently subjected to HPV DNA testing and cervical cytology evaluation over a 10-year period in Zagreb, Croatia. Digene HC2 HPV DNA test (Qiagen Corporation, USA) was employed in screening specimens for both low-risk and high-risk HPV risk groups. The cytology was reported using the Bethesda system and in accordance with uniform classification of uterine cervix cytological findings in Croatia "Zagreb 2002". Statistical significance was set at p < 0.05. RESULTS: The overall HPV prevalence in our study population was 48.6%, and the 18 - 30 age group presented with the highest infection burden (p = 0.046). A decrease in low-risk and high-risk mono-positivity has been observed over the 10-year period; conversely, there was a significant increase in low-risk/high-risk co-positivity (p = 0.007). Low-risk/high-risk HPV co-infection resulted in a compounding effect which increased the occurrence of abnormal cells, HPV-associated changes and low grade squamous intraepithelial lesions (LSIL/cervical intraepithelial neoplasia grade I) in cervical cytology when compared to mono-infection with either low-risk or high-risk HPV. On the other hand, such effect has not been demonstrated for high grade squamous intraepithelial lesions (HSIL/ cervical intraepithelial neoplasia grades II and III). CONCLUSIONS: The overall HPV prevalence in female outpatients was high, underscored with rising co-positivity rates. Such co-infection with both low-risk and high-risk HPV (predominantly seen in women younger than 30) can exhibit a compounding effect in the occurrence of cytological abnormalities and low grade squamous intra-epithelial lesions (LSIL), which has to be considered in future diagnostic and screening algorithms.

Recurrent Aortic Infections Due to Unrecognized Aorto-Enteric Fistula.

We report a case of an infrarenal abdominal aortic aneurysm (AAA) with unrecognized primary aortoduodenal fistula (ADF), treated by endovascular aortic repair (EVAR). Endograft infection was diagnosed 12 months thereafter. The associated ADF was uncovered during open surgery, which included endograft extraction, in situ aortic reconstruction with a cryopreserved homograft (CHG) and duodenal repair. The patient was urgently reoperated in the early postoperative course, due to CHG rupture and subsequent hemorrhagic shock. After establishing control of hemorrhage, CHG was explanted, followed by aortic ligation and extraanatomical reconstruction with axillofemoral bypass. The importance of timely diagnosis of primary ADF prior to AAA repair, as well as treatment options and optimal materials for simultaneous aortic and bowel reconstruction in the setting of primary or secondary ADF, are discussed.

Proposed dual antagonist approach for the prevention and treatment of urinary tract infections caused by uropathogenic Escherichia coli.

Urinary tract infections are among the most common infectious diseases worldwide, primarily caused by uropathogenic Escherichia coli (UPEC) strains that harbor type I pili and P pili on the surface. Standard E. coli therapy still entails antibiotic consumption, but urinary tract infections tend to recur at a very high rate. Due to the emergence of antibiotic resistant strains of UPEC, as well as high infection recurrence rates, there is a need for new approaches to efficiently treat and prevent urinary tract infections. Since aforementioned adhesive organelles are the principal virulence factors in UPEC, anti-adhesion strategy seems to be the most promising (and hitherto unexplored) treatment option. Here we propose an antiadhesive dual targeting approach towards FimH and PapG adhesive proteins placed on two key virulence factors for UPEC - type I fimbriae and P pili. Such dual antagonists will contain appropriate pharmacophores (mannose and natural cranberry-containing polyphenol) joined together and will more efficiently block the infection and prevent the progression of the disease in comparison to FimH and PapG as isolated targets. More specifically, polyphenol mannosides (due to the structural similarities with the most potent biaryl inhibitors) can act as high-affinity FimH ligands, while cranberry-associated polyphenol moiety can additionally inhibit the PapG-mediated adhesion. Proposed compound may also contribute to the antioxidant capacity of the human organism. In conclusion, this dual-target hypothesis for the prevention and treatment of UPEC infections represents an important foundation for further research on this topic.

High Detection Rates of Human Bocavirus in Infants and Small Children with Lower Respiratory Tract Infection from Croatia.

BACKGROUND: Human bocavirus (HBoV) is known to cause lower respiratory tract infections (LRTI) in children and may result in substantial morbidity and mortality. The aim of this study was to determine HBoV prevalence among hospitalized infants and small children with acute LRTI in Zagreb, Croatia, as well as to evaluate HBoV DNA quantity in samples in relation to the patients' age and co-infection with other respiratory viruses. METHODS: During winter season 2016/2017, a total of 295 children younger than three years of age who were admitted to hospitals with LRTI were tested for the presence of HBoV, respiratory syncytial virus (RSV), adenovirus (ADV), parainfluenza virus (PIV) types 1 to 3, and human metapneumovirus (HMPV). HBoV was detected with a real-time PCR method, and the other viruses were diagnosed using monoclonal antibodies in direct fluorescence assay. RESULTS: Viral etiology was proven in 225/295 (76.3%) of patients. The most commonly diagnosed virus was RSV (59.3%), followed by HBoV (23.1%), PIVs (4.4%), ADV (3.1%), and HMPV (1.4%). HBoV-infected children were older than RSV-infected children; likewise, detection rates of HBoV infection increased with age, while RSV infection rates decreased with age. In 51% of HBoV-positive samples an additional respiratory virus was also detected. There was no difference in HBoV DNA quantity between samples with single virus detection and those with multiple virus detection (p = 0.056), although samples positive only for HBoV showed higher cycle threshold values. There was no difference in HBoV DNA quantity in samples of different age groups (p > 0.05). CONCLUSIONS: Frequent detection of HBoV in small children with LRTI, even in combination with other viruses, highlights its role in the pathogenesis of respiratory disease.

Endovascular Treatment of a Late False Aneurysm Complicating Open Suprarenal Mycotic Aneurysm Repair with a Cryopreserved Aortic Homograft.

We report a patient who was initially treated for a suprarenal mycotic aortic aneurysm. The aneurysm repair was performed using a cryopreserved arterial homograft and debranching of visceral arteries. Five years later, the patient was referred due to a large symptomatic false aneurysm at the distal homograft anastomosis. Endovascular repair was indicated and performed using a bifurcated Medtronic composite stent graft. The procedure was uneventful, while control angiography showed complete exclusion of the false aneurysm. Within 6 months of follow-up, the endograft showed favorable position and maintained patency with no signs of endoleaks. We discuss the role of the cryopreserved homografts for in situ repair of mycotic aortic aneurysms and comment on possible late complications after placing those grafts.

Effective anti-adhesives of uropathogenic Escherichia coli.

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are among the most common infectious diseases in humans. Due to their frequent occurrence in the community and nosocomial settings, as well as the development of resistance to the commonly prescribed antimicrobial agents, an enormous financial burden is placed on healthcare systems around the world. Therefore, novel approaches to the prevention and treatment of UTIs are needed. Although UPEC may harbour a plethora of virulence factors, type I fimbriae and P pili are two of the most studied adhesive organelles, since the attachment to host cells in the urinary tract is a crucial step towards infection. Design of receptor analogues that competitively bind to UPEC surface adhesins placed at the top of pili organelles led to the development of anti-adhesive drugs that are increasingly recognized as important and promising alternatives to antibiotic treatment of UTIs.

The role of occupational medicine in assessing work limitation: A cross-sectional study on construction workers over a five-year period in Croatia.

BACKGROUND: Maintaining adequate working ability of construction workers is of considerable importance for society, as the construction sector is burdened with high prevalence of work-related diseases and health-issues. OBJECTIVE: To determine the number and age of construction workers in Croatia with temporary or permanent work limitation status, as well as to identify the most common health causes of such work limitation. METHODS: A retrospective cross-sectional study was performed using the data from 2534 construction workers, aged between 18 and 65 years, who underwent standardized routine occupational health examinations between 2011 and 2015. Thorough medical history and medical record reviews, blood and urine analyses, vision parameters and hearing range evaluation, as well as mental health assessment were conducted on every study participant. RESULTS: A total of 210 construction workers (8.29%) received occupational/work limitation status (either temporary or permanent). Four main categories of work limitation were high blood pressure, disorders of the liver and digestive system, hearing loss and amblyopia, comprising 61.69% of all diagnoses. A total of 37.62% of workers with work limitation status had two or more different diagnoses (i.e. co-morbid conditions). Those with work limitation (either temporary or long-term) were significantly older than those fit enough to work (p-value <0.00001). CONCLUSIONS: This type of organized screening represents a significant preventative effort in the construction industry, as workers may become more cognizant of the conditions that may affect their work ability.

Characteristics and Distribution of Penile Lesions in Croatian Men with Laboratory-Confirmed Low-Risk and High-Risk Human Papillomavirus (HPV) Infection.

BACKGROUND: Studies that compare penoscopic evaluation with the results of molecular human papillomavirus (HPV) testing are scarce. This study assessed and compared both type and distribution of various penile lesions using penoscopy (peniscopy) technique in Croatian men with different, laboratory-confirmed HPV status. METHODS: From a large cohort of men attending an outpatient STD clinic for HPV testing, a total of 120 patients were randomly selected and grouped into those positive for low-risk HPV, high-risk HPV, both low-risk and highrisk HPV, and those with negative results. Samples for HPV-DNA detection were taken by penile brushing and tested with the hc2 HPV DNA Test using Hybrid Capture 2 technology. Lesions were observed by photocolposcope after the application of aqueous 5% acetic acid, and classified as flat (macular), papular, papillary, classical condyloma, PIN-suspicious and non-specific lesions. RESULTS: The results have shown that flat and non-specific acetowhite lesions were the most common overall. All groups differed significantly with respect to papular and papillary lesions. A combination of heterogeneous lesions (i.e., a mixed penoscopic pattern) was commonly observed in all HPV-positive groups, but was significantly lower in the HPV-negative group. A majority of lesions were located in the coronal sulcus, and the four groups differed with respect to the location only considering the lesions of the penile shaft. Distribution of lesions in different sites did not appear to be significantly different with respect to the group, although differences within the high-risk HPV group and the group with both low-risk and high-risk HPV were detected. CONCLUSIONS: Penoscopy is relevant, but not a conclusive diagnostic tool for differentiating HPV from non-HPV findings in men - thus combining it with an HPV DNA test represents a more reliable approach.