Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1.5. The lack of specificity and ability to distinguish acute liver failure from previous liver dysfunction disqualifies bilirubin as a single parameter reflecting the complex liver function. Clinical manifestations of sepsis-associated liver dysfunction include hypoxic hepatitis, sepsis-induced cholestasis and dysfunction of protein synthesis manifesting with, e.g., coagulopathies. Detoxifying liver dysfunction, which is associated with an increase in serum ammonia concentration, manifesting with e.g., confusion, loss of consciousness and hepatic encephalopathy, may be disguised by analgosedation used in the intensive care unit. To determine a liver dysfunction in a critically ill patient, the concept of shock liver may be used. It is a complex syndrome of hemodynamic, cellular, molecular and immunologic changes leading to severe liver hypoxia. In clinical practice, there is no standardized diagnostic panel that would allow for an early, clear diagnosis of acute liver dysfunction, and there is no therapeutic panel enabling the full restoration of damaged liver function. The aim of the article is to present the pathophysiology and clinical manifestations of sepsis-associated liver dysfunction.

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HPV infections are currently the most frequent cause of genital infections in the USa. Risk factors are early onset of sexual activity, multiple sexual partners, a history STds, an early age of first pregnancy and tobacco use. In the past, HPV viruses were thought to be STds, but it is now known that penetration is not necessary. Skin-to--skin or mucosa-to-mucosa contact is enough to transmit the virus, which presents high tropism for those tissues. The Papillomaviridae family includes over 120 viruses, some of which have high malignant transformation rates. The most common malignancy connected to HPV is uterine cervix cancer and anal canal cancer. The range of morphology of perianal lesions means that a thorough clinical examination is required, including an anoscopy. Therapeutic modalities often seek to eliminate macroscopic changes rather than focus on the cause of the infection, which leads to a high recurrence rate. Externally located changes can be eliminated with patient-applied treatments. Those located in the anal canal and distal end of the rectal ampulla require treatment by a qualified medical provider. due to the high recurrence rate after standard treatment, special attention has been given to vaccinations. The polyvalent vaccine includes HPV viruses with both low and high malignant transformation risk. This has led to a decrease in the rate of malignancies (Adv Clin Exp Med 2014, 23, 2, 307-311). The Epidemiology and Biology of HPV Anal InfectionsThe Human Papilloma Virus (HPV) used to be thought of as one of the most common sexually transmitted diseases (STds) [1]. However, penetrative sexual contact is not in fact necessary to transmit the virus, which is predominantly transmitted by skin-to-skin or mucosa-to-mucosa contact [2]. The HPV family (Papillomaviridae) consists of more than 120 viruses presenting a tropism towards either the cutaneous or mucosa epithelium. The frequency of HPV infection has risen in the past 35 years, and this can be attributed to a decrease in the age of the first sexual contact as well as an increase in the number of sex partners [3]. HPV is the most common genital infection in the US, and the lifetime risk of at least one HPV infection in women is 75% [1,4]. The prevalence of anal HPV infection is very high: about 57% in HIV-negative men who have sex with men (MSM) [5]; and among HIV-positive men the infection rate is about 60 times higher than in the general male population [6]. Several risk factors for HPV infection have been identified: early onset of sexual activity, multiple sexual partners, a history of STds, an early age of first pregnancy and tobacco use [7].HPV penetrates skin or mucosa up to the basal membrane in search of keratinocytes (basal

Inasmuch as polymorphonuclear leukocytes (PMNs) play a major role in antibacterial defense but can also cause substantial tissue injury, drugs are needed which are able to attenuate tissue-toxic PMN reactions without inhibiting bactericidal mechanisms. Adenosine as a retaliatory metabolite is produced in response to metabolically unfavorable conditions like inflammation. However, it is not known whether adenosine can selectively downregulate adverse PMN reactions in sepsis. In this prospective clinical study, we characterized the effects of adenosine ex vivo on PMN functions in patients with septic shock ([SS] n = 33) and healthy volunteers ([HV] n = 33). The PMNs were primed by tumor necrosis factor-alpha (TNF-alpha) and subsequently stimulated with N-formyl methionyl-leucyl-phenylalanine (fMLP) to test for the formation of hydrogen peroxide (H2O2) in response to soluble inflammatory stimuli. The PMNs were also challenged by opsonized zymosan particles to assess adhesion, phagocytosis, and the associated H2O2 production. As compared with HV, PMNs from SS patients showed strongly enhanced tissue-toxic H2O2 production elicited by TNF-alpha/fMLP. Increasing concentrations of adenosine dose-dependently reduced this tissue-toxic H2O2 production in both groups with a half-maximal inhibitory concentration of 25 nmol/L and 114 nmol/L in HV and SS patients, respectively. This 4.6-fold decrease in the adenosine-mediated inhibition of PMNs from patients with septic shock was compensated by a 3-fold increase in the plasma concentrations of the nucleoside (HV, 42.5 +/- 2.9 nmol/L vs. SS, 125.6 +/- 18.2 nmol/L; mean +/- SEM). When the effects of adenosine were tested at a very high A2A receptor saturating concentration of 10 mol/L, neither adhesion, phagocytosis, nor the associated H2O2 production induced by opsonized zymosan was affected in both groups. These results were confirmed by the highly selective A2A agonist, CGS21680.Thus, adenosine or A2A agonists may be useful to selectively inhibit the potentially tissue-toxic H2O2 production elicited by soluble inflammatory mediators in patients with septic shock.

Human papillomavirus (HPV) is a virus often infecting humans. It is often present on skin or mucous membranes. These diverse DNA viruses are often linked to many various benign and malignant neoplastic lesions. Over 40 types of HPV are transmitted through sexual contact and infect the anogenital region which might be secondly transmitted to the oral mucous. Over 150 HPV viruses are defined according to the invaded site. Oral papillomas are marked with numbers 6, 7, 11, 16 and 32. Squamous cell papilloma is often found in laryngeal epithelial tumor associated with HPV-6 and HPV-11 and also HPV-16 in oral squamous cell carcinoma (OSCC). In the last 15 years OSCC has become more common in children and young adults. The role of HPV virus causing oral squamous cell carcinomas is more often realized, but people's lack of knowledge and risky sexual behavior is still the main factor in growing HPV infections.