Monkeypox in humans – the review

Monkeypox is an emerging zoonotic disease caused by the monkeypox virus with a presentation similar to smallpox. Being previously endemic to Africa, now the disease is spreading across the world, causing fear of a potential next pandemic. Smallpox vaccine, previously providing cross-immunity to monkeypox virus, due to cessation of vaccinations, caused the decline in immunity against these viruses. Defined ways of transmission are animal-to-human through consumption or attack by an affected animal, human-to-human through close contact, or via respiratory droplets. Currently, there are no specific antiviral drugs and vaccine specific to monkeypox, and for symptomatic care, there are no determined guidelines

Primary Membranous Nephropathy - what do we know today?

Introduction: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults, characterized by the deposition of immune complexes in the glomerular basement membrane. Aim of this study: evaluate the features of PMN such as incidence, pathology, clinical features and assess the effectiveness of immunosuppressive therapy. Materials and Methods: The review was based on articles found in PubMed database, using keyword „primary membranous nephropathy” with appropriate sufixes. Results: PMN is a challenging disease that requires a multidisciplinary approach to diagnosis and management. Laboratory tests, including assessment of autoantibodies and complement levels, are essential for the diagnosis of PMN. Immunosuppressive therapy can be effective in inducing remission in a significant proportion of patients. Conclusions: Further research is needed to optimize the duration and intensity of immunosuppressive therapy, and to evaluate the role of newer therapies such as rituximab and belimumab

New Opportunities and Challenges for Health Professionals in the era of Artificial Intelligence – Review

Introduction and purpose: Modern medical knowledge has grown to a vastness incomprehensible for a single health professional to learn and accommodate. The usage of modern information technologies comes to help, one of them being artificial intelligence, a branch of computer science aimed at developing solutions to perform tasks similar to the human brain, but more efficient and complex, without actual human intervention.  The goal of this review is to provide reader with the knowledge how artificial intelligence is applied in various branches of medicine. Brief description of the state of knowledge: In the fields of infectious diseases, including COVID-19 diagnostics, radiology, dermatology and surgery, works lean toward the statement, which suspect application of AI is beneficial for medical practitioners. Programs help to develop statistical models for virus spreading and the creation of antiviral solutions. The radiological application involves the analysis of images to aid radiologists in diagnosing certain features, similarly to dermatology, where eg. AI can identify malignancy of skin nevi. In the department of surgery, predictive algorithms can help in choosing operation methods and improve outcomes. Conclusions: Usage of AI assistance in the medical field has proven to be successful, but it is yet to be commonly encountered in everyday work. Programs need to be further developed and made more approachable to users without expertise in the IT field. AI may also prove useful in the process of education of health professionals

Dual therapy based on raltegravir and boosted protease inhibitors : the experience of Polish centers

Introduction: The aim of the study was to present the experience of Polish centers regarding dual therapy based on the integrase inhibitor raltegravir (RAL) and ritonavir-boosted protease inhibitors (PI/r) for treating treatment-naïve and -experienced HIV-infected patients. Material and methods: The paper concerns a retrospective multicenter study. The medical databases of six main Polish HIV centers from January 2009 to December 2014 were analyzed for the use of combined antiretroviral treatment consisting of RAL + PI/r. This study included 126 HIV-infected patients receiving RAL + PI/r therapy, of whom 17 patients were treatment-naive and 109 patients were treatment-experienced. Results: In treatment-experienced patients, the most common reasons for the introduction of a RAL + PI/r regimen were virologic failure and impaired renal function (45 of 109 patients). In the treatment-naïve group kidney disease was the cause of the RAL + PI/r regimen in 3 of 17 participants. In treatment-experienced patients, 80% of individuals still were on RAL + PI/r treatment after 12 months, 65% after 24 months and 53% of subjects after 60 months. In both groups, the simplification of the antiretroviral regimen was the most common reason for discontinuation of RAL + PI/r based therapy. Conclusions: In antiretroviral-experienced patients the dual therapy based on RAL + PI/s is safe and effective. In antiretroviral-naïve patients the RAL + PI/r regimen is rarely used in Poland

Real-life study of dual therapy based on dolutegravir and ritonavir-boosted darunavir in HIV-1-infected treatment-experienced patients

<div><p>Background</p><p>Dual therapy based on dolutegravir and ritonavir-boosted darunavir (DTG/DRV/r) is a combination of well-known drugs with a high genetic barrier to HIV resistance.</p><p>Method</p><p>A retrospective analysis of all HIV-1 infected treatment-experienced patients who switched to DTG/DRV/r from May 2014 till March 2017 in 4 Polish centres–results of a 48-week treatment.</p><p>Results</p><p>The study group consisted of 59 men and 17 women. Median baseline parameters were: age– 42.7 years, CD4 cells count– 560.5 cells/μl, CD4 cells nadir– 150 cells/μl, <i>number</i> of prior antiretroviral <i>regimens–</i> 3. The introduction of dual therapy was primarily due to virologic failure (30 patients), adverse events on previous regimens (17 patients) and therapy simplification (27 patients). At week 48 the treatment <i>was continued</i> in 70/76 of patients and the median CD4 cells count increased from 560.5 to 641.0 cells/μl. The therapy was discontinued in six patients (1 –virologic failure, 1 –decrease of estimated glomerular filtration rate (eGFR), 1 –myalgia, 3 –lost to follow-up). At week 48 six patients had detectable viremia, but only in one patient viremia was higher than 200 copies/ml. At week 48 the level of serum total cholesterol of the investigated subjects was statistically significantly higher than at the moment of dual therapy introduction (185.8 mg/dl vs. 174.8 mg/dl- p<0.05). However, in patients previously not treated with TDF, there were no changes in lipid parameters during therapy. <i>Proteinuria</i> was observed in 13.2% of patients before the switch to dual therapy and in 7.1% of patients at week 48.</p><p>Conclusions</p><p>The investigated dual therapy was effective and safe. The observed increase in lipid parameters only concerned the patients who had used a TDF-based regimen prior to analysed dual treatment.</p></div

The diagnosis and treatment of primary dysmenorrhea

&nbsp;&nbsp;&nbsp;&nbsp; Primary dysmenorrhea is defined as pain in the pelvic area that occurs for no specific reason during menstrual cycle. Dysmenorrhea occurs in 50% to 90% of adolescent girls and women of reproductive age which makes it one of the most common causes of pelvic pain in women. The mechanism of this condition is overproduction of prostaglandins by the endometrium, causing uterine hypercontractility, thereby leading to uterine muscle ischemia, hypoxia and pain. Dysmenorrhea significantly reduces the quality of women life, often making it impossible to perform daily activities and, in addition, it may cause a mental stress that makes both professional and school life difficult. Despite this, females often consider these symptoms as a normal part of their menstrual cycle, which makes this disease underrated and untreated. Dysmenorrhea can be treated in a various ways such as non-pharmacological, pharmacological and surgical. However, women with a typical history of primary dysmenorrhea can commence empirical therapy without any additional tests. Hormonal contraception and nonsteroidal antiinflammatory drugs have proved to be effective in this treatment. However, if conventional treatment is contraindicated, alternative treatments such as topical heat, lifestyle modification, transcutaneous electrical nerve stimulation, dietary supplements, acupuncture, and acupressure may be used. Surgical treatment is possible, but it is used rarely and only in severe cases of treatment-resistant dysmenorrhea. However, it should be emphasized how important it is to exclude secondary causes of dysmenorrhea

Meeting the WHO 90% target : antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics

Introduction: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. Methods: Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients’ characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. Results: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01–2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08–2.01), p = 0.016], baseline lymphocyte CD4 count ≥200 cells/µL [OR:1.72 (95%CI:1.04–2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29–2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL [OR:2.08 (95%CI:1.01–4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52–5.26), p = 0.001]. Conclusions: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation