Study of gut microbiome alterations in plaque psoriasis patients compared to healthy individuals.

Introduction: Many studies have shown significant alterations in the gut microbiome of patients with psoriasis compared to healthy controls. Aim: The primary objective of the current research was to explore the impact of gut microbiome composition on the progression and severity of plaque psoriasis. Material and methods: A total of 20 patients with moderate-to-severe psoriasis and 20 healthy individuals were recruited and provided a stool sample to assess the gut microbiome. After the samples were prepared according to the NGS library preparation workflow, they were sequenced using the Illumina platform and the report was generated that underwent statistical analysis. Results: The microbiome profiles of psoriasis patients exhibited significant differences compared to healthy controls as evidenced by the statistical analysis of various bacterial genera, with the median abundance significantly lower in psoriasis patients compared to healthy controls (p = 0.033). The analysis of the Firmicutes-to-Bacteroidetes ratio, a commonly evaluated marker of dysbiosis, did not reach statistical significance (p = 0.239). However, there was a noticeable trend towards a higher median ratio in psoriasis patients compared to healthy controls. The ratio did not show significant associations with PASI or BSA but trends towards significance with DLQI (B = -12.11, p = 0.095). Conclusions: Overall, the above findings underscore the importance of the gut microbiome in psoriasis and suggest that modulation of specific bacterial genera, especially that with significant differences, could be a potential strategy for therapeutic intervention. Targeting these depleted genera through microbiome-based interventions, such as probiotic supplementation or faecal microbiota transplantation, could potentially help to restore gut homeostasis and alleviate the inflammatory burden in psoriasis.

Correlation between angiotensin-converting-enzyme 2 gene polymorphisms and systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is a disease with cardiovascular impairment and polymorphisms of the gene coding of angiotensin-converting-enzyme 2 (ACE2) may account for its development. Three single nucleotide polymorphisms of ACE2 (C>G rs879922, G>A rs2285666 and A>G rs1978124) were found to increase the risk for development of arterial hypertension (AH) and cardiovascular (CVS) diseases in different ethnicities. We investigated associations of polymorphisms rs879922, rs2285666 and rs1978124 with the development of SSc. METHODS: Genomic DNA was isolated from whole blood. Restriction-fragment-length polymorphism was used for genotyping of rs1978124, while detection of rs879922 and rs2285666 was based on TaqMan SNP Genotyping Assay. Serum level of ACE2 was assayed with commercially available ELISA test. RESULTS: 81 SSc patients (60 women, 21 men) were enrolled. Allele C of rs879922 polymorphism was associated with significantly greater risk for development of AH (OR=2.5, p=0.018), but less frequent joint involvement. A strong tendency to earlier onset of Raynaud's phenomenon and SSc was seen in carriers of allele A of rs2285666 polymorphism. They had lower risk for development of any CVS disease (RR=0.4, p=0.051) and tendency to less frequent gastrointestinal involvement. Women with genotype AG of rs1978124 polymorphism had significantly more frequent digital tip ulcers and lower serum level of ACE2. CONCLUSIONS: Polymorphisms of ACE2 may account for the development of AH and CVS disorders in SSc patients. Strong tendencies to more frequent occurrence of disease specific characteristics distinct to macrovascular involvement will require further studies evaluating significance of ACE2 polymorphisms in SSc.

Role of short courses on nailfold capillaroscopy in obtaining abilities for the identification of microvasculopathy in patients with Raynaud's phenomenon.

INTRODUCTION: An early distinction between "normal" and "abnormal" capillaroscopic pattern during the first visit to a dermatologist has a crucial significance for a diagnostic management of Raynaud's phenomenon (RP). There exists a question about the level of expertise sufficient to evaluate the microcirculation. AIM: To evaluate the utility of short courses on NFC among dermatologists and medical students in obtaining sufficient abilities for the identification of microvasculopathy in patients with RP using videocapillaroscope and handheld dermoscope. METHODS: Both groups participated in 1-h course on NFC. Before the course, participants were asked to classify 20 videocapillaroscopic and 10 dermoscopic capillaroscopic pictures into "normal" or "abnormal" pattern. Each picture was displayed on a separate slide MS PowerPoint for 10 s. The evaluation was repeated soon after the course. RESULTS: A total of 36 dermatologists and 49 medical students were enrolled. The rate of properly classified dermoscopic and videodermoscopic pictures increased after the course in both groups, but students improved the accuracy of classification on dermoscopic pictures to the greater extent than dermatologists. The rate of correctly recognized pictures with "abnormal" pattern was significantly greater than ones with "normal" pattern at the baseline and after the course, independently of imagining tool. CONCLUSIONS: Short courses on NFC may improve the classification of capillaroscopic images, even in medical staff with no previous experience in NFC. The recognition of capillaroscopic abnormalities seems to be easier than obtaining the confidence that evaluated picture has "normal pattern."

Utility of phototherapy in patients with systemic sclerosis: Systematic review.

Phototherapy is a recommended treatment regimen for different scleroderma spectrum disorders, but so far it has been included neither by European nor by worldwide experts committee in recommendations for the treatment of systemic sclerosis (SSc). The aim of the study was to revisit the utility of dermatological phototherapy in patients with SSc. PubMed using medical subject headings was searched to identify studies evaluating response to dermatological phototherapy in SSc patients. Both UVA1 (340-400 nm) and PUVA (psoralen plus UVA) treatments were found to reduce skin thickening and increase skin elasticity, therefore allowing for the improvement of joint tension mobility, especially in hands. At least several papers showed efficacy of phototherapy in patients who remained non-responsive to previous immunosuppressive therapies. The most probable mechanisms of action of phototherapy in SSc include inhibition of T-cells and prevention from dermal fibrosis. Although most data on the efficacy of phototherapy come from small experimental studies and case reports, phototherapy based on UVA of wavelength manifests relatively mild spectrum of side effects and this should be considered as a treatment option for SSc with dominant cutaneous involvement.

The impact of face masks on acne-prone skin in Polish young adults during COVID-19 pandemic.

COVID-19 pandemic raised many problems for patients with acne-prone skin: a limited access to health care services, the necessity of developing telemedical consultations also in dermatology, and the usage of face masks. The aim of the study was to investigate the influence of respiratory protective measures (type of masks, wearing time during the day) on declared skin condition in patients already diagnosed with acne or reporting acne for the first time. The study was conducted in Poland among 1420 responders using the original authors' questionnaire, of which 1274 responders were included in the final sample. Acne exacerbations were reported as being more frequent and more severe in women than in men. Changing cosmetic products, facial skin decontamination before or after applying masks, the number of days per week that a mask was worn were related to acne exacerbation. The type of mask had no significant impact on the occurrence of acne lesions. Respondents noted that masks contribute significantly to skin condition worsening by exacerbating existing and causing new acne lesions. This phenomenon was particularly observable in women, in whom, according to the research results, new lesions appeared much more frequently. Therefore, there is a need to develop new ways of limiting acne exacerbation during COVID-19 pandemic.

The role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathophysiology of psoriasis and systemic lupus erythematosus.

Inflammation and atherogenic dyslipidaemia are often observed in skin diseases and represent an increased risk of cardiovascular disorders. Proprotein convertase subtilisin/kexin type 9 plays an important role in the regulation of serum low-density lipoprotein cholesterol levels. Its biological role, however, seems to go much beyond the regulation of cholesterol metabolism. The article presents potential pathophysiological links between inflammatory process and lipid disorders based on the example of psoriasis and systemic lupus erythematosus.

Psoriasis and Gut Microbiome-Current State of Art.

Psoriasis is a chronic, immune-mediated inflammatory disease that affects around 125 million people worldwide. Several studies concerning the gut microbiota composition and its role in disease pathogenesis recently demonstrated significant alterations among psoriatic patients. Certain parameters such as Firmicutes/Bacteroidetes ratio or Psoriasis Microbiome Index were developed in order to distinguish between psoriatic and healthy individuals. The "leaky gut syndrome" and bacterial translocation is considered by some authors as a triggering factor for the onset of the disease, as it promotes chronic systemic inflammation. The alterations were also found to resemble those in inflammatory bowel diseases, obesity and certain cardiovascular diseases. Microbiota dysbiosis, depletion in SCFAs production, increased amount of produced TMAO, dysregulation of the pathways affecting the balance between lymphocytes populations seem to be the most significant findings concerning gut physiology in psoriatic patients. The gut microbiota may serve as a potential response-to-treatment biomarker in certain cases of biological treatment. Oral probiotics administration as well as fecal microbial transplantation were most reported in bringing health benefits to psoriatic patients. However, the issue of psoriatic bacterial gut composition, its role and healing potential needs further investigation. Here we reviewed the literature on the current state of the relationship between psoriasis and gut microbiome.

The influence of medical education level on the Jagiellonian University Collegium Medicum medical students' knowledge concerning oral hormonal contraceptive pills.

In December 2014 the authors carried out a research among Jagiellonian University Collegium Medicum medical students in a form of a questionnaire which consisted of two parts: personal information and multiple choice test concerning student's knowledge on OCPs. It showed that the level of medical education, defined as the year of study, increases student's knowledge about oral hormonal contraceptive pills. New program of study introduced from academic year 2012/2013 gives students wider knowledge on OCPs at earlier stage of education. Factors as female sex, usage of OCPs by student or his partner, positive attitude towards recommending OCPs to future patients show positive correlation with student's knowledge.

Pigmented Paget's disease of the nipple.

Pigmented Paget's disease of the nipple (PPD) is an uncommon variant of Paget's disease. An accumulation of melanin within the lesion imparts a brow color to the affected area, so the lesion might clinically as well as histologically mimic melanoma. We present a case of PPD in a 60-year-old woman.

Significance of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) for the Monitoring of Treatment Response to Cyclosporine in Patients with Psoriasis.

Neutrophil gelatinase-associated lipocalin (NGAL) may promote development of inflammation in psoriasis, whereas proprotein convertase subtilisin/kexin type 9 (PCSK9) may account for dyslipidemia in some psoriatic patients. The aim of the study was to analyze the influence of cyclosporine therapy on serum levels of NGAL and PCSK9 in patients with psoriasis vulgaris. METHODS: Serum samples were obtained before and after three months cyclosporine therapy. Patients were grouped into responders and non-responders to cyclosporine depending on whether they achieved at least 50% reduction of Psoriatic Activity Score Index (PASI), or not. Serum levels of PCSK9 and NGAL were assayed using commercially available ELISA tests. Lipid levels were measured with an enzymatic method. RESULTS: There were 40 patients enrolled. A significant decrease in serum NGAL level was seen in cyclosporine responders. No similar dependance was found for PCSK9. Serum PCSK9 concentration correlated with total cholesterol (TChol) and LDL at baseline and after three month treatment. CONCLUSIONS: Cyclosporine therapy contributes to the reduction of the NGAL serum but not the PCSK9 concentration. Correlation between the PCSK9 serum level and TChol as well as LDL concentration may help to understand drug induced dyslipidemia after cyclosporine.

Clinical assessment of patients with systemic sclerosis: is there a place for thermography?

Recurrent changes of temperature and persistence of cooling along fingers at the room temperature make hands the most frequent region of interest for thermography in systemic sclerosis (SSc). The aim of this study was to evaluate dependance of temperature in hands on a subtype of the disease, immune profile of antinuclear antibodies (ANA), and lung involvement. There were 29 patients with limited cutaneous involvement (lcSSc) and 10 patients with diffuse cutaneous disease (dcSSc) enrolled for the study. To compare measurements to normal values, there were enrolled 29 healthy volunteers (control group). All participants were submitted to thermography with handheld camera FLIR One Pro for iOS, attached to mobile phone iPhone 11, at the fixed temperature of 21 °C. Measurements included average temperature (Tavg) over nailfolds in thumbs and fingers II-V, as well as the difference in average temperatures (TΔ) between metacarpus of the hand and its thumb and fingers II-V. Both thumbs and fingers II-V remained cooler in subjects with dcSSc compared to those with lcSSc. This implicated a significantly greater TΔ along thumbs and fingers II-V in dcSSc group. Although Tavg at nailfolds in SSc patients was not lower than in healthy controls, TΔ remained significantly more pronounced in both lcSSc and dcSSc subjects. A positivity to ACA in lcSSc group was found to be associated with significantly lower Tavg and more pronounced TΔ in fingers II-V than the presence of anti-Scl70 antibodies. Temperature measurements remained statistically independent on a presence of ILD in lcSSc group, but both thumbs and fingers II-V in dcSSc group were warmer in case of lung involvement. The study showed the dcSSc subtype, the positivity of ACA in lcSSc, but not lung involvement were associated with poorer thermal control in the hands of SSc patients. A comparison to healthy controls highlighted the weakness of temperature measurements at nailfolds (Tavg) but increased the value of TΔ in thermography of hands.

Torasemide-induced Vascular Purpura in the Course of Eosinophilic Granulomatosis with Polyangiitis.

Torasemide is a loop diuretic with a molecule that is chemically similar to the sulphonamides described as eosinophilic granulomatosis with polyangiitis (EGPA) triggering drugs. The presented case is probably the first description of torasemide-induced vascular purpura in the course of EGPA. Any diagnosis of vasculitis should be followed by an identification of drugs that may aggravate the disease. A 74-year-old patient was admitted to the Department of Dermatology with purpura-like skin lesions on the upper, and lower extremities, including the buttocks. The lesions had appeared around the ankles 7 days before admission to the hospital and then started to progress upwards. The patient complained on lower limb paresthesia and pain. Other comorbidities included bronchial asthma, chronic sinusitis, ischemic heart disease, mild aortic stenosis, arterial hypertension, and degenerative thoracic spine disease. The woman had previously undergone nasal polypectomy twice. She was on a constant regimen of oral rosuvastatin 5 mg per day, spironolactone 50 mg per day, metoprolol 150 mg per day, inhaled formoterol 12 µg per day, and ipratropium bromide 20 µg per day. Ten days prior to admission, she was commenced on torasemide at a dose of 50 mg per day prescribed by a general practitioner due to high blood pressure. Doppler ultrasound upon admission to the hospital excluded deep venal thrombosis. The laboratory tests revealed leukocytosis (17.1 thousand per mm3) with eosinophilia (38.6%), elevated plasma level of C-reactive protein (119 mg per L) and D-dimers (2657 ng per mm3). Indirect immunofluorescent test identified a low titer (1:80) of antinuclear antibodies, but elevated (1:160) antineutrophil cytoplasmic antibodies (ANCA) in the patient's serum. Immunoblot found them to be aimed against myeloperoxidase (pANCA). A chest X-ray showed increased vascular lung markings, while high-resolution computed tomography revealed peribronchial glass-ground opacities. Microscopic evaluation of skin biopsy taken from the lower limbs showed perivascular infiltrates consisting of eosinophils and neutrophils, fragments of neutrophil nuclei, and fibrinous necrosis of small vessels. Electromyography performed in the lower limbs because of their weakness highlighted a loss of response from both sural nerves, as well as slowed conduction velocity of the right tibial nerve and in both common peroneal nerves. Both clinical characteristics of skin lesions and histopathology suggested a diagnosis of EGPA, which was later confirmed by a consultant in rheumatology. The patient was commenced on prednisone at a dose of 0.5 mg per kg of body weight daily and mycophenolate mofetil at a daily dose of 2 g. The antihypertensive therapy was modified, and torasemide was replaced by spironolactone 25 mg per day. The treatment resulted in a gradual regression of skin lesions within a few weeks. The first report of EGPA dates back to 1951. Its authors were Jacob Churg and Lotte Strauss. They described a case series of 13 patients who had severe asthma, fever, peripheral blood eosinophilia, and granulomatous vasculitis in microscopic evaluation of the skin. Three histopathological criteria were then proposed, and Churg-Strauss syndrome was recognized when eosinophilic infiltrates in the tissues, necrotizing inflammation of small and medium vessels, and the presence of extravascular granulomas were observed together in a patient (1). Only 17.4% of patients met all three histopathological criteria, and the diagnosis of the disease was frequently delayed despite of its overt clinical picture (2). In 1984, Lanham et al. proposed new diagnostic criteria which included the presence of bronchial asthma, eosinophilia in a peripheral blood smear >1.5 thousand per mm3, and signs of vasculitis involving at least two organs other than the lungs (3). Lanham's criteria could also delay the recognition of the syndrome before involvement of internal organs, and the American College of Rheumatology therefore established classification criteria in 1990. These included the presence of bronchial asthma, migratory infiltrates in the lungs as assessed by radiographs, the presence of abnormalities in the paranasal sinuses (polyps, allergic rhinitis, chronic inflammation), mono- or polyneuropathy, peripheral blood eosinophilia (>10% of leukocytes must be eosinophils), and extravascular eosinophilic infiltrates in a histopathological examination. Patients who met 4 out of 6 criteria were classified as having Churg-Strauss syndrome (4). The term EGPA was recommended to define patients with Churg-Strauss syndrome in 2012 (5). EGPA is a condition with low incidence (0.11-2.66 cases per million) and morbidity. It usually occurs in the fifth decade of life (6,7), although 65 cases reports of EGPA in people under 18 years of age could be found in the PubMed and Ovid Medline Database at the end of 2020 (8). The etiopathogenesis of the disease has not been fully explained so far. Approximately 40-60% of patients are positive to pANCA (9), but the role of these antibodies in the pathogenesis of EGPA remains unclear. They are suspected to mediate binding of the Fc receptor to MPO exposed on the surface of neutrophils. Subsequently, this may active neutrophils and contribute to a damage of the vascular endothelium (9,10). Glomerulonephritis, neuropathy, and vasculitis are more common in patients with EGPA who have detectable pANCA when compared with seronegative patients. There are at least several drugs which potentially may EGPA. The strongest association with the occurrence of EGPA was found with the use of leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast), although they are commonly used in the treatment of asthma, which is paradoxically one of the complications of the syndrome (13). Although no relationship has been demonstrated so far between the occurrence of EGPA and the intake of drugs from the groups used by the presented patient, a clear time relationship can be observed between the commencement of torasemide and the onset of symptoms in our patient. To date, only three cases of leukocytoclastic vasculitis have been reported after the administration of torasemide. Both of them developed cutaneous symptoms of the disease within 24 hours of the administration of torasemide in patients with no previous history of drug hypersensitivity, but they disappeared quickly within 8-15 days after drug discontinuation (14,15). The chemical structure of torasemide is similar to the molecule of sulfonamides which were previously found to be a triggering factors for EGPA (12). This drug belongs to the group of loop diuretics classified as sulfonamide derivatives. A comparison of the chemical structure of torasemide and sulphanilamide molecules is presented in Figure 1. The clear time relationship between starting the administration of torasemide and the occurrence of purpura-like lesions suggests that it was an aggravating factor for EGPA in our patient. A coexistence of several disorders (asthma, nasal polyps, symptoms of peripheral neuropathy) in our patient suggest EGPA could have developed in her years before oral intake of torasemide. The sudden onset of skin symptoms shows torasemide to be possible inducing factor for the development of vascular purpura in patients suffering from EGPA but without previous cutaneous involvement.

Vitamin D-The Nutritional Status of Post-Gastrectomy Gastric Cancer Patients-Systematic Review.

Gastric cancer is a malignant neoplasm of the gastrointestinal tract, with one of the standard treatment methods remaining gastrectomy. The authors conducted a systemic review of the Medline and Embase databases concerning the serum vitamin D level in post-gastrectomy gastric cancer patients, regarding all articles published until 22 May 2022 according to the PRISMA guidelines. 18 studies with a total number of 908 gastric cancer survivors were included in the analysis. The initial rate of vitamin D deficiency in gastric cancer patients undergoing gastrectomy appears to be similar to the global population deficiency. In post-gastrectomy survivors, the level of 25(OH)D may remain stable or decrease, while the level of 1, 25(OH)2D remains normal. Supplementation with vitamin D results in an improvement in its serum concentration and positively affects bone mineral density, which is gradually reduced in post-gastrectomy survivors. Combining vitamin D supplementation with calcium and bisphosphonates enables us to obtain better results than vitamin D and calcium only. The type of surgery influences the level of serum vitamin D and its metabolites, with total or partial gastrectomy and maintenance of the duodenal food passage remaining the most important factors. There is a strong need for randomized, controlled trials that would investigate this matter in the future.

Microbiome Modulation as a Therapeutic Approach in Chronic Skin Diseases.

There is a growing quantity of evidence on how skin and gut microbiome composition impacts the course of various dermatological diseases. The strategies involving the modulation of bacterial composition are increasingly in the focus of research attention. The aim of the present review was to analyze the literature available in PubMed (MEDLINE) and EMBASE databases on the topic of microbiome modulation in skin diseases. The effects and possible mechanisms of action of probiotics, prebiotics and synbiotics in dermatological conditions including atopic dermatitis (AD), psoriasis, chronic ulcers, seborrheic dermatitis, burns and acne were analyzed. Due to the very limited number of studies available regarding the topic of microbiome modulation in all skin diseases except for AD, the authors decided to also include case reports and original studies concerning oral administration and topical application of the pro-, pre- and synbiotics in the final analysis. The evaluated studies mostly reported significant health benefits to the patients or show promising results in animal or ex vivo studies. However, due to a limited amount of research and unambiguous results, the topic of microbiome modulation as a therapeutic approach in skin diseases still warrants further investigation.

Analysis of forensic medical opinions issued in criminal cases of alleged medical error in obstetrics at the Department of Forensic Medicine, Jagiellonian University Medical College, in 2010-2016.

AIM OF THE STUDY: Analysis of forensic medical opinions in the field of obstetrics prepared at the Department of Forensic Medicine, Jagiellonian University Medical College in Krakow, in 2010-2016, in order to evaluate changes in the number of filed cases involving an alleged medical error over the years, and determine the most common situations where medical errors are suspected by patients, and the most prevalent types of medical errors in obstetrics. MATERIAL AND METHODS: The opinions were divided into two groups. In the first group, the medical management was appropriate, while in the second group medical errors were identified. The medical errors were categorised as diagnostic/therapeutic, technical, and organisational. The effects of medical errors were classified as death, impairment to health, exposure to death, and exposure to impairment to health, by considering them separately for post-natal women, and for foetuses and neonates (during the first days of life). RESULTS: A total of 73 forensic medical opinions were analysed. In 25 cases, a medical error was identified. The most common situations in which a medical error was committed, and in which the suspicion of medical error proved to be unfounded, were listed. Overall, there were 17 diagnostic/therapeutic errors, 7 organisational errors, and 4 technical errors. In cases where a medical error was identified, there were 15 deaths, and in cases without a medical error - 31 deaths. CONCLUSIONS: It was found that 66% of the analysed forensic medical opinions involved no medical errors. In most of these cases, a therapeutic failure occurred, including perinatal haemorrhage, tight wrapping of the umbilical cord around the foetal neck (nuchal cord), premature birth, and septic complications. A few cases involved uncooperative patients. The most prevalent medical error was failure to perform or delaying a caesarean section when it was needed (because of emergency or urgent indications). The second most common medical error was related to incorrect CTG interpretation.