Autovaccines - potent tool against chronic vulvovaginal candidiasis.

OBJECTIVE: Our aim was to determine the effect of immunomodulatory therapy in women with chronic and recurrent vulvovaginal candidiasis (RVVC). BACKGROUND: We present recent highlights in the research into vaginal microbiome and consequences of chronic inflammation such as vulvovaginal candidiasis (VVC). VVC is a widespread vaginal infection primarily caused by Candida albicans. Experience of more than three episodes per year is defined as RVVC. METHODS: The strains were isolated from women suffering from the above infections as for the period of 2017 to 2021 and subsequently used in immunomodulatory treatment. The preparation and administration of autovaccination therapy was performed using standard methodology and procedures cited in the manuscript. RESULTS: In total, autovaccines were produced for 73 patients of whom 30 (41 %) were successfully cured by this treatment, 29 (40 %) experienced a partially successful treatment, and in the remaining 14 (19 %), the autovaccination therapy was ineffective. CONCLUSION: We provide current knowledge about alternative (autovaccine) treatment options for female patients with VVC and RVVC diseases and our experience with the outcomes after autovaccine administration that currently has a promising therapeutic potential (Tab. 2, Ref. 18). Text in PDF www.elis.sk Keywords: autovaccines, chronic infections, vulvovaginal candidiasis, recurrent, Candida albicans.

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine in patients with advanced-stage, classical Hodgkin lymphoma: A prespecified subgroup analysis of high-risk patients from the ECHELON-1 study.

Approximately one-third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high-risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON-1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first-line therapy after a median follow-up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4-7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537-0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4-7 (HR, 0.588; 95% CI, 0.386-0.894; p = 0.012). The most common adverse events (AEs) in A + AVD-treated versus ABVD-treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4-7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high-risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON-1 shows a favorable benefit-risk balance in high-risk patients.

Prospective study of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients who are not suitable for stem cell transplant or multi-agent chemotherapy.

Some patients with relapsed/refractory Hodgkin lymphoma (HL) are not considered suitable for stem cell transplant (SCT) and have a poor prognosis. This phase IV study (NCT01990534) evaluated brentuximab vedotin (1·8 mg/kg intravenously once every 3 weeks) in 60 patients (aged ≥18 years) with CD30-positive relapsed/refractory HL, a history of ≥1 prior systemic chemotherapy regimen, who were considered unsuitable for SCT/multi-agent chemotherapy. Primary endpoint was overall response rate (ORR) per independent review facility (IRF). Secondary endpoints included duration of response (DOR), progression-free survival (PFS) per IRF, overall survival (OS), proportion proceeding to SCT and safety. The ORR was 50%, with 12% CR; 47% proceeded to SCT. Median DOR was 4·6 months and median duration of CR was 6·1 months. After a median follow-up of 6·9 and 16·6 months, median PFS and OS were 4·8 months (95% confidence interval, 3·0-5·3) and not reached, respectively; estimated OS rate was 86% at 12 months. Most common adverse events (≥10%) were peripheral neuropathy (35%), pyrexia (18%), diarrhoea and neutropenia (each 10%). Brentuximab vedotin showed notable activity with a safety profile consistent with known toxicities, and may act as a bridge to SCT, enabling high-risk patients who achieve suboptimal response to frontline/salvage chemotherapy/radiotherapy to receive potentially curative SCT.

Can Rituximab Improve the Outcome of Patients with Nodular Lymphocyte-Predominant Hodgkin's Lymphoma?

BACKGROUND: Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma showing strong CD20 expression. The role of rituximab in treating NLPHL still needs clarification. METHODS: We retrospectively reviewed the outcome of 23 patients with NLPHL treated with rituximab alone or in combination with chemotherapy and/or radiotherapy as part of their first- or second-line treatment. RESULTS: The median follow-up of the whole group was 67 months, and all patients remained alive. Twenty-two patients achieved complete remission after rituximab-based therapy, and one of them relapsed 32 months after treatment. One patient treated with rituximab alone achieved partial remission and progressed 22 months after treatment. CONCLUSION: The prognosis of NLPHL is excellent. Rituximab combined with chemotherapy and/or radiotherapy appears to prevent disease progression/relapse.

High Emergence of Multidrug-Resistant Sequence Type 131 Subclade C2 among Extended-Spectrum ß-Lactamase (ESBL)-Producing Escherichia coli Isolated from the University Hospital Bratislava, Slovakia.

The expansion of sequence type 131 (ST131) extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) represents major worldwide challenges. E. coli strains originating from healthcare facilities (labeled No. 1 and No. 2) of the University Hospital Bratislava (UHB) were analyzed for ST131 emergence, including its (sub)lineages and clonal relatedness. Antimicrobial resistance was determined in most strains. Of a total of 354 E. coli strains, 263 (74.3%) belonged to ST131; of these, 177 (67.3%) were from No. 1. Generally, among 260 ST131 E. coli, clades A/B were confirmed in 20 (7.7%), while clade C was noted in 240 (92.3%) strains; within them, subclades were detected as follows: C0 (17; 7.1%), C1 (3; 1.2%), and C2 (220; 91.7%). Among fifteen randomly selected E. coli strains that were investigated for ST and clonal relatedness, seven STs were identified: eight (53.3%) ST131, two (13.3%) ST73, and one each (6.7%) of ST10, ST12, ST14, ST1193, and ST1196. From No. 1, two ST131 in the first internal clinic and one ST131 from No. 2 in the aftercare department were highly clonally related, suggesting possible epidemiological association. Antimicrobial resistance was as follows: ciprofloxacin 93.8%, ceftazidime 78.4%, meropenem 0%, fosfomycin 2.9% and nitrofurantoin 1.4%. Prevention of ESBL-producing E. coli dissemination, especially for ST131 clade C2, is inevitably necessary for reducing drug resistance and decreasing healthcare-associated infections.

Elevating the Standard of Care for Patients with Psoriasis: 'Calls to Action' from Epicensus, a Multistakeholder Pan-European Initiative.

INTRODUCTION: Despite advances in treatment options and the management of patients with psoriasis, considerable unmet needs remain. Our objective was to identify ways to elevate the standard of care for patients with psoriasis by combining the perspectives of three important stakeholders: patients, clinicians and payors, and define 'Calls to Action' designed to achieve the identified changes. METHODS: Eight themes relevant to elevating the standard of care were identified from an insights-gathering questionnaire completed by all three stakeholder groups. A modified Delphi exercise gained consensus on statements informed by the insights. Statements were then used to inspire 'Calls to Action' - practical steps that could be taken to realise the desired changes and elevate the standard of care. RESULTS: In total, 18 European experts (10 dermatologists, 3 payors and 5 patient representatives) took part in the Delphi process. Consensus was reached on statements relating to all eight themes: improve healthcare systems to better support multidisciplinary team working and digital services, real-world data generation and optimal use, improve patient access, elevate quality-of-life measures as the most important outcomes, involve patients in patient-centred and personalised approaches to care, improve the relevance and reach of guidelines, education, and multistakeholder engagement. 'Calls to Action' common to all three stakeholder groups recognised the need to capitalise on the shift to digital healthcare, the need for consistent input into registries to generate real-world evidence to support guideline development, and the necessity of educating patients on the benefits of reporting outcomes to generate real-world data. The enormous quality-of-life burden and psychological impact of psoriasis, as well as the clinical needs of patients must be better understood, including by healthcare commissioners, so that funding priorities are assessed appropriately. CONCLUSION: This unique initiative identified a practical 'Call-to-Action Framework' which, if implemented, could help improve the standard of care for patients with psoriasis.

Despite improvements in the management of psoriasis, there is room for the standard of care for patients to be improved further. The aim of the 'Epicensus' programme is to help realise improvements by bringing together three important stakeholder groups involved in the care of patients with psoriasis: dermatologists, payors and patient representatives. First, unmet needs were explored with these stakeholders and eight themes for change were identified: 1) improve healthcare systems to better support multidisciplinary team working and digital services; 2) optimise real-world data generation and use; 3) improve patient access; 4) elevate quality-of-life measures as the most important outcomes; 5) involve patients in people-centred and personalised approaches to care; 6) improve the relevance and reach of guidelines; 7) education; 8) multistakeholder engagement. Next, a panel of experts representing the three stakeholder groups took part in a consensus process (Delphi) to reach agreement on statements relating to each of the eight themes. The statements describe current problems and what needs to be changed to raise the standard of care for patients with psoriasis. Some of the problems identified are similar to those that existed a decade ago, showing that simply recognising what needs to change is not enough to bring about improvements: action must be taken. Therefore, the Epicensus participants met to produce specific 'Calls to Action'­ practical steps described in this publication that, if put into practice, should contribute to an improvement in the standard of care for patients with psoriasis.

Next-Generation Sequencing of Carbapenem-Resistant Klebsiella pneumoniae Strains Isolated from Patients Hospitalized in the University Hospital Facilities.

Carbapenem-resistant (CR) Klebsiella pneumoniae represents an urgent worldwide threat. We focused on CR K. pneumoniae in selected facilities of the University Hospital Bratislava (UHB) to investigate sequence types (STs), clonal relatedness, and antimicrobial resistance. Suspected carbapenem-nonsusceptible K. pneumoniae strains were obtained from hospitalized patients. Further examination included carbapenemase confirmation, cgMLST, and quantitative susceptibility testing. Of the total 41 CR K. pneumoniae strains, 26 (63.4%) were determined as ST11 in hospital No. 1; of these ST11, 22 (84.6%) were found in the first internal clinic. Six (14.6%) ST258 and three (7.3%) ST584 occurred in hospital No. 2; the most, i.e., four (66.7%), ST258 were detected in the geriatric clinic. In hospital No. 3, we found two (4.8%) ST584 and one (2.4%) ST258. Of the ST11 set, 24 (92.3%) produced NDM-1. Furthermore, seven (87.5) ST258 and five (100%) ST584 strains generated KPC-2. Antimicrobial resistance was as follows: ertapenem 97.6%, meropenem 63.4%, tigecycline 7.3%, eravacycline 7.3%, and colistin 2.5%. We revealed a presumably epidemiological association of ST11 with transmission, particularly in the first internal clinic of hospital No. 1, while ST258 and ST584 were related to interhospital dissemination between medical facilities No. 2 and No. 3. It is essential to prevent the circulation of these pathogens within and between healthcare facilities.

Impact of psoriatic disease on women aged 18 to 45: Results from a multinational survey across 11 European countries.

BACKGROUND: Plaque psoriasis (PSO) is a long-term inflammatory condition that can cause concomitant joint symptoms (psoriatic arthritis [PsA]) in up to 30% of patients. The impact of psoriatic disease on disease outcomes and quality of life is greater in women than men. OBJECTIVE: We evaluated the impact of psoriatic disease on women aged 18 to 45 years across Europe. METHODS: Women aged 18 to 45 years with moderate to severe PSO, PsA, or PSO + PsA (PSO with progression to PsA) and prior biologic experience were recruited from market research panels and patient association groups of the International Federation of Psoriasis Associations, European Federation of Psoriasis Patient Associations, and Arthritis Ireland and asked to complete a survey. Questions covered social and psychological wellbeing, employment, and family planning. Question types included 5- or 7-point agreement scales, where the highest/lowest two ratings were considered agreement/disagreement, respectively. The results are reported as proportions of those who selected the answer, divided by overall respondents for each question. Women were not required to answer all questions. RESULTS: Survey respondents (N = 573) had a diagnosis of PSO (n = 236), PsA (n = 173), or PSO + PsA (n = 164). Women self-reported similar mean scores for physical (57.0 of 100) and mental (59.0 of 100) health. A fifth (21%) had not achieved their desired career due to PSO/PsA; career dissatisfaction and increased sick leave were linked to poor mental health. Some women reported having a limited social life (33%), smaller families (34%), and being more likely to adopt children (27%) due to PSO/PsA. A quarter of women (27%) reported not understanding enough about PSO/PsA (nonmembers vs. members of patient association groups: 37% vs. 8%). CONCLUSION: Our findings highlight the considerable burden of psoriatic disease on women of childbearing age. Increased provision of information tailored to women, training for health care professionals, and shared decision-making between patients and health care professionals may help better support women with psoriatic disease.

Mitotically active deep juvenile xanthogranuloma.

Juvenile xanthogranuloma is a relatively rare cutaneous tumor of histiocytic origin, occurring mainly in neonates, children, and young people in the first 2 decades of life. An occurrence in adults is rare. Very rare is also a "deep" subcutaneous and intramuscular localization of this tumor that is called in such case as "deep juvenile xanthogranuloma." A very uncommon variant of this tumor is the so-called mitotically active xanthogranuloma, which was described in the literature only in a single case. We present an interesting case of the mitotically active intramuscular juvenile xanthogranuloma of the upper arm in a 28-year-old woman. Before surgical excision, the tumor was examined by fine-needle aspiration biopsy. A diagnosis of deep malignant melanoma or alveolar rhabdomyosarcoma was considered. One year after the total excision, the patient is free of disease. In the presented case, we emphasize cytologic-histologic correlation. In the differential diagnosis, we considered especially an atypical diffuse giant cell tumor of tendon sheaths and joints (extra-articular pigmented villonodular synovitis) and some rare types of soft tissue leiomyosarcoma, such as epitheloid leiomyosarcoma and leiomyosarcoma with prominent osteoclast-like giant cells.

Mullerianosis of the urinary bladder: report of a case with suggested metaplastic origin.

Mullerianosis of the urinary bladder is a very rare and morphologically complex tumor-like lesion. It is composed of several types of mullerian-type lesions, including endometriosis, endocervicosis, and endosalpingiosis. This disease occurs in women of the reproductive age group. In the pathogenesis, implantative and metaplastic origins have been suggested, and they are still under discussion. In the present report, a rare case of this lesion in a 41-year-old woman is described. The bladder contained, in addition to typical mullerianosis, glandular cystitis with focal intestinal metaplasia. An interesting and, to our knowledge, hitherto unreported feature was a rare continuity between the glands of mullerianosis and glands of glandular cystitis. The histologic and immunohistochemical findings in the present case support strongly the metaplastic origin of mullerianosis.

[Development of Beta-lactamase resistance in enterobacteria]. / Vývoj rezistencie Beta-laktamáz u enterobaktérií.

Enterobacteria produce elementary chromosomal enzymes, Beta-lactamases of class A: TEM and SHV (Escherichia coli, Klebsiella pneumoniae). These can give rise to plasmid-coded broad-spectrum Beta-lactamases (ESBL) discovered in 1980 (E. coli, K. pneumoniae, Enterobacter cloacae). The first cefotaximase (CTX-M, MEN-1) was reported in Europe in 1990. This enzyme is far more active against cefotaxime than against ceftazidime and aztreonam. Chromosomal hyperpoduction of K1 Beta-lactamase differs from all other ESBLs due its sensitivity to ceftazidime (Klebsiella oxytoca). However, not all enterobacteria are resistant only because of ESBLs, but also as a result of the action of chromosomally or plasmid coded AmpC Beta-lactamase of class C (MIR-1, CMY-1, BIL-1, FOX-1, MOX-1, DHA-1, ACC-1), resistant to Beta-lactamase inhibitors and to cefoxitin (Enterobacter spp., Proteus vulgaris, Citrobacter freundii, Morganelle spp., Serratia spp.). With the loss of outside-membrane porins (OMP) they can become resistant to carbapenem an tibiotics. The 100% resistance of enterobacteria to carbapenems that so far exists in this country is elsewhere in the world compromised by the incidence of carbapenem-hydrolysing plasmid-determined Beta-lactamase of class B (IMP-1, VIM-1) and of class A (KPC-1) in K. pneumoniae, (SME-1) in Serratia marcescens and (IMI-1, NMC-A) in E. clocae. Carbapenemases in enterobacteria are only effective in the presence of impermeability and other resistance mechanisms.

Involvement of virulence properties and antibiotic resistance in Escherichia coli strains causing pyelonephritis in children.

A total of 145 Escherichia coli strains causing pyelonephritis in children were investigated for the prevalence of genes encoding the following virulence factors (VFs): P fimbria (67.6 %), S fimbria (53.8 %), AFA adhesins (2.8 %), cytotoxic necrotizing factor 1 (37.9 %), α-hemolysin (41.4 %), and aerobactin (71.7 %). One hundred and thirty-six (93.8 %) isolates harbored at least one of the virulence genes detected in the present study. Statistically significant co-occurrent presence of two VF genes was found for α-hly-cnf1, α-hly-sfa, cnf1-sfa (p<0.001), and α-hly-pap (p=0.001). Twenty-six profiles of VF genes were detected in this study. The combinations of aer-pap and aer-pap-sfa-α-hly-cnf1 were presented with the highest frequency-both of them in 28 isolates (19.3 %). All E. coli strains included in the study were susceptible to meropenem, amikacin, and tobramycin; the highest frequency resistance was found toward ampicillin (43.4 %), piperacillin (31.7 %), tetracycline (15.9 %), and trimethoprim/sulfamethoxazole (11.7 %). The resistance to the other tested antimicrobial drugs did not exceed 3 % incidence. Overall, 55.9 % strains were susceptible to all tested anti-infective agents. Antimicrobial resistance of E. coli strains toward trimethoprim/sulfamethoxazole statistically significantly correlated with the presence of α-hly (p<0.001), sfa (p<0.01), and cnf1 (p<0.05).

Morphologic diversity of malignant neoplasms arising in preexisting spiradenoma, cylindroma, and spiradenocylindroma based on the study of 24 cases, sporadic or occurring in the setting of Brooke-Spiegler syndrome.

The authors present a series of 24 malignant neoplasms arising in preexisting benign spiradenoma (20), cylindroma (2), and spiradenocylindroma (2). Nineteen patients (12 females, 7 males; age range, 41 to 92 y) had a solitary neoplasm (size range, 2.2 to 17.5 cm; median 4 cm), whereas the remaining 5 (4 females, 1 male; age range, 66 to 72 y) manifested clinical features of Brooke-Spiegler syndrome (BSS), an autosomal dominantly inherited disease characterized by widespread, small, benign neoplasms on which background larger malignant lesions appeared. Microscopically, all cases showed the residuum of a preexisting benign neoplasm. The malignant components of the lesions were variable and could be classified into 4 main patterns, occurring alone or in combination: 1) salivary gland type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG); 2) salivary gland type basal cell adenocarcinoma-like pattern, high-grade (BCAC-HG); 3) invasive adenocarcinoma, not otherwise specified (IAC-NOS); and 4) sarcomatoid (metaplastic) carcinoma. In 1 case of IAC-NOS, an in situ adenocarcinoma was also found, presumed to have evolved from an adjacent adenomatous and atypical adenomatous component. Cases harboring a sarcomatoid carcinoma featured a malignant epithelial component composed of varying combinations of BCAC-HG, BCAC-LG, IAC-NOS, or squamous cell carcinoma, whereas the sarcomatoid component appeared as either a pleomorphic or spindle-cell sarcoma. Additionally, in 2 cases there were foci of heterologous chondrosarcomatous differentiation and in 1 case there was rhabomyosarcomatous differentiation. Of the 21 patients with available follow-up (range, 3 mo-15 y; average 4.8 y; median 3.5 y), 10 were without evidence of disease, 1 was alive with metastatic disease, 1 was alive with BSS, 3 developed local recurrences, 4 had died of disease, and 2 were dead of other causes. The histologic pattern of the malignant neoplasm correlated to some extent with the clinical course. BCAC-LG neoplasms showed a less aggressive course, with local recurrences but no distant metastases, whereas the BCAC-HG neoplasms typically followed a highly aggressive course resulting in the death 3 of 6 patients with BCAC-HG. Patients with sarcomatoid carcinoma had a relatively good survival. Molecular genetic investigations revealed no mutations in the CYLD gene in the 4 sporadic cases investigated. One patient with BSS revealed a novel missense germline mutation in exon 14 (c. 1961T>A, p. V654E), whereas a living descendant of another deceased patient demonstrated a recurrent nonsense germline mutation in exon 20 (c. 2806C>T, p. R936X). Given the morphologic diversity and complexity of the neoplasms in question, we propose using a more specific terminology with the precise description of the neoplasm components, rather than generic and less informative terms such as "spiradenocarcinoma" or "carcinoma ex cylindroma."