Influence of infection on the distribution patterns of NIH-Chronic Prostatitis Symptom Index scores in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition for which the etiological determinants are still poorly defined. To better characterize the diagnostic and therapeutic profile of patients, an algorithm known as UPOINT was created, addressing six major phenotypic domains of CP/CPPS, specifically the urinary (U), psycho-social (P), organ-specific (O), infection (I), neurological/systemic (N) and muscular tenderness (T) domains. An additional sexual dysfunction domain may be included in the UPOINT(S) system. The impact of the infection domain on the severity of CP/CPPS symptoms is a controversial issue, due to the contradictory results of different trials. The aim of the present retrospective study was to further analyze the extent to which a positive infection domain of UPOINTS may modify the pattern of CP/CPPS symptom scores, assessed with the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). In a cohort of 935 patients that was divided on the basis of the presence or absence of prostatic infection, more severe clinical symptoms were shown by the patients with infection (median NIH total score: 24 versus 20 points in uninfected patients; P<0.001). Moreover, NIH-CPSI score distribution curves were shifted towards more severe symptoms in patients with a positive infection domain. Division of the patients into the six most prominent phenotypic clusters of UPOINTS revealed that the 'prostate infection-related sexual dysfunction' cluster, including the highest proportion of patients with evidence of infection (80%), scored the highest number of NIH-CPSI points among all the clusters. To assess the influence of the infection domain on the severity of patients' symptoms, all subjects with evidence of infection were withdrawn from the 'prostate infection-related sexual dysfunction' cluster. This modified cluster showed symptom scores significantly less severe than the original cluster, and the CPSI values became comparable to the scores of the five other clusters, which were virtually devoid of patients with evidence of infection. These results suggest that the presence of pathogens in the prostate gland may significantly affect the clinical presentation of patients affected by CP/CPPS, and that the infection domain may be a determinant of the severity of CP/CPPS symptoms in clusters of patients phenotyped with the UPOINTS system. This evidence may convey considerable therapeutic implications

Complicated Lemierre Syndrome Caused by Streptococcus gordonii and Possible Rickettsial Co-Infection in a Patient with Thrombophilia Predisposition

Aims: Lemierre syndrome is a life-threating condition characterized by recent oropharyngeal infection, internal jugular vein thrombosis, and anaerobic septicemia. It is usually caused by Fusobacterium necrophorum. Methods: A young Romanian male presented with fever and rigors, mild tachypnea, hypoxia, sore throat, decayed teeth, and tenderness of the left carotid triangle. Laboratory examination indicated severe sepsis with disseminated intravascular coagulation, acute renal failure, and acute respiratory distress syndrome while the Doppler ultrasonography of the carotids revealed left internal jugular venous thrombosis. The patient was administered piperacillin/tazobactam and vancomycin intravenously, doxycycline orally, and anti-coagulation by enoxaparin based on the diagnosis of Lemierre syndrome. Meanwhile, he was complicated by bilateral diffuse pulmonary cavities and encapsulated pleural effusions and so transcutaneous drainage was performed. The patient was discharged after a month and continued his treatment with oral phenoxypenicillin and doxycycline until full radiographic improvement. He was switched to oral anti-coagulation by vitamin-K antagonists and was referred to a hematologist, a vascular-surgeon, and a dentist. Results: Streptococcus gordonii was isolated from the patient’s blood and pleural fluid cultures and serology for Rickettsial spp. IgM was positive. Thrombophilia genetic tests revealed three minor mutations for fibrinogen-455, plasminogen activator inhibitor-1, and methylenetetrahydrofolate reductase. According to the literature, S. gordonii is not usually a causative agent and Rickettsial spp. have as yet not been correlated with Lemierre syndrome. The failure of left jugular vein recanalization shows a possible causative role of the underlying thrombophilic predisposition. Discussion: Because of the syndrome’s rarity and the atypical microorganisms isolated in this case, increased awareness is advised for its diagnosis and the underlying mechanisms involved in its genesis. The role of anti-coagulation is debatable

Zygomycosis in Immunocompromised non-Haematological Patients

Zygomycoses caused by fungi of the mucorales order (mucormycoses) are emerging fungal diseases with a high fatality rate. The most important risk factors include neutropenia or functional neutropenia, diabetic ketoacidosis, iron overload, major trauma, prolonged use of corticosteroids, illicit intravenous drug (ID) use, neonatal prematurity, malnourishment, and maybe a previous exposure to antifungal agents with no activity against zygomycetes, such as voriconazole and echinocandins

Multirezistencija i integroni kod sojeva bakterije Esherichia coli izolovanih kod brojlera u Grčkoj

Enteric faecal flora of food-producing animals such as poultry is a potential reservoir for antimicrobial resistance genes which can be transferred to human pathogens via the food chain. The present study investigated 47 strains of Enterobacteriaceae recovered from a variety of chicken specimens for their resistance to 18 antimicrobial agents and the presence of integrons, and analyzed the association between integrons and antimicrobial susceptibility. Multidrug resistance was found in 82.9% of the isolates. The presence of integrons was shown in 68.1% of the strains tested: 42.5% carried a class 1 integron, 10.6% carried a class 2 integron, and 14.9% had both class 1 and 2 integrons. An unusual cassette aacA4-catB3-dfrA1 was revealed in two class 1 integron-positive isolates. The association between the presence of an integron and multidrug resistance was significant (p lt 0.05). The mercury resistance gene, merA, was found in 44.4% of strains with class 1 integron, indicating the role of Tn21 transposon in dissemination of integrons within the samples studied. The study gives baseline information on the resistance problem and its genetic background in contemporary poultry Enterobacteriaceae in Greece, and suggest the need for the introduction of surveillance programs to monitor antimicrobial resistance that can be potentially transmitted to humans.Crevna mikroflora životinja koje se koriste u ishrani ljudi, uključujući i crevnu mikrofloru živine, predstavlja potencijalni rezervoar gena rezistencije na antibiotike za bakterije koje su humani patogeni. U toku ove studije je iz različitih uzoraka uzetih od 29 zdravih i 18 bolesnih brojlera izolovano ukupno 47 sojeva Enterobacteriaceae od kojih je čak 43 identifikovano kao Escherichia coli. Kod svih izolata ispitana je osetljivost na 18 antibiotika, prisustvo integrona, kao i moguća povezanost integrona i rezistencije na antibiotike. Preko 80% izolata (82,9%) je bilo multirezistentno. Integroni su bili prisutni kod 68,1% izolata i to: integroni klase 1 kod 42,5%, integroni klase 2 kod 10,6%, a obe klase kod 14,9% sojeva. Treba istaći da je kod dva izolata sa klasom 1 integrona ustanovljeno prisustvo kasete aacA4-catB3-dfrA1, koja je do sada opisivana samo kod vrste Pseudomonas aeruginosa. Statistička analiza pokazala je značajnu povezanost prisustva integrona i multirezistencije (p lt 0,05). Gen merA, odgovoran za rezistenciju na živu, detektovan je kod 44,4% izolata sa klasom 1 integrona, što ukazuje na ulogu Tn21 transpozona u diseminaciji integrona unutar ispitivane grupe izolata. Ova studija pružila je prvi uvid u problem rezistencije i genetičku osnovu rezistencije izolata enetrobakterija kod živine u Grčkoj. Dobijeni rezultati ukazuju na potrebu uvođenja programa kontinuiranog praćenja rezistencije ovih bakterija, s obzirom na postojanje mogućnosti za transfer njihovih gena rezistencije na humane patogene

Small European states in the hybrid warfare era : the cases of Cyprus, Malta, and Estonia

The increasing number and complexity of hybrid threat activities forces small states, especially those with limited access to material resources, to reassess their foreign and defence policies. While the variable of ‘smallness’ may be sufficient to justify their overall engagement in dealing with conventional security threats, in the hybrid arena this is not the case. Pressure is amplified in establishing or maintaining a status of a reliable mediator, partner, and strategic communicator vis-à-vis their multilateral relations with other states or organisations to which they belong. This paper focuses on how small European states, with specific reference to Cyprus, Malta, and Estonia, need to develop adjustable yet resilient policies in accommodating security needs vis-à-vis hybrid threats, that are not only pertinent to their security, but also to that of the EU bloc. As the line between war and peace becomes more blurred due to hybrid threats, the small states’ security shortcomings may also become a security problem for the EU bloc. We argue that the nature of hybrid threats is such that hybrid activities can be utilised to hurt bigger states in a bloc by exploiting the small states’ vulnerabilities. Both the defensive and foreign policy collaborations of small states with bigger states have been, and are constantly being, re-evaluated to tackle and prevent such problems. As such, two objectives are identified in this approach. The first is the small states’ quest to appear as reliable partners within the bloc. The second is to avoid being the weakest security link in the bloc’s defence against hybrid threats. This unfamiliar environment for small states prompts us to rethink security from their perspective against complex and hybrid threats, and in relation to their security role as members of large organisations such as the EU.peer-reviewe

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies

Clonotypic Analysis of Immunoglobulin Heavy Chain Sequences in Patients with Waldenström’s Macroglobulinemia: Correlation with<i>MYD88</i>L265P Somatic Mutation Status, Clinical Features, and Outcome

We performedIGHclonotypic sequence analysis in WM in order to determine whether a preferentialIGHgene rearrangement was observed and to assessIGHVmutational status in blood and/or bone marrow samples from 36 WM patients. In addition we investigated the presence ofMYD88L265P somatic mutation. AfterIGHVDJ locus amplification, monoclonal VDJ rearranged fragments were sequenced and analyzed.MYD88L265P mutation was detected by AS-PCR. The most frequent family usage wasIGHV3(74%);IGHV3-23andIGHV3-74segments were used in 26% and 17%, respectively. Somatic hypermutation was seen in 91% of cases.MYD88L265P mutation was found in 65,5% of patients and absent in the 3 unmutated. These findings did not correlate with clinical findings and outcome. Conclusion.IGH genes’repertoire differed in WM from those observed in other B-cell disorders with a recurrentIGHV3-23andIGHV3-74usage; monoclonalIGHVwas mutated in most cases, and a high but not omnipresent prevalence ofMYD88L265P mutation was observed. In addition, the identification of 3 patients with unmutatedIGHVgene segments, negative for theMYD88L265P mutation, could support the hypothesis that an extra-germinal B-cell may represent the originating malignant cell in this minority of WM patients.</jats:p

ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients

The European Conference on Infections in Leukemia (ECIL) provides recommendations for diagnostic strategies and prophylactic, pre-emptive or targeted therapy strategies for various types of infection in patients with hematologic malignancies or hematopoietic stem cell transplantation recipients. Meetings are held every two years since 2005 and evidence-based recommendations are elaborated after evaluation of the literature and discussion among specialists of nearly all European countries. In this manuscript, the ECIL group presents the 2015-update of the recommendations for the targeted treatment of invasive candidiasis, aspergillosis and mucormycosis. Current data now allow a very strong recommendation in favor of echinocandins for first-line therapy of candidemia irrespective of the underlying predisposing factors. Anidulafungin has been given the same grading as the other echinocandins for hemato-oncological patients. The beneficial role of catheter removal in candidemia is strengthened. Aspergillus guidelines now recommend the use of either voriconazole or isavuconazole for first-line treatment of invasive aspergillosis, while first-line combination antifungal therapy is not routinely recommended. As only few new data were published since the last ECIL guidelines, no major changes were made to mucormycosis recommendations