Two new species of Phaeohelotium (Leotiomycetes: Helotiaceae) from Chile and their putative ectomycorrhizal status.

Species of the genus Phaeohelotium (Leotiomycetes: Helotiaceae) are cup fungi that grow on decaying wood, leaves, litter, and directly on soil. Northern Hemisphere species are primarily found on litter and wood, whereas in the Southern Hemisphere the genus includes a mix of saprotrophs as well as taxa that grow on soil in association with ectomycorrhizal trees. The diversity of this genus has not been fully explored in southern South America. Here we describe two species from Chile, Phaeohelotium maiusaurantium sp. nov. and Ph. pallidum sp. nov., found on soil in Patagonian Nothofagaceae-dominated forests. We present macro- and micromorphological descriptions, illustrations, and molecular phylogenetic analyses. The two new species are placed in Phaeohelotium with high support in our 15-locus phylogeny as well as phylogenetic reconstructions based on the internal transcribed spacer (ITS) region of the nuclear ribosomal RNA gene. Our ITS phylogeny places both Ph. maiusaurantium and Ph. pallidum in a well-supported subclade that includes ectomycorrhizal root tip samples from Australasia. Similar species can be separated from these new taxa based on morphological characteristics, biogeography, substrate, and sequence data. In addition, two unnamed species from Chilean Nothofagaceae forests (Phaeohelotium sp. 1 and Phaeohelotium sp. 2) are documented from scant collections and sequence data and await description until more material becomes available. Citation: Grupe II AC, Smith ME, Weier A, Healy R, Caiafa MV, Pfister DH, Haelewaters D, Quandt CA (2022). Two new species of Phaeohelotium (Leotiomycetes: Helotiaceae) from Chile and their putative ectomycorrhizal status. Fungal Systematics and Evolution 10: 231-249. doi: 10.3114/fuse.2022.10.10.

Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

A review of Hyphodiscaceae.

In a recently published classification scheme for Leotiomycetes, the new family Hyphodiscaceae was erected; unfortunately, this study was rife with phylogenetic misinterpretations and hampered by a poor understanding of this group of fungi. This manifested in the form of an undiagnostic familial description, an erroneous familial circumscription, and the redescription of the type species of an included genus as a new species in a different genus. The present work corrects these errors by incorporating new molecular data from this group into phylogenetic analyses and examining the morphological features of the included taxa. An emended description of Hyphodiscaceae is provided, notes and descriptions of the included genera are supplied, and keys to genera and species in Hyphodiscaceae are supplied. Microscypha cajaniensis is combined in Hyphodiscus, and Scolecolachnum nigricans is a taxonomic synonym of Fuscolachnum pteridis. Future work in this family should focus on increasing phylogenetic sampling outside of Eurasia and better characterising described species to help resolve outstanding issues. Citation: Quijada L, Baral HO, Johnston PR, Pärtel K, Mitchell JK, Hosoya T, Madrid H, Kosonen T, Helleman S, Rubio E, Stöckli E, Huhtinen S, Pfister DH (2022). A review of Hyphodiscaceae. Studies in Mycology 103: 59-85. doi: 10.3114/sim.2022.103.03.

[Influence of the working model on the education of young urologists : Education through the ages]. / Auswirkung eines Arbeitszeitmodells auf den Facharzt für Urologie : Eine Ausbildung im Wandel der Zeit.

BACKGROUND: There is a trend of increasing discontent of urologic residents with educational programs. One point being mentioned is lack of time during residency for education and self-training. We analyzed the available time for education in our department depending on the used working model through the last 25 years. MATERIALS AND METHODS: We calculated the absolute availability of residents during their residency for working models in 1996, 2000, 2007 and 2017. As a basis we used the working model of 1996 as no compensatory time-off for being on call was used. All days on which a delayed start is planned and no schedule in daily routine is possible had been excluded from education time. The numbers implemented in the regulation on further education in the corresponding years had been used to calculate the expenditure of time on the basis of median length of the different intervention. In addition, the patient numbers on the ward and our outpatient clinic had been documented over time. RESULTS: With increasing patient numbers in the in- and outpatient clinic there is a continuous decreasing time available for education. The absolute available time in our department is calculated to be 3.1 years compared to 5 years in 1996. With the first day of training a resident has to complete 66.9 min of self-contained diagnostics or interventions per day in addition to clinical routine and administration to meet the requested numbers of the regulation on further education. CONCLUSIONS: The limited time being available for the educational program is improved by the current regulation of education. To teach the complex segments of urology there is an urgent need for a well-structured curriculum, which should be used nationwide.

[COVID-19 in urology : Influence of the pandemic on telemedicine, education and surgery]. / COVID-19 im urologischen Alltag : Einfluss der Pandemie auf Telemedizin, Ausbildung und Operationen in der Urologie.

The COVID-19 (coronavirus disease 2019) pandemic has caused a worldwide economic and clinical disaster. During times with the highest infection rates, clinical practice for all specialties including urology shifted to the emergency setting. Proper patient selection needs to be done to avoid infection; however, there is a fine line between postponing surgery and negatively affecting the outcome of the disease to be treated. The rapid integration of telemedicine has helped to keep up outpatient medical care, interdisciplinary communication and education. Nevertheless, surgical education of urological residents initially fell behind. The real impact of the COVID-19 pandemic on urology will probably first be seen after the awaited vaccine and control of COVID-19.

Wanted on Agave americana! Hymenobolus agaves, an overlooked introduced pathogen in the western palearctic region.

Hymenobolus agaves has been reported only in Europe and Africa on the American plant Agave americana (Asparagaceae). This fungus has never been found in the native range of its host, in arid ecosystems of northern and central Mexico and Texas, USA. It has been suggested to be a pathogen that can kill its host. The fungus grows on succulent leaf bases of the plant. The morphology - black apothecia with a hymenium that disintegrates when asci mature and dark ornamented ascospores - make this species very distinctive, but it has been collected and reported only a few times since its first description. Its systematic position has been unclear, and it has been treated as incertae sedis, that is of uncertain placement, in Leotiomycetes. With recent collections and additional data on the ecology of H. agaves, we use integrative taxonomy (DNA sequences, morphology, ecology) to show its relationships is with Cenangiaceae.

Resurrecting the genus Geomorium: Systematic study of fungi in the genera Underwoodia and Gymnohydnotrya (Pezizales) with the description of three new South American species.

Molecular phylogenetic analyses have addressed the systematic position of several major Northern Hemisphere lineages of Pezizales but the taxa of the Southern Hemisphere remain understudied. This study focuses on the molecular systematics and taxonomy of Southern Hemisphere species currently treated in the genera Underwoodia and Gymnohydnotrya. Species in these genera have been identified as the monophyletic /gymnohydnotrya lineage, but no further research has been conducted to determine the evolutionary origin of this lineage or its relationship with other Pezizales lineages. Here, we present a phylogenetic study of fungal species previously described in Underwoodia and Gymnohydnotrya, with sampling of all but one described species. We revise the taxonomy of this lineage and describe three new species from the Patagonian region of South America. Our results show that none of these Southern Hemisphere species are closely related to Underwoodia columnaris, the type species of the genus Underwoodia. Accordingly, we recognize the genus Geomorium described by Spegazzini in 1922 for G. fuegianum. We propose the new family, Geomoriaceae fam. nov., to accommodate this phylogenetically and morphologically unique Southern Hemisphere lineage. Molecular dating estimated that Geomoriaceae started to diverge from its sister clade Tuberaceae c. 112 MYA, with a crown age for the family in the late Cretaceous (c. 67 MYA). This scenario fits well with a Gondwanan origin of the family before the split of Australia and South America from Antarctica during the Paleocene-Eocene boundary (c. 50 MYA).

[Surgical treatment of intracaval tumor relapse after radical tumor nephrectomy in locally advanced renal cell carcinoma]. / Chirurgische Therapie des intrakavalen Tumorrezidivs nach radikaler Tumornephrektomie lokal fortgeschrittener Nierenzellkarzinome.

BACKGROUND: About 4-10% of patients with renal cell carcinoma (RCC) demonstrate intracaval tumor thrombi at the time of diagnosis. Furthermore, 2-3% of patients might develop local relapses of which intracaval recurrences represent a rare event with fewer than 15 cases reported in the literature. We report the diagnosis, surgical technique, perioperative complications, and oncological outcome in an additional 6 cases. PATIENTS AND METHODS: Between 2008 and 2019, 6 patients were treated with isolated intracaval relapse of RCC. All patients had undergone radical nephrectomy with thrombectomy in the past. The mean time between first surgery and relapse was 45.2 (6-114) months and the mean age of patients was 75 (70-80) years: 2, 3 and 1 patient demonstrated thrombus level II, III, and IV, respectively. A thoracoabdominal and a transperitoneal surgical approach was chosen in 4 and 2 patients, respectively. Perioperative complications were reported according to the Clavien-Dindo classification. Relapse-free, cancer-specific and overall survival were calculated with the Kaplan-Meier method. RESULTS: The cava thrombus could be resected completely in all cases. The mean time of surgery was 330 (260-510) min and the mean blood loss was 1500 (300-6500) ml. Clavien-Dindo grade II and IV complications developed in 2 and 1 patients, respectively. The 90-day readmission rate and mortality were 0%. After a mean follow-up of 32.3 (6-96) months, 5 patients are relapse-free and 1 patient developed pulmonary and hepatic metastases managed by immuno-oncological therapy. One patient died 27 months postoperatively due to multiple myeloma. CONCLUSION: Secondary thrombectomy for isolated intracaval tumor thrombus relapse represents a challenging surgery which is associated with a high oncological control rate and tolerable surgery-related morbidity. This type of surgery should be performed in centres with significant expertise in radical nephrectomy for locally advanced disease and thrombus surgery.

Cones, needles and wood: Micraspis (Micraspidaceae, Micraspidales fam. et ord. nov.) speciation segregates by host plant tissues.

Micraspis acicola was described more than 50 years ago to accommodate a phacidium-like fungus that caused a foliar disease of Picea mariana. After its publication, two more species were added, M. strobilina and M. tetraspora, all of them growing on Pinaceae in the Northern Hemisphere, but each species occupying a unique type of host tissue (needles, cones or wood). Micraspis is considered to be a member of class Leotiomycetes, but was originally placed in Phacidiaceae (Phacidiales), later transferred to Helotiaceae (Helotiales) and recently returned to Phacidiales but in a different family (Tympanidaceae). The genus remains poorly sampled, and hence poorly understood both taxonomically and ecologically. Here, we use morphology, cultures and sequences to provide insights into its systematic position in Leotiomycetes and its ecology. Our results show that the genus should not be included in Tympanidaceae or Phacidiaceae, and support the erection of a new family and order with a unique combination of morphological features supported by molecular data.

Geodina (Pezizomycetes: Wynneaceae) has a single widespread species in tropical America.

Geodina salmonicolor is shown to be a synonym of G. guanacastensis, the type and only species of the genus. Comparisons of ITS rDNA sequences of a paratype and two recent collections of G. guanacastensis with published ITS sequences of G. salmonicolor, from the Dominican Republic, show that these are nearly identical. When G. salmonicolor was erected no sequences of the type species were available. Morphological comparisons supports the conspecificity. Details regarding the description of G. salmonicolor are pointed out. A four-gene phylogeny places Geodina and Wynnea as a supported sister group to the rest of the Sarcoscyphaceae. Species in these genera share morphological traits of cyanophobic spore markings, dark angular outer excipular cells that give rise to hairs and the origin of several apothecia from a common basal stalk. Their occurrence on soil rather than on wood or plant material distinguish them from other Sarcoscyphaceae. Based on morphology, phylogenic relationships and trophic interactions we erect a new family, Wynneaceae, for Geodina and Wynnea.

[Targeted molecular therapy and immunotherapy for prostate cancer]. / Molekulare zielgerichtete Therapie und Immuntherapie des Prostatakarzinoms.

For decades, the treatment of advanced prostate cancer was mainly based on the manipulation of the androgen receptor-controlled proliferation pathway. Chemotherapy only played an additional important role with the advent of taxanes. The progress in translational research in recent years has led to innovations in the therapeutic environment. With the decoding of the homologous repair deficiency (HRD) machinery and its ability to be influenced by PARP inhibitors, targeted therapies moved into the therapeutic focus for selected patients. The first positive phase III study for PARP inhibitors is already available. In addition, immunotherapy for the treatment of prostate cancer, which is now widely used in oncology, is also making progress; both checkpoint inhibitors and bispecific antibodies have shown clinically useful activities. Cellular therapies such as CAR T cells, which are directed against prostate-specific membrane antigen (PSMA), are still at an early stage of development. In this review, the authors provide a summary of the basic principles and clinical development of these new therapies.

[Radium-223 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) : The androgen receptor-independent active agent in the therapeutic sequence]. / Radium-223 zur Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) : Der androgenrezeptorunabhängige Wirkstoff in der therapeutischen Sequenz.

BACKGROUND: Radium-223 improves overall survival and preserves quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases and no known visceral metastases. Radium-223 can be used in combination with a luteinizing hormone releasing hormone (LHRH) analogue and as part of a sequential treatment scheme if disease progresses after at least two prior lines of systemic mCRPC therapies or if no other available systemic treatment is eligible. OBJECTIVES: Today physicians are faced with a previously unknown multitude and complexity of options for the treatment of mCRPC. An increasing number of clinical trials contribute to the dynamics of the therapeutic landscape. Radium-223 was approved for mCRPC treatment in 2013. Up to now the recommendations of use have been adjusted several times. Highlighting recent clinical trials and practice, this paper explores the position of radium-223 within the therapeutic sequence and outlines key elements for the interdisciplinary cooperation between uro-oncologists and nuclear medicine specialists. RESULTS: The mode of action of radium-223 does not depend on the androgen receptor (AR) pathway. Thus, it is an option in the therapeutic sequence when the efficacy of other agents is reduced by resistance. Furthermore, the efficacy of prior or subsequent medications are neither reduced nor enhanced by radium-223. The opportunity of an AR-independent and survival-prolonging medication should be taken as soon as the indication criteria are met because the incidence of visceral metastases increases during disease progression. According to current mCRPC guidelines, the osteoprotective use of bisphosphonates or denosumab is recommended, before treatment with radium-223 is started or resumed.

[Interdisciplinary education in urology: innovations for better training]. / Verbundweiterbildung in der Urologie: Innovationen für eine bessere Ausbildung.

The current version of the urology training program will concentrate on the mediation of competences and skills in various fields of action for outpatient urology instead of persisting on the minimum and reference numbers of surgical and diagnostic procedures. However, the following fields of action must be fulfilled: microbiology, andrology and systemic cancer therapy. There is justifiable concern that various institutions will lose their permission for a complete 5­year residency program based on the above-mentioned demands since not all institutions have all subspecialties in urology. Those institutions need to define new ways of residency training such as interdisciplinary programs within their own institution between disciplines like pediatric surgery, gynecology and medical oncology. Other options are combined training programs between regional urology departments with different main focuses or training programs between institutions and urologists in private practice. There is an unmet need to improve residency training as well as board examinations by new structures and a reliable curriculum. Based on the changed main focuses of the new version of urology training, we need to discuss the future of residency programs. It might be helpful to discuss two different types of urology training with a common trunk for the first three years followed by a more outpatient-based residency training for the general urologist and a more specialized training for the inpatient urologist to be educated in complex treatment modalities. An open mind to broadening our own horizon, respectful discussion with other departments and the development of common, reliable and interdisciplinary contents represent indispensable prerequisites to realize such an innovative future training program.

[Treatment situation in metastastic Castration Naive Prostate Cancer (mCRPC) and the implications on clinical routine]. / Therapiesituation beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) und die Auswirkungen im klinischen Alltag.

There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naïve stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.

Morphological species of Gloeandromyces (Ascomycota, Laboulbeniales) evaluated using single-locus species delimitation methods.

In this paper, new species and formae of the genus Gloeandromyces (Ascomycota, Laboulbeniales) are described and illustrated. These are: Gloeandromyces dickii sp. nov. on Trichobius joblingi from Nicaragua and Panama; G. pageanus f. alarum f. nov. on Tri. joblingi from Panama; G. pageanus f. polymorphus f. nov. on Tri. dugesioides and Tri. joblingi from Panama and Trinidad; and G. streblae f. sigmomorphus f. nov. on Tri. joblingi from Panama. Gloeandromyces pageanus on Tri. dugesioides from Panama as described in Nova Hedwigia 105 (2017) is referred to as G. pageanus f. pageanus. Support for these descriptions of species and formae comes from phylogenetic reconstruction of the large subunit ribosomal DNA and from the application of species delimitation methods (ABGD, bPTP, GMYC). Host specialization results in phylogenetic segregation by host species in both G. pageanus and G. streblae and this may represent a case of incipient speciation. A second mechanism driving diversity involves position-induced morphological adaptations, leading to the peculiar morphotypes that are associated to growing on a particular position of the integument (G. pageanus f. alarum, G. streblae f. sigmomorphus).

On the co-occurrence of species of Wynnea (Ascomycota, Pezizales, Sarcoscyphaceae) and Armillaria (Basidiomycota, Agaricales, Physalacriaceae).

Species of the genus Wynnea are collected in association with a subterranean mass generally referred to as a sclerotium. This is one of the few genera of the Sarcoscyphaceae not associated with plant material - wood or leaves. The sclerotium is composed of hyphae of both Armillaria species and Wynnea species. To verify the existence of Armillaria species in the sclerotia of those Wynnea species not previously examined and to fully understand the structure and nature of the sclerotium, molecular data and morphological characters were analyzed. Using nuclear ITS rDNA sequences the Armillaria species co-occurring with Wynnea species were identified from all examined material. These Armillaria symbionts fall into two main Armillaria groups - the A. gallica-nabsnona-calvescens group and the A. mellea group. Divergent time estimates of the Armillaria and Wynnea lineages support a co-evolutionary relationship between these two fungi.

A phase II study of temsirolimus added to low-dose weekly carboplatin and paclitaxel for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Background: Activating events along the PI3K/mTOR pathway are common in head and neck squamous cell carcinomas (HNSCC), and preclinical studies suggest additive or synergistic effects when combining mTORC1 inhibitors with carboplatin and paclitaxel chemotherapy. Patients and methods: In this single-institution phase II study, the combination of temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m2 administered on days 1 and 8 of a 21-day cycle was evaluated in 36 patients with recurrent and/or metastatic (R/M) HNSCC. The primary end point was objective response rate after two cycles of treatment. Secondary end points include the safety and tolerability profile and overall survival. Correlative studies with exome mutational analysis were performed in pre-treatment biopsy samples from 21 patients. Results: Fifteen (41.7%) patients had an objective response, which were all partial responses, and 19 (52.3%) patients had stable disease as best response. The two patients who were designated as 'non-responders' were removed from study prior to two cycles of treatment, but are included in the efficacy and safety analyses. The median duration on study was 5.3 months and the median progression-free survival and overall survival were 5.9 months (95% confidence interval, 4.8-7.1) and 12.8 months (95% confidence interval, 9.8-15.8), respectively. The most common grade 3 and 4 adverse events were hematologic toxicities. Three (3.8%) patients developed neutropenic fever on study. Three of four patients with PIK3CA mutations experienced tumor regressions, and responses were also seen in patients with other genetic alterations in the PI3K/mTOR pathway. Conclusion: The combination of temsirolimus with low-dose weekly carboplatin and paclitaxel appears to have meaningful clinical efficacy in the treatment of R/M HNSCC. This regimen has a relatively high response rate compared to other treatments evaluated in R/M HNSCC, and potential associations with genetic alterations in the PI3K/mTOR pathway should be further explored.