The need for strong clinical leaders - Transformational and transactional leadership as a framework for resident leadership training

Background: For the purpose of providing excellent patient care, residents need to be strong, effective leaders. The lack of clinical leadership is alarming given the detrimental effects on patient safety. The objective of the study was to assess whether a leadership training addressing transactional and transformational leadership enhances leadership skills in residents. Methods: A volunteer sample of 57 residents from postgraduate year one to four was recruited across a range of medical specialties. The residents took part in an interventional controlled trial. The four-week IMPACT leadership training provided specific strategies for leadership in the clinical environment, addressing transactional (e.g. active control, contingent reward) and transformational leadership skills (e.g. appreciation, inspirational motivation). Transactional and transformational leadership skill performance was rated (1) on the Performance Scale by an external evaluator blinded to the study design and (2) self-assessed transformational and transactional leadership skills. Both measures contained items of the Multifactor Leadership Questionnaire, with higher scores indicating greater leadership skills. Results: Both scores were significantly different between the IMPACT group and the control group. In the IMPACT group, the Performance Scale increased 15% in transactional leadership skill performance (2.10 to 2.86) (intervention effect, 0.76;95% CI, 0.40 to 1.13;p < .001, eta(2) = 0.31) and 14% in transformational leadership skill performance (2.26 to 2.94) (intervention effect, 0.68;95% CI, 0.27 to 1.09;p < .001, eta(2) = 0.22). The self-assessed transactional skills revealed a 4% increase (3.83 to 4.03) (intervention effect, 0.20;95% CI, 0.08 to 0.33;p < .001, eta 2 = 0.18) and a 6% increase in transformational leadership skills (3.54 to 3.86) (intervention effect, 0.31;95% CI, 0.02 to 0.40;p < .001, eta(2) = 0.53). Discussion and conclusions: These findings support the use of the transactional and transformational leadership framework for graduate leadership training. Future studies should incorporate time-latent posttests, evaluating the stability of the behavioral performance increase

Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways

The EHA Research Roadmap : Malignant Lymphoid Diseases

Peer reviewe

New perspectives in extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue: the Vienna experience

Hintergrund: Während das gastrische MALT Lymphom bereits ausführlich charakterisiert wurde, findet man in der Literatur nur wenige Daten zu „wild-typ“ Kollektiven (Patienten aller Lokalisationen). Insbesondere klinische Details sowie potentielle prognostische Faktoren extragastrischer/ eradikations-refraktärer MALT Lymphom Patienten in Hinblick auf unterschiedliche Therapiemodalitäten wurden erst wenig erforscht. Zielsetzung: Ziel dieser Arbeit war es, anhand eines neu generierten Datensets mit Einschluss aller MALT Lymphom Patienten an der Medizinischen Universität Wien 1999-2015, das Kollektiv dieser Patienten systematisch zu analysieren und neben genauer Auswertung klinischer Charakteristika und Therapie-spezifischer Langzeitdaten auch mögliche prognostische Faktoren zu untersuchen. Ergebnisse: Mit 327 dokumentierten Patienten ist dies eines der größten MALT Lymphom Kollektive, das je analysiert wurde (medianer Beobachtungszeitraum 55.2 Monate). Die Ergebnisse dieser Thesis werden in Form einer kumulativen Arbeit basierend auf vier Publikationen präsentiert: 1.) MALT Lymphome des Auges: Eine Analyse von 60 orbitalen MALT Lymphom Patienten unterstreicht die gute Prognose dieser Subgruppe unabhängig von der initialen Therapiestrategie. Während an den meisten Zentren die Strahlentherapie als bevorzugte Therapiemodalität angesehen wird, zeigen unsere Daten, dass auch eine systemische Erstlinientherapie als valide Option anzusehen ist. 2.) Geschlechts-spezifische Aspekte: Gender-spezifische Analysen sollten 2017 eine Selbstverständlichkeit darstellen, dennoch gab es bisher keinerlei Daten diesbezüglich zum MALT Lymphom. Wir präsentieren eine detaillierte Auswertung sämtlicher klinischer und therapeutischer Charakteristika in Hinblick auf mögliche Unterschiede zwischen weiblichen und männlichen Patienten (Patientenanzahl = 327). 3.) Prädiktive Marker: Im Rahmen dieses Projektes wurde der Zusammenhang zwischen immunhistochemischer Expression von CRBN/ MUM1 und Ansprechen auf Lenalidomid-basierte Therapie beim MALT Lymphom untersucht. Im Gegensatz zu Analysen bei anderen Tumorentitäten konnte keine Assoziation nachgewiesen werden. Basierend auf diesen Ergebnissen kann eine routinemäßige Bestimmung derzeit nicht empfohlen werden. 4.) Prognostischer Score für MALT Lymphome: Die erarbeiteten Daten dieser Thesis waren Teil einer europäischen Kooperation zur Entwicklung eines MALT Lymphom-spezifischen prognostischen Index. Zusammenfassung: Im Rahmen dieser Arbeit konnten nicht nur die spezifische Charakteristika der MALT Lymphom Patienten an der Medizinischen Universität Wien erarbeitet werden, sondern es wurden auch potentielle prognostische und prädiktive Marker evaluiert.Background: Helicobacter pylori positive gastric mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) has been extensively studied but there are only limited data on the typical features of larger “wild-type” MALT lymphoma collectives, and particularly prognostic factors for non-gastric or eradication refractory patients including assessment of predictive markers for different treatment strategies need to be further investigated. Aim: The aim of this thesis was to evaluate systematically clinico-pathological and treatment-related features of MALT lymphoma patients and investigate potential prognostic markers based on a newly generated dataset of all patients treated at the Medical University Vienna, Department of Medicine I, Clinical Division of Oncology 19992015. Results: With a total of 327 patients documented and analyzed within this thesis, this is one of the largest collectives reported to date (median follow-up time 55.2 months). Results are presented in form of a cumulative thesis including four publications arising from these data: 1.) Ocular adnexal MALT lymphoma: An analysis of 60 patients with ocular adnexal lymphoma confirms the excellent prognosis of this distinct subgroup irrespective of the initial treatment approach. In contrast to recent data evaluating particularly radiotherapy as first line therapy, we suggest that also systemic or antibiotic treatment is reasonable. 2.) Gender-specific aspects: Acknowledgement of gender-related aspects should be standard in clinical research 2017. However, there are no data addressing this issue for MALT lymphoma. We present the first systematic analysis on gender-specific aspects in terms of clinico-pathological features, treatment and outcome in a large collective of MALT lymphoma patients (n = 327). 3.) Potential predictive markers: CRBN and MUM1 have both been suggested as potential predictive markers for response to IMiDs. We have assessed the association of immunohistochemical expression of CRBN/ MUM1 and response to lenalidomide in 46 MALT lymphoma patients. In contrast to prior results, there was no clear relation between CRBN/ MUM1 expression and outcome. Our data will possibly avoid over-testing of these two respective markers. Further investigations are warranted. 4.) Prognostic score for MALT lymphoma: Data documented within this thesis contributed to the development of a new prognostic tool for the disease of MALT lymphoma. Conclusion: To conclude, the data assessed within this thesis contribute to further characterization of MALT lymphoma in terms of clinico-pathological features, prognostic factors and novel treatment approaches and offer a more concise knowledge on sub-populations and long-term outcome following different therapeutic strategies. The documented collective appears to be well representative for this entity and will most potentially allow to generate further hypotheses and support planning of future projects.submitted by Barbara Kiesewetter-WiederkehrAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Dissertation, 2017OeBB(VLID)246173

My burning issues in neuroendocrine tumours (NET)

Several compounds have recently been approved for the systemic treatment of advanced well-differentiated neuroendocrine tumours (NET) of gastroenteropancreatic (GEP) or lung origin. Based on the PROMID and CLARINET trials, somatostatin analogues (SSA) are the preferred first-line approach for all GEP-NET and offerin addition to antiproliferative effectsdurable symptomatic relief for hormonally active tumours. The mTOR inhibitor everolimus has been approved for progressive GEP- and lung-NET and is a widely used drug in this setting. Furthermore, recent results have underlined the high efficacy of somatostatin-receptor targeting radionuclide therapy (PRRT) in somatostatin-receptor positive midgut tumours and PRRT is now considered standard treatment for midgut-NET progressing on SSA. The optimal application of PRRT in somatostatin receptor positive NET with non-midgut site is currently an issue of discussion and should be decided on an individually basis in multidisciplinary boards. Following new insights in the genetic landscape of NET, “hot topics” in recent months include optimal treatment of the recently defined NET G3 and preliminary data on immunotherapy.(VLID)361993

Clinical relevance of molecular aspects in extranodal marginal zone lymphoma: a critical appraisal.

Peer reviewed: TrueExtranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is among the more common types of lymphoma accounting for up to 8% of newly diagnosed lymphoma cases. As opposed to other B-cell lymphomas, however, no predominant genetic hallmark has been defined in MALT lymphoma, but different localizations appear to be affected by different, sometimes distinct changes. Nonetheless, a high proportion of these genetic changes reported in MALT lymphomas dysregulate the pathways leading to NF-kB activation. t(11;18)(q21;q21)/BIRC3::MALT1 appears to be MALT lymphoma specific and is found in 24% of gastric and 40% of pulmonary MALT lymphomas. The translocation is associated with more disseminated disease in gastric MALT lymphoma and is found in a large percentage of patients whose lymphoma is unresponsive to antibiotic eradication of Helicobacter pylori. In addition to t(11;18)(q21;q21), nuclear expression of BCL10 or NF-kB appears to be highly associated with lymphoma cell survival independence of H. pylori-mediated stimulations. Antibiotic eradication, however, is the recommended therapy of choice irrespective of genetic findings, and molecular analysis is not required before initiation of therapy. The influence of genetic translocations including t(11;18)(q21;q21) on systemic therapies, however, is less clearly defined. While small series have shown no influence on the outcome for treatment with the anti-CD20 antibody rituximab (R) or treatment with cladribine (2-CdA), conflicting data have been reported for alkylating agents, especially chlorambucil and the combination of R + chlorambucil. None of other genetic changes seen in MALT lymphoma to date has discernible value in routine clinical applications, but recent data suggest that changes in TNFAIP3(A20), KMTD2 and CARD11 might be associated with response to Bruton kinase inhibitors

Clinical relevance of molecular aspects in extranodal marginal zone lymphoma: a critical appraisal.

Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is among the more common types of lymphoma accounting for up to 8% of newly diagnosed lymphoma cases. As opposed to other B-cell lymphomas, however, no predominant genetic hallmark has been defined in MALT lymphoma, but different localizations appear to be affected by different, sometimes distinct changes. Nonetheless, a high proportion of these genetic changes reported in MALT lymphomas dysregulate the pathways leading to NF-kB activation. t(11;18)(q21;q21)/BIRC3::MALT1 appears to be MALT lymphoma specific and is found in 24% of gastric and 40% of pulmonary MALT lymphomas. The translocation is associated with more disseminated disease in gastric MALT lymphoma and is found in a large percentage of patients whose lymphoma is unresponsive to antibiotic eradication of Helicobacter pylori. In addition to t(11;18)(q21;q21), nuclear expression of BCL10 or NF-kB appears to be highly associated with lymphoma cell survival independence of H. pylori-mediated stimulations. Antibiotic eradication, however, is the recommended therapy of choice irrespective of genetic findings, and molecular analysis is not required before initiation of therapy. The influence of genetic translocations including t(11;18)(q21;q21) on systemic therapies, however, is less clearly defined. While small series have shown no influence on the outcome for treatment with the anti-CD20 antibody rituximab (R) or treatment with cladribine (2-CdA), conflicting data have been reported for alkylating agents, especially chlorambucil and the combination of R + chlorambucil. None of other genetic changes seen in MALT lymphoma to date has discernible value in routine clinical applications, but recent data suggest that changes in TNFAIP3(A20), KMTD2 and CARD11 might be associated with response to Bruton kinase inhibitors

BMC Infectious Diseases / Infection with multidrug-resistant Campylobacter coli mimicking recurrence of carcinoid syndrome: a case report of a neuroendocrine tumor patient with repeated diarrhea

Background Campylobacteriosis caused by Gram-negative bacteria of the genus Campylobacter (mainly C. jejuni and C. coli) is one of the most common gastrointestinal zoonotic infections with increased incidence in humans worldwide. The typical symptoms are severe abdominal cramps, diarrhea and sometimes fever. The clinical course of Campylobacter infection is mainly mild and after one week self-limiting, but can take several weeks in some rare cases. However, patients with neuroendocrine tumors in the gastrointestinal tract, a neoplasm of enterochromaffin/neuroendocrine cell origin, can develop severe diarrhea during progression of tumor growth caused by hormonal excess due to the tumor. Both diseases have very similar clinical symptoms and this case report elaborates the differences. So far it is known in the literature that the clinical symptoms of campylobacteriosis can mimic appendicitis or acute colitis of inflammatory bowel disease but a mimicking of recurrence of carcinoid syndrome in a patient with neuroendocrine tumor is not reported. Case presentation A 72-year-old man with already diagnosed and treated metastatic neuroendocrine tumor of the terminal ileum (G1 rated, Ki-67 index 1 %) was again suffering from increasing diarrhea, abdominal cramps and weight lost. These symptoms were similar to the initial symptoms due to the tumor which improved at the time after total resection of the primary in the terminal ileum and regular therapy with long-acting release depot octreotide intramuscularly. As progression/tachyphylaxis in symptomatic patients with carcinoid syndrome undergoing therapy, reassessment of disease and analysis of tumor markers was initiated, and the interval of intramuscular injections was shortened. Radiological findings and tumor marker levels disclosed no evidence of neuroendocrine tumor progression and the symptoms continued. After 4 weeks with symptoms the patient developed additionally fever. Due to impaired renal function and elevated signs of systemic inflammation fluid replacement and empiric antimicrobial therapy were started. At this time-point the first stool cultures were taken which disclosed an infection with C. coli. The empiric antimicrobial therapy was stopped after five days because of multidrug-resistant isolated strain. During the ongoing symptomatic therapy the patient becomes gradually symptom-free 6 weeks later, resulting a total duration of symptoms caused by campylobacteriosis of 13 weeks. Conclusion This case of infection with C. coli mimicking recurrence of carcinoid syndrome suggests that assessment for bacterial gastrointestinal infections should be taken into account also in patients with neuroendocrine tumors who present worsening of their symptoms in spite of initially successful management. The duration of symptoms caused by campylobacteriosis were significantly extended which might be due to gastroenteric dysfunctions/mucosal changes caused by the carcinoid syndrome in this patient.(VLID)511026