Burkitt lymphoma with a granulomatous reaction: an M1/Th1-polarised microenvironment is associated with controlled growth and spontaneous regression.

AIMS: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously. METHODS AND RESULTS: All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV)-positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution. CONCLUSIONS: Our data provide an in-vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy.

Myelodysplasia cutis as the presenting sign of chronic myelomonocytic leukaemia.

We describe an unusual case of myelodysplasia cutis in a patient with chronic myelomonocytic leukaemia.

Dysembryoplastic neuroepithelial tumors: A single-institutional series with special reference to glutamine synthetase expression.

Dysembryoplastic neuroepithelial tumors (DNT) is a benign (World Health Organisation, WHO, grade I) glioneuronal tumor and it represent one of the most frequent neoplasm in patient affected by seizures. The epileptic neuronal activity can be determined by abnormal synchronization, excessive glutamate excitation and\or inadequate GABA inhibition. Increasing evidence suggests that the astrocytes might be involved in this process even if neurons play a relevant role. In particular astrocytes promote the clearance of glutamate, a potent excitatory neurotransmitter of the central nervous system. Indeed, elevated concentrations of extracellular glutamate may determine iper-excitability and seizures as well as other neurological disorders. So, astrocytes, converting glutamate into glutamine via the enzyme glutamine synthetase (GS), could play a protective anti-seizures role. In the present study, we analyzed the immunohistochemical expression of GS in 20 DNTs specimens documenting a constant immunoistochemical expression of GS in astrocytes of the lesional tissue and of the cerebral cortex.

Correction: Frequent traces of EBV infection in Hodgkin and non-Hodgkin lymphomas classified as EBV-negative by routine methods: expanding the landscape of EBV-related lymphomas.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Frequent traces of EBV infection in Hodgkin and non-Hodgkin lymphomas classified as EBV-negative by routine methods: expanding the landscape of EBV-related lymphomas.

The Epstein-Barr virus (EBV) is linked to various B-cell lymphomas, including Burkitt lymphoma (BL), classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) at frequencies ranging, by routine techniques, from 5 to 10% of cases in DLBCL to >95% in endemic BL. Using higher-sensitivity methods, we recently detected EBV traces in a few EBV-negative BL cases, possibly suggesting a "hit-and-run" mechanism. Here, we used routine and higher-sensitivity methods (qPCR and ddPCR for conserved EBV genomic regions and miRNAs on microdissected tumor cells; EBNA1 mRNA In situ detection by RNAscope) to assess EBV infection in a larger lymphoma cohort [19 BL, 34 DLBCL, 44 cHL, 50 follicular lymphomas (FL), 10 T-lymphoblastic lymphomas (T-LL), 20 hairy cell leukemias (HCL), 10 mantle cell lymphomas (MCL)], as well as in several lymphoma cell lines (9 cHL and 6 BL). qPCR, ddPCR, and RNAscope consistently documented the presence of multiple EBV nucleic acids in rare tumor cells of several cases EBV-negative by conventional methods that all belonged to lymphoma entities clearly related to EBV (BL, 6/9 cases; cHL, 16/32 cases; DLBCL, 11/30 cases), in contrast to fewer cases (3/47 cases) of FL (where the role of EBV is more elusive) and no cases (0/40) of control lymphomas unrelated to EBV (HCL, T-LL, MCL). Similarly, we revealed traces of EBV infection in 4/5 BL and 6/7 HL cell lines otherwise conventionally classified as EBV negative. Interestingly, additional EBV-positive cases (1 DLBCL, 2 cHL) relapsed as EBV-negative by routine methods while showing EBNA1 expression in rare tumor cells by RNAscope. The relapse specimens were clonally identical to their onset biopsies, indicating that the lymphoma clone can largely loose the EBV genome over time but traces of EBV infection are still detectable by high-sensitivity methods. We suggest EBV may contribute to lymphoma pathogenesis more widely than currently acknowledged.

Tumor microenvironment of Burkitt lymphoma: different immune signatures with different clinical behavior.

ABSTRACT: Burkitt lymphoma (BL) is characterized by a tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of Epstein-Barr virus-positive (EBV+) BL with granulomatous reaction compared with 8 cases of EBV+ BL and 8 EBV-negative (EBV-) BL, both with typical starry sky pattern, by Gene expression profiling performed on the NanoString nCounter platform. Subsequently, the data were validated using multiplex and combined immunostaining. Based on unsupervised clustering of differentially expressed genes, BL samples formed 3 distinct clusters differentially enriched in BL with a diffuse granulomatous reaction (cluster 1), EBV+ BL with typical starry sky pattern (cluster 2), EBV- BL with typical "starry sky" (cluster 3). We observed variations in the immune response signature among BL with granulomatous reaction and BL with typical "starry sky," both EBV+ and EBV-. The TME signature in BL with diffuse granulomatous reaction showed a proinflammatory response, whereas BLs with "starry sky" were characterized by upregulation of M2 polarization and protumor response. Moreover, the analysis of additional signatures revealed an upregulation of the dark zone signature and epigenetic signature in BL with a typical starry sky. Tumor-associated macrophages and epigenetic regulators may be promising targets for additional therapies for BL lymphoma, opening novel immunotherapeutic strategies.

Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOSSMARCB1-, which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOSSMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOSSmarcb1-. In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOSSMARCB1- within the TME.

Primary Intracerebral Alveolar Soft Part Sarcoma: Report of a Case and Review of the Literature.

Alveolar soft part sarcomas (ASPSs) are rare malignant tumors representing ∼1% of all soft tissue sarcomas. Most ASPS occurring in the central nervous system are metastases. In contrast, primary intracranial ASPSs are extremely rare and only 8 cases have been previously reported in English literature. Here, we report a case of primary alveolar soft part sarcoma in a 16-year-old female patient with no evidence of primary extracranial tumors. Histologically this case fulfilled the criteria of ASPS, and a molecular confirmation has been archived. To date, only 9 primary intracranial ASPS cases, including ours, have been reported in the literature. This report highlights the clinical and pathological characteristics, differential diagnosis, and molecular analysis of primary ASPS of the central nervous system.

Xanthomatous Inflammatory Infiltrate Involving the Spleen: An Unusual Presentation of Erdheim-Chester Disease and Review of the Literature.

BACKGROUND Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by foamy histiocytes, Touton-like giant cells, and fibrosis, typically affecting the diaphyseal and metaphyseal region of the long bones but that can involve any organ or tissue. ECD is usually associated with the BRAF V600E mutation or with other molecular mutations inserted in the MAPK cascade. CASE REPORT We present the case of a 63-year-old man with a previous history of myocardial infarction who underwent an emergency splenectomy for splenic rupture after an accidental fall. Histological examination of the spleen showed a diffuse xanthogranulomatous proliferation (CD68+, CD163+, S100-, CD1a-) with rare Touton-like giant cells in the red pulp. Based on the histologic findings, a diagnosis of ECD was made. However, skeletal involvement and BRAF V600E mutation were not detected. CONCLUSIONS Cases of non-Langerhans cell histiocytosis that are histologically consistent with ECD in unusual sites have been increasingly described. There is also anecdotal evidence for cases being associated with mutations besides BRAF V600E or with no genetic alteration and no skeletal involvement. Likewise, the spectrum of clinical and molecular features of ECD can be broader than previously considered. Furthermore, there is evidence that various phases of the disease can show different clinical presentations with distinct prognostic impact, according to the mutational spectrum. Recognizing ECD at an early stage allows more effective patient management, and pathologists and clinicians should be aware of the unusual clinical presentations of this rare condition.

Distinct pattern of lymphoid neoplasms characterizations according to the WHO classification (2016) and prevalence of associated Epstein-Barr virus infection in Nigeria population.

BACKGROUND: The present study aimed to classify lymphoid neoplasms according to the latest World Health Organization (WHO) classification and outlining the distribution in Nigeria of different entities. Additionally, the study describes the prevalence of lymphoid neoplasms associated with Epstein-Barr virus (EBV) infection in the Nigerian population. METHODS: We collected 152 formalin-fixed paraffin-embedded (FFPE) tissues diagnosed as lymphoma from 2008 to 2018, coming from three different institutions located within three geopolitical zone in Nigeria. These institutions included the University College Hospital (UCH), Ibadan, Oyo State, the Enugu State University of Science and Technology Teaching Hospital (ESUTH), Enugu, Enugu State, and the Meena Histopathology and Cytology Laboratory (MHCL), Jos, Plateau State. RESULTS: From the total 152 cases retrieved, 50 were excluded due to insufficient tissue materials or inconclusive antigen reactivity. We confirmed 66 (64.7%) cases as lymphomas out of the remaining 102 FFPE with a male to female ratio of 2:1 and a mean age of 44.4 years. Ten entities were identified, and of these, chronic lymphocytic leukemia (CLL) was the most prevalent category (34.8%). For the diffuse large B-cell lymphomas not otherwise specified (DLBCL, NOS), the germinal centre B-cell type was the most common (71.4%). Ten lymphoma cases (15.2%) were positive for Epstein-Barr virus (EBV), most of which were Hodgkin lymphoma (HL). CLL was common in the Hausa ethnic group, HL in the Yoruba ethnic group, while the Igbo ethnic group had an equal distribution of CLL, HL, and DLBCL diagnosis. CONCLUSION: Although the distribution of lymphomas in Nigeria shares some similarities with those of other countries, we described distinct features of some subtypes of lymphomas. Also, the study underscores the need for a more precise diagnosis and classification of lymphoid neoplasms in Nigeria using the latest WHO classification.

IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications.

The precise B cell of origin and molecular pathogenesis of nodal marginal zone lymphoma (NMZL) remain poorly defined. To date, due to the rarity of NMZL, the vast majority of already-published studies have been conducted on a limited number of samples and the technical approach to analyze the immunoglobulin genes was of amplifying rearranged variable region genes with the classical direct sequencing of the PCR products followed by cloning. Here, we studied the B cell Ig heavy-chain repertoires by next-generation sequencing (NGS) in 30 NMZL cases. Most of the cases were mutated (20/28; 71.5%) with homologies to the respective germ line genes ranging from 85 to 97, 83%, whereas 8/28 (28.5%) were unmutated. In addition, our results show that NMZL cases have a biased usage of specific immunoglobulin heavy-chain variable (IGHV) region genes. Moreover, we documented intraclonal diversity in all (100%) of the mutated cases and ongoing somatic hypermutations (SHM) have been confirmed by hundreds of reads. We analyzed the mutational pattern to detect and quantify antigen selection pressure and we found a positive selection in 4 cases, whereas in the remaining cases there was an unspecific stimulation. Finally, the disease-specific survival and the progression-free survival were significantly different between cases with mutated and unmutated IGHV genes, pointing out mutational status as a possible new biomarker in NMZL.

Correction to: IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications.

This error was caused due to the author's oversight and this does not change the views or the results presented in the manuscript.

Mesothelial/monocytic incidental cardiac excrescences (MICE): report of a case and review of literature with focus on pathogenesis.

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a benign lesion composed of histiocytes and mesothelial cells, usually found during cardiac surgery. To date, no more than 50 cases are reported in literature, and pathogenesis is still unclear even if different theories have been proposed. Here we report a case of MICE encountered during aortic valve replacement with typical histological features and extensive immunohistochemical investigation. To date, little information is available about the pathogenesis of MICE. We review the current literature focusing on the role of adhesion molecules such as CD31.

NRASQ61K mutated diffuse leptomeningeal melanomatosis in an adult patient with a brief review of the so-called "forme fruste" of neurocutaneous melanosis.

Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38 years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRASQ61K mutation without features of neurocutaneous melanosis.

Enhancing quality control and performance monitoring in thoracic aortic surgery: a 10-year single institutional experience.

OBJECTIVES: The aim of the present study was to monitor performance and learning effects for thoracic aortic surgery. In addition, we evaluated the volume-outcome relationship of patients undergoing surgery of the thoracic aorta, comparing the results of two higher-volume surgeons (HVSs) with six lower volume surgeons. METHODS: A total of 867 thoracic aortic procedures (elective cases n = 753 and Type A acute dissection n = 114) were performed from 2003 to 2013 by eight surgeons (range 28-238 procedures) at our institution. Departmental and individual performance was monitored using control charts, with a predetermined acceptable failure rate of 10%. Perioperative death or one or more of four adverse events constituted failure. Moreover, results of two higher-volume operators (n = 460; 53%) were compared with those of six lower-volume operators (n = 407; 47%). RESULTS: The incidence rate of in-hospital mortality for elective cases was 2% and for Type A dissection repair 9.6%. Institutional control charts revealed that the surgical process was under control for all the study periods apart from small periods of worse than expected performance which were congruent with new surgeons joining the programme. The predominant surgical failure was reoperation for bleeding. There were differences between surgeons with regard to the learning curves and performance. No significant differences were observed between high- and low-volume surgeons in terms of mortality and morbidity for elective cases. However, high-volume surgeons presented a trend suggesting a higher mortality rate in Type A aortic dissection repair (17.1 vs 6.3%; P = 0.09). CONCLUSIONS: Thoracic aortic surgery can be performed with similar results by high- and low-volume surgeon. Control charts can facilitate learning effects and performance monitoring. Implementation of continuous departmental and individual performance monitoring is practicable.

Minimally invasive right thoracotomy approach for mitral valve surgery in patients with previous sternotomy: a single institution experience with 173 patients.

OBJECTIVE: This study presents a review of our experience with minimally invasive mitral valve surgery (MIMVS) in patients with a previous cardiac procedure performed through a sternotomy over a 10-year period. METHODS: From November 2003 to August 2013, 173 patients (age 61.3 ± 12.4 years) underwent reoperative MIMVS through a right minithoracotomy. Previous operations were coronary artery bypass grafting (n = 49; 28.6%), a mitral valve procedure (n = 120; 70.1%), an aortic valve procedure (n = 32; 18.7%), and other operations (n = 14; 8.1%). The mean euroSCORE was 11.2 ± 3.8. The time to redo surgery was 6.9 ± 4.2 years. RESULTS: Procedures were performed with central aortic cannulation in 55 patients (31.7%) and peripheral cannulation in 118 (68.3%). A transthoracic clamp was used in 58 patients (33.5%), an endoaortic balloon in 72 (41.6%), hypothermic ventricular fibrillation in 23 (13.2%), and beating heart in 20 (11.5%). Mean cardiopulmonary bypass and crossclamp times were 160 ± 58 minutes and 82 ± 49 minutes, respectively. Mitral repair was performed in 53 patients (30.6%). Forty-three patients (24.7%) had an additional cardiac procedure. Conversion to sternotomy was necessary in 2 patients (1.1%) and reoperation for bleeding in 11 patients (6.3%). Thirty-day mortality was 4.1% (n = 7). Major morbidities included stroke (n = 11; 6%) and new-onset dialysis requirement (n = 4; 2.3%). The mean blood transfusion requirement was 1.4 ± 1.1 units. Mean follow-up was 3.3 ± 2.6 years. Survival at 1, 5, and 10 years was 93.1% ± 1.9%, 87.5% ± 2.7%, and 79.7% ± 3.8%, respectively. CONCLUSIONS: Reoperative mitral valve surgery can be safely performed through a right minithoracotomy with good early and late outcomes. The avoidance of extensive surgical dissection, optimal valve exposure, and low blood transfusion are the main advantages of this technique.

Training surgeons in minimally invasive mitral valve repair: a single institution experience.

BACKGROUND: We aimed to study the results of minimally invasive mitral valve repair performed by 5 young surgeons who were trained in mitral valve repair directly through a minimally invasive approach, and a senior surgeon who introduced the technique at our institution and was responsible for the training program. METHODS: This was a retrospective, observational cohort study of prospectively collected data from 595 consecutive patients who underwent minimally invasive mitral repair performed by 5 trainees (n = 240, 40.3%) and by our lead consultant (n = 355, 59.7%) between 2007 and 2013. Treatment selection bias was controlled by constructing a propensity score from core patient characteristics and it was included along with the comparison variable in the multivariable analyses of outcome. RESULTS: Patients operated on by trainees were more likely to be female (p = 0.04), older (p = 0.001), and with history of atrial fibrillation (p = 0.001). Trainees required a significant longer cardiopulmonary bypass (137 ± 56 vs 123 ± 52 minutes; p = 0.003) and aortic clamp time (97 ± 41 vs 83 ± 40 minutes; p = 0.001). I-hospital mortalities were 1.3% in the trainees group and 0.8% in the senior surgeon group (p = 0.6). The incidence of stroke (1.7% vs 2.5%; p = 0.5), conversion to sternotomy (2.6% vs 3.5%; p = 0.5), and conversion to mitral valve replacement (12.5% vs 10.9%; p = 0.6) were similar between groups. No differences were found regarding other complications. Five-year survival (88.9% vs 89.5%; p = 0.4) and freedom from reoperation (94.5% vs 95.1; p = 0.6) were similar between groups. CONCLUSIONS: Minimally invasive mitral valve repair is a safe and reproducible surgical technique that can be taught successfully to cardiac trainees.

Triple valve surgery in the modern era: short- and long-term results from a single centre.

OBJECTIVES: Triple valve surgery (TVS) is still a challenge for surgeons because of prolonged cardiopulmonary bypass (CPB) and myocardial ischaemic times. The reported operative mortality rate for TVS ranges between 2.5 and 25%; long-term survival is also diminished, with reported survival rates at 5 and 10 years of 75-82 and 61-75%, respectively. The objective of our study is to define early and late clinical outcomes, reporting the initial experience in the treatment of triple valve disease through a minimally invasive approach. METHODS: A retrospective, observational, cohort study was undertaken of prospectively collected data on 106 patients who underwent TVS at our institution between October 2001 and June 2013. A total of 101 procedures were done through the standard median sternotomy; however, in 5 patients, the surgical procedure was carried out through a right minithoracotomy. Univariate analysis was performed to identify predictors of early and late survival. RESULTS: The in-hospital mortality rate was 5.6% (6 of 107 patients). Predictors of early mortality were: previous cardiac surgery [odds ratio (OR) 4, 95% confidence interval (CI) 1.08-5.2, P = 0.04], preoperative left ventricular ejection fraction (LVEF) (OR 0.9, 95% CI 0.8-1.1, P = 0.003), prolonged CPB time (OR 1.02, 95% CI 1.01-1.04, P = 0.01) and postoperative pulmonary complications (OR 8, 95% CI 5.8-41, P = 0.0001). Five- and 10-year survival rates were 85 ± 3 and 65 ± 9%, respectively. In univariate analysis, diabetes [hazard ratio (HR) 2.5, 95% CI 1-6.2, P = 0.045], preoperative dialysis (HR 3, 95% CI 2-4.7, P = 0.001), unstable angina (HR 4.8, 95% CI 1-18, P = 0.03), preoperative LVEF (HR 0.9, 95% CI 0.8-1.1, P = 0.02), concomitant coronary artery bypass grafting (CABG) (HR 2.5, 95% CI 1.5-5.7, P = 0.006), prolonged CPB time (HR 1.02, 95% CI 1.01-1.13, P = 0.006), postoperative pacemaker (PMK) implantation (HR 6.2, 95% CI 1.3-18, P = 0.01) and postoperative pulmonary complications (HR 3.3, 95% CI 2.1-7.3, P = 0.002) were found to be significant predictors of late mortality following TVS. The freedom rates from valve-related complications and reoperation at 10 years were 95 ± 2 and 97 ± 2%, respectively. The 10-year freedom rates from thromboembolism and anticoagulation-related haemorrhage were 88 ± 5 and 88 ± 4%, respectively. CONCLUSIONS: TVS offers encouraging short-term and long-term patient survival; these good results after TVS in patients with advanced valvular heart disease justify aggressive surgical therapy in these patients. TVS with a minimally invasive approach is feasible and could be another treatment option.

Mitral valve repair versus replacement in patients with ischaemic mitral regurgitation and depressed ejection fraction: risk factors for early and mid-term mortality†.

OBJECTIVES: Mitral valve (MV) surgery for ischaemic mitral regurgitation (IMR) in patients with depressed left ventricular ejection fraction (LVEF) is associated with poor outcomes. The optimal surgical strategy for IMR in these patients remains controversial. The objective of this study was to compare the early mortality and mid-term survival of MV repair versus MV replacement in patients with IMR and depressed LVEF undergoing coronary artery bypass grafting (CABG). METHODS: A retrospective, observational, cohort study was undertaken of prospectively collected data on 126 consecutive CABG patients with IMR and LVEF <40% undergoing either MV repair (n = 98, 78%) or MV replacement (n = 28, 22%) between July 2002 and February 2011. RESULTS: The overall mortality rate was 7.9% (n = 10). MV replacement was associated with a 4-fold increase in the risk of death compared with MV repair [17.9%, n = 5 vs 5.1%, n = 5; odds ratio (OR) 4.04, 95% confidence interval (CI) 1.08-15.1, P = 0.04]. However, after adjusting for preoperative risk factors, the type of surgical procedure was not an independent risk factor for early mortality (OR 0.1, 95% CI 0.01-31, P = 0.7). Multivariable analysis showed that preoperative LVEF (OR 0.8, 95% CI 0.6-0.9, P = 0.018), preoperative B-type natriuretic peptide (BNP) levels (OR 1.01, 95% CI 1-1.02, P = 0.025), preoperative left ventricle end-systolic diameter (OR 0.8, 95% CI 0.7-1.0, P = 0.05) and preoperative left atrial diameter (OR 1.3, 95% CI 1.0-1.6, P = 0.015) were independent risk factors of early mortality. At the median follow-up of 45 months (interquartile range 20-68 months), the mid-term survival rate was 74% in the MV repair group and 70% in the MV replacement group (P = 0.08). At follow-up, predictors of worse survival were BNP levels [hazard ratio (HR) 1.0, 95% CI 1.0-1.01, P = 0.047], preoperative renal failure (HR 4.6, 95% CI 1.1-20.3, P = 0.039) and preoperative atrial fibrillation (HR 3.3, 95% CI 1.1-10, P = 0.032). CONCLUSIONS: MV repair in CABG patients with IMR and depressed LVEF is not superior to MV replacement with regard to operative early mortality and mid-term survival.