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Abstract Background Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients. Methods We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators. We assessed progression-free survival (PFS) and overall survival (OS), and focused on identifying risk factors. Results The cohort included 42% of patients (n = 71) with 0 HRCA, 42% (n = 71) with 1 HRCA, and 16% (n = 26) with ≥ 2 HRCA. After a median follow-up of 31 months, the median PFS was 53 months (95% CI, 37–69), and OS was not reached for the entire cohort. Despite similar rates of MRD-negativity post-ASCT, patients with ≥ 2 HRCA, termed “double hit” (DH), had a significantly higher risk of progression/mortality than those with 0 or 1 HRCA. Multivariate analysis highlighted DH (HR 4.103, 95% CI, 2.046–8.231) and MRD positivity post-ASCT (HR 6.557, 95% CI, 3.217–13.366) as adverse prognostic factors for PFS, with DH also linked to inferior OS. As anticipated, DH patients with post-ASCT MRD positivity displayed the poorest prognosis, with a median PFS of 7 months post-ASCT. Meanwhile, DH patients with MRD negativity post-ASCT showed improved prognosis, akin to MRD-negative non-DH patients. It is noteworthy to exercise caution, as DH patients who initially achieved MRD negativity experienced a 41% cumulative loss of that status within one year. Conclusions This study strongly advocates integrating DH genetic assessments for eligible ASCT patients and emphasizes the importance of ongoing MRD monitoring, as well as considering MRD-based treatment adaptation for those patients in real-world settings.

Background: Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients. Methods: We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators. We assessed progression-free survival (PFS) and overall survival (OS), and focused on identifying risk factors. Results: The cohort included 42% of patients (n = 71) with 0 HRCA, 42% (n = 71) with 1 HRCA, and 16% (n = 26) with ≥ 2 HRCA. After a median follow-up of 31 months, the median PFS was 53 months (95% CI, 37–69), and OS was not reached for the entire cohort. Despite similar rates of MRD-negativity post-ASCT, patients with ≥ 2 HRCA, termed "double hit" (DH), had a significantly higher risk of progression/mortality than those with 0 or 1 HRCA. Multivariate analysis highlighted DH (HR 4.103, 95% CI, 2.046–8.231) and MRD positivity post-ASCT (HR 6.557, 95% CI, 3.217–13.366) as adverse prognostic factors for PFS, with DH also linked to inferior OS. As anticipated, DH patients with post-ASCT MRD positivity displayed the poorest prognosis, with a median PFS of 7 months post-ASCT. Meanwhile, DH patients with MRD negativity post-ASCT showed improved prognosis, akin to MRD-negative non-DH patients. It is noteworthy to exercise caution, as DH patients who initially achieved MRD negativity experienced a 41% cumulative loss of that status within one year. Conclusions: This study strongly advocates integrating DH genetic assessments for eligible ASCT patients and emphasizes the importance of ongoing MRD monitoring, as well as considering MRD-based treatment adaptation for those patients in real-world settings. [ABSTRACT FROM AUTHOR]

Nearly a billion people worldwide are infected with the hepatitis B Virus (HBV) and about a third of them have chronic infection. HBV is an important cause of morbidity and mortality, including acute and chronic hepatitis and hepatocellular carcinoma (HCC). Screening and control of primary HBV infection through vaccination represent a major advance in global public health, but large sections of the world population, in both developed and underdeveloped countries, remain unscreened and unvaccinated. In addition to being a global cause of liver disease, an important role of HBV in lymphoma has also emerged. First, the high risk of HBV reactivation in previously infected patients receiving chemo-immunotherapy necessitates the systematic evaluation of HBV serological status in all non-Hodgkin's lymphoma (NHL) cases and preemptive antiviral therapy for those who may have chronic or occult HBV infection. Second, HBV has been shown to infect lymphocytes, namely B-cells, and has been associated with a higher risk of developing B-cell lymphoma, most clearly in countries where HBV is endemic. While the risk of HBV reactivation with chemoimmunotherapy in NHL is well known, the role and the impact of HBV as a global lymphoma risk factor and potential oncogenic driver in B-cells are very poorly understood. Here, we review the clinical and scientific evidence supporting an association between HBV and B-cell lymphoma, with a particular focus on diffuse large B-cell lymphoma (DLBCL) and provide an overview of the estimated impact of HBV infection on the biology and clinical course of DLBCL. We also discuss ways to gain a better insight into the unmet need posed by HBV in lymphoma and whether assessing immune responses to HBV, measuring viral loads, and detecting the presence of HBV-encoded proteins in tumor tissue could be integrated into the molecular and clinical risk stratification of patients with DLBCL. [ABSTRACT FROM AUTHOR]

Simple Summary: Double/triple-hit lymphomas (DHLs/THLs) are an aggressive type of high-grade B-cell lymphomas (HGBLs), characterized by translocations in MYC and BCL2/BCL6. DHL patients respond poorly to standard chemoimmunotherapy regimens; thus, timely and accurate diagnosis is of paramount importance for their proper clinical management. The standard technique used for the identification of these translocations is fluorescence in situ hybridization (FISH), which is not routinely performed at every medical center to all potential patients. In the current study, we employed an image-based, artificial intelligence, deep learning algorithmic tool for the identification of DHL/THL cases by analyzing scanned histopathological H&E-stained tissue slide images. Our preliminary results demonstrate high performances, suggesting the potential use of such a solution in the clinical workflow to support the management of HGBL patients. Deep learning applications are emerging as promising new tools that can support the diagnosis and classification of different cancer types. While such solutions hold great potential for hematological malignancies, there have been limited studies describing the use of such applications in this field. The rapid diagnosis of double/triple-hit lymphomas (DHLs/THLs) involving MYC, BCL2 and/or BCL6 rearrangements is obligatory for optimal patient care. Here, we present a novel deep learning tool for diagnosing DHLs/THLs directly from scanned images of biopsy slides. A total of 57 biopsies, including 32 in a training set (including five DH lymphoma cases) and 25 in a validation set (including 10 DH/TH cases), were included. The DHL-classifier demonstrated a sensitivity of 100%, a specificity of 87% and an AUC of 0.95, with only two false positive cases, compared to FISH. The DHL-classifier showed a 92% predictive value as a screening tool for performing conventional FISH analysis, over-performing currently used criteria. The work presented here provides the proof of concept for the potential use of an AI tool for the identification of DH/TH events. However, more extensive follow-up studies are required to assess the robustness of this tool and achieve high performances in a diverse population. [ABSTRACT FROM AUTHOR]

Abstract Background Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia—the most common risk factor in humans—and analyze the additional effect of ventilator-induced lung injury (VILI). Methods Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2

Nearly a billion people worldwide are infected with the hepatitis B Virus (HBV) and about a third of them have chronic infection. HBV is an important cause of morbidity and mortality, including acute and chronic hepatitis and hepatocellular carcinoma (HCC). Screening and control of primary HBV infection through vaccination represent a major advance in global public health, but large sections of the world population, in both developed and underdeveloped countries, remain unscreened and unvaccinated. In addition to being a global cause of liver disease, an important role of HBV in lymphoma has also emerged. First, the high risk of HBV reactivation in previously infected patients receiving chemo-immunotherapy necessitates the systematic evaluation of HBV serological status in all non-Hodgkin’s lymphoma (NHL) cases and preemptive antiviral therapy for those who may have chronic or occult HBV infection. Second, HBV has been shown to infect lymphocytes, namely B-cells, and has been associated with a higher risk of developing B-cell lymphoma, most clearly in countries where HBV is endemic. While the risk of HBV reactivation with chemoimmunotherapy in NHL is well known, the role and the impact of HBV as a global lymphoma risk factor and potential oncogenic driver in B-cells are very poorly understood. Here, we review the clinical and scientific evidence supporting an association between HBV and B-cell lymphoma, with a particular focus on diffuse large B-cell lymphoma (DLBCL) and provide an overview of the estimated impact of HBV infection on the biology and clinical course of DLBCL. We also discuss ways to gain a better insight into the unmet need posed by HBV in lymphoma and whether assessing immune responses to HBV, measuring viral loads, and detecting the presence of HBV-encoded proteins in tumor tissue could be integrated into the molecular and clinical risk stratification of patients with DLBCL.

Background: Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia—the most common risk factor in humans—and analyze the additional effect of ventilator-induced lung injury (VILI). Methods: Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2 < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed. Results: All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO2/FiO2 was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage. Conclusions: In conclusion, we established an accurate pulmonary sepsis-induced ARDS model. [ABSTRACT FROM AUTHOR]

Objectives: To explore the combined effect of pediatric sickle cell disease (SCD) and preterm birth on cognitive functioning. Methods: Cognitive functioning was examined in children ages 6–8 with high risk SCD genotypes born preterm (n = 20) and full-term (n = 59) and lower risk SCD genotypes/no SCD born preterm (n = 11) and full-term (n = 99) using tests previously shown to be sensitive to SCD-related neurocognitive deficits. Factorial ANOVAs and log linear analyses were conducted to examine the relationship between SCD risk, preterm birth status, and cognitive outcomes. Continuous scores were examined for specific tests. Children were categorized as having an abnormal screening outcome if at least one cognitive score was ≥1.5 standard deviations below the population mean. Results: Children with elevated risk due to high risk SCD and preterm birth performed worse than other groups on a test of expressive language but not on tests that emphasize processing speed and working memory. There was a three-way interaction between preterm status, SCD risk, and abnormal screening outcome, which was largely driven by the increased likelihood of abnormal cognitive scores for children with high risk SCD born preterm. Conclusions: The combination of SCD and preterm birth may confer increased risk for language deficits and elevated rates of abnormal cognitive screenings. This suggests that neurodevelopmental risk imparted by comorbid SCD and preterm birth may manifest as heterogenous, rather than specific, patterns of cognitive deficits. Future studies are needed to clarify the domains of cognitive functioning most susceptible to disease-related effects of comorbid SCD and preterm birth. [ABSTRACT FROM AUTHOR]

Genetic and environmental models of neuropsychiatric disease have grown exponentially over the last 20years. One measure that is often used to evaluate the translational relevance of these models to human neuropsychiatric disease is prepulse inhibition of startle (PPI), an operational measure of sensorimotor gating. Deficient PPI characterizes several neuropsychiatric disorders but has been most extensively studied in schizophrenia. It has become a useful tool in translational neuropharmacological and molecular genetics studies because it can be measured across species using almost the same experimental parameters. Although initial studies of PPI in rodents were pharmacological because of the robust predictive validity of PPI for antipsychotic efficacy, more recently, PPI has become standard common behavioral measures used in genetic and neurodevelopmental models of schizophrenia. Here we review "two hit" models of schizophrenia and discuss the utility of PPI as a tool in phenotyping these models of relevant risk factors. In the review, we consider approaches to rodent models of genetic and neurodevelopmental risk factors and selectively review "two hit" models of gene×environment and environment×environment interactions in which PPI has been measured.

Background: Large B cell lymphoma (LBCL) is the most common form of lymphoma. Polatuzumab vedotin (polatuzumab) is an effective therapy for patients diagnosed with LBCL; however, only limited information regarding pathologic features detected by clinical laboratory assays is available to determine which patients are most likely to benefit from polatuzumab based therapies., Patients and Methods: We collected data from real world patients with relapsed or refractory LBCL whose tumors underwent next generation sequencing and were treated with polatuzumab based therapy at a single large academic cancer center. Tumor and patient characteristics were analyzed to look for factors that predict response to polatuzumab based therapies., Results: We identified high grade B cell lymphoma (HGBL) -NOS or MYC/BCL2 histology and presence of MYC rearrangement as factors that predict inferior response to polatuzumab based therapy. Patients with germinal center B cell of origin (GCB COO) LBCL without these factors had a high response rate (73%) to polatuzumab based therapy., Conclusion: In a single center real world retrospective analysis of R/R LBCL patients with available genomic data, polatuzumab based therapy may be less effective in patients with HGBL-NOS or MYC/BCL2 histology and MYC rearrangements, but not in patients with GCB COO LBCL without these features. Routine performance of more comprehensive pathologic analysis of tumors may inform the use of polatuzumab based therapy in patients with LBCL., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The pathophysiology behind negative and cognitive symptoms of schizophrenia is not well understood, thus limiting the effectiveness of treatment on these symptoms. Developing reliable animal model of schizophrenia is vital to advance our understanding on the neurobiological basis of the disorder. Double hit is used to refer to the use of two schizophrenia inducing interventions viz ketamine exposure and social isolation. In this study we aim to investigate the robustness of double hit model of schizophrenia in inducing negative and cognitive symptoms of schizophrenia. On postnatal day (PND) 23, thirty-two male Sprague Dawley rats were randomly grouped into four equal groups as follows: group housed + saline (GH), group housed + ketamine (GHK), isolated + saline (SI), and isolated + ketamine (SIK). A single ketamine dose (16 mg/kg) was administered 3 times a week for four weeks. Isolated animals were housed singly throughout the study. The following behavioural tests were carried out: elevated plus maze, three chamber social interaction, resident intruder tests, and novel object recognition (NOR). The SIK group exhibited high anxiety levels, with increased ACTH, corticosterone and norepinephrine concentration when compared to the other groups. The SIK animals also presented with reduced social interaction and decreased oxytocin concentration. SIK rats were more aggressive towards a juvenile intruder but had low testosterone concentration. The SIK group or double hit model showed impaired visual learning and memory and increased expression of proinflammatory cytokines. This suggest that the double hit model is more robust in inducing negative and cognitive symptoms of schizophrenia than each treatment alone., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: It is unknown whether Epstein–Barr virus (EBV) infection can occur in high‐grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, also known as double‐ or triple‐hit lymphoma (DHL/THL). Methods and results: Here we report 16 cases of EBV+ DHL/THL from screening 846 cases of DHL/THL and obtaining additional EBV+ cases through multi‐institutional collaboration: eight MYC and BCL2 DHL, six MYC and BCL6 DHL and two THL. There were eight men and eight women, with a median age of 65 years (range = 32–86). Two patients had a history of follicular lymphoma and one had AIDS. Nine of 14 patients had an International Prognostic Index of ≥3. Half of the cases showed high‐grade/Burkitt‐like morphology and the other half diffuse large B cell lymphoma morphology. Using immunohistochemistry, the lymphoma cells were positive for MYC (n = 14 of 16), BCL2 (n = 12 of 16), BCL6 (n = 14 of 16), CD10 (n = 13 of 16) and MUM1 (n = six of 14). Using Hans' algorithm, 13 cases were classified as germinal centre B cell (GCB) and three as non‐GCB. The lymphomas frequently showed an EBV latency Type I with a median EBV‐encoded small RNAs of 80% positive cells (range = 20–100%). After a median follow‐up of 36.3 months (range = 2.0–41.6), seven patients died, with a median survival of 15.4 months (range = 3.4–47.3) after diagnosis of EBV+ DHL/THL. Five of six patients with MYC and BCL6 DHL were alive, including four in complete remission. In contrast, only four of 10 patients with MYC and BCL2 DHL or THL were alive, including two in complete remission. The median survival in patients with MYC and BCL6 DHL was unreached and was 21.6 months in patients with MYC and BCL2 DHL or THL. Conclusions: EBV infection in DHL/THL is rare (~1.5%). Cases of EBV+ DHL/THL are largely similar to their EBV– counterparts clinicopathologically. Our findings expand the spectrum of EBV+ B cell lymphomas currently recognised in the World Health Organisation classification and suggest differences between EBV+MYC and BCL2 DHL versus EBV+MYC and BCL6 DHL that may have therapeutic implications. [ABSTRACT FROM AUTHOR]

We retrospectively studied the impact of cytogenetic abnormalities in 328 consecutive newly diagnosed multiple myeloma (MM) patients. High-risk cytogenetic abnormalities (HRCAs) included del (17p), amp/gain (1q21), t(4;14), and t(14;16). We defined a standard-risk group by the absence of HRCA, an intermediate-risk group with one HRCA, and a high-risk (HiR) group with at least two HRCAs. The HiR group constituted 14.3% of patients and was associated with a median overall survival (OS) of 28.6 months and progression-free survival (PFS) of 14.0 months. Moreover, the HiR group predicted poor outcomes for OS and PFS in multivariate analyses, and bortezomib prolongation to nine cycles could not bring additional benefit to this entity, suggesting the necessity of more effective therapies for these patients. Furthermore, we confirmed the independent prognostic impact of amp 1q21 in this real-world study. [ABSTRACT FROM AUTHOR]

Double-hit lymphoma (DHL) is a unique subtype of non-Hodgkin lymphoma characterized by atleast two rearrangements involving MYC, BLC2, and/or BCL6. These lymphomas are uncommon and aggressive, responding poorly to typical chemotherapy regimens. Lymphomas rarely arise from the oral cavity or tonsils, and those presenting as a neck mass are predominantly diffuse large B-cell lymphoma. To date, primary DHL of the tonsils has yet to be described in the literature. Here, we report a case of a 44 year-old male patient with well-controlled human immunodeficiency virus (HIV) who presented with a sore throat. He subsequently developed acute respiratory compromise due to a rapidly enlarging tonsillar mass. Pathologic and genetic analysis confirmed the presence of BCL6 and MYC rearrangements suggestive of DHL of the tonsils. In a young patient with HIV and a neck mass, it is essential that lymphoma remains on the list of differential diagnoses as prompt diagnosis and treatment may prevent complications from its rapid expansion. [ABSTRACT FROM AUTHOR]

High-grade B cell lymphomas with rearrangements on C-MYC and BCL2 and/or BCL6 (HGBL with MYC and BCL2 and/or Bcl6 rearrangement) are associated with worse clinical outcomes and thus were introduced as a separate new category in the recently updated WHO classification. From 2012 to 2016, we analyzed a consecutive cohort of large B cell lymphomas (LBCLs) for C-MYC, BCL2, and BCL6 rearrangements and correlated our results with clinical-pathological parameters. Ten of 78 (13%) cases had a C-MYC and BCL2 and/or BCL6 rearrangement, so-called double or triple hit (DH), while double/triple copy number gains (CNGs) were found in eight (10%) patients. Patients with a high-grade lymphoma with DH or CNG progressed significantly more often after first-line chemotherapy (p = 0.005). When treated with standard chemotherapy, patients with a DH or CNG had a significantly worse overall (OS) and recurrence free survival (RFS) compared with all other patients (p = 0.033 and p < 0.001, respectively). Thus, patients with a diffuse large B cell lymphoma, harboring a double/triple CNG, seem to have a similar poor prognosis than those with a DH. Though our data can only be regarded as preliminary, our results warrant further investigations to fully elucidate the role of CNGs as well as underlying molecular mechanisms resulting in aggressive behavior in LBCL. [ABSTRACT FROM AUTHOR]

Objectives: To better characterize the clinicopathologic presentation and outcomes of follicular lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit and triple-hit follicular lymphoma), we present three cases from our institution and perform a literature review of 37 published cases.Methods: Cases were identified using institutional SoftPath software and the MEDLINE database via the PubMed search engine. Clinical and pathologic data were collected with subsequent stratification by histologic grade and treatment for comparison.Results: Similar to classic follicular lymphoma, patients presented most often with low-grade (1-2) but high-stage (III-IV) disease with absence of B symptoms; however, overall survival was worse than that of traditional follicular lymphoma. In a small sample size, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) achieved better outcomes than a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Specific pathologic features that might prompt testing for MYC rearrangement include elevated proliferation index out of proportion to cytology and aggressive features such as angioinvasion.Conclusions: Double-hit and triple-hit follicular lymphoma may be better classified as a distinct entity from classical follicular lymphoma with a worse prognosis. Aggressive therapy with a treatment regimen used for high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements might be beneficial, but more evidence is needed to justify aggressive treatment as standard of care. [ABSTRACT FROM AUTHOR]

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient. [ABSTRACT FROM AUTHOR]

Background: Sporadic Burkitt lymphoma (BL), characterised by translocation-associated C-MYC upregulation is a rare, aggressive lymphoma with a cure rate up to 90 % using the R-CODOX-M/R-IVAC (RCRI) protocol. RCRI is active in HIV-associated BL in combination with HAART. The WHO classification system defines lymphomas intermediate between DLBCL and BL, in which lymphomas with t(14;18)(q32;q21) and C-MYC-carrying translocation, i.e. 'double-hit' are included (BL-DH), and these patients are conventionally treated with RCRI. Result: We describe the SJH experience of 25 patients with BL, BL + HIV and BL-DH treated with RCRI between 2002 and 2011. Twelve BL patients (8M/4F), median age 49.1 years (range 20-73 years); of whom 9 had extensive disease, including 8 with marrow and 2 with CNS involvement. Eleven patients remain in remission at 80.5 months (range 37-147 months) from completion of treatment and one died of progressive BL giving an OS of 91.6 % at 1 year with no late relapses. Eight patients with BL + HIV were treated (6M/2F) with a median age 40.25 years (range 24-64). Five remain in complete remission (CR) at 65 months (range 13-109 months), three patients died, two of progressive disease and one of treatment-associated hepatotoxicity in CR. Five patients with BL-DH were included; (3M/2F), age 47.8 years (range 42-55 years); and all patients died of progressive disease, 4 on RCRI therapy and a further patient despite an allogeneic transplantation. Conclusion: These results confirm that RCRI is an effective treatment in adults with BL and BL + HIV and remains the gold standard against which other regimens should be compared. We confirm the poor prognosis found in BL-DH, indicating new treatment approaches are needed for this sub-group which should be identified at diagnosis by FISH analysis. [ABSTRACT FROM AUTHOR]

Background Dextranomer/hyaluronic acid (Dx/Ha;Dexell®) and polyacrylate-polyalcohol copolymer (PPC;Vantris®) are the popular tissue-augmenting substances using for the endoscopic injections of vesicoureteral reflux (VUR). The aim of the study is to evaluate and compare Dx/Ha and PPC in terms of effectiveness, injection techniques and complications with special emphasis on vesicoureteral junction obstruction (VUJO). Methods A total of 95 patients who underwent endoscopic VUR treatment between 2009 and 2015 were retrospectively reviewed. The patients were divided into two groups: group 1: Patients underwent endoscopic treatment with PPC (n = 50 patients, 70 renal refluxing units) group 2: Patients underwent endoscopic treatment with Dx/Ha (n = 45 patients, 74 renal refluxing units). Results The overall resolution rates based on the number of renal refluxing units studied was 88.6% and 70.3% in group 1 and group 2, respectively. Resolution rates were significantly better in group 1 compared to group 2. VUJO requiring ureteral reimplantation or stent insertion developed in 7 patients in group 1. No VUJO was observed in group 2. VUJO in group 1 was markedly higher than that in group 2. Conclusions Endoscopic treatment of VUR with PPC promises better resolution rates but higher VUJO rates compared to Dx/Ha. [ABSTRACT FROM AUTHOR]

Objectives: Primary mediastinal large B-cell lymphomas (PMLBCLs) are aggressive lymphomas with characteristic clinical, morphologic, and immunophenotypic features. "Double-hit" (DH) lymphomas are B-cell neoplasms characterized by a translocation involving MYC and either BCL2 or BCL6 In the indexed literature, there are no reported cases of PMLBCL associated with DH or triple-hit events.Methods: Herein, we present a case of a 15-year-old girl with PMLBCL who had typical clinical, morphologic, and immunophenotypic features.Results: Fluorescent in situ hybridization studies showed rearrangements involving MYC and BCL6 We also excluded the possibility of a reciprocal t(3;8) (3q27;8q24) BCL6/MYC translocation.Conclusions: This case expands the current spectrum of lymphomas subtypes in which DH can be found and supports the rationale for cytogenetic testing for DH abnormalities in all cases of aggressive large B-cell lymphomas regardless of subtype. [ABSTRACT FROM AUTHOR]

Burkitt lymphoma is cytogenetically characterized by t(8;14)(q24;q32) translocation, sometimes accompanied by additional cytogenetic abnormalities. These abnormalities usually result in more aggressive clinical presentation and morphology of the disease. The current report presens a case of Burkitt lymphoma with t(8;14)(q24;q32) accompanied by partial tetrasomy of chromosome 1(47,XY,+1,i(1)(q10),t(8;14) (q24;q32)[2]/46,XY[18]). The patient was a 59-year-old male who presented with abdominal pain, leukocytosis and tumor lysis syndrome. No lymphadenopathy was noted. Cerebrospinal fluid analysis revealed atypical lymphocytes. A peripheral blood smear revealed tumor cells exhibiting distinct 'blastoid' morphology: Prominent nucleoli, basophilic cytoplasm, occasional cytoplasmic vacuoles. Flow cytometry demonstrated B cells expressing cluster of differentiation (CD)10 and cytoplasmic kappa light chain restriction without surface expression of immunoglobulins and CD20. A bone marrow biopsy revealed hematopoiesis, with a 90% replacement with atypical lymphocytes. The patient was treated with chemotherapy. Following the first cycle of treatment, the patient developed neutropenic fever, bacteremia and died a few days later. Gain of chromosome 1q in addition to characteristic for Burkitt lymphoma t(8;14)(q24;q32) resulted in immature 'blastoid' morphology and the immunophenotype of tumor cells, leukemic presentation without lymph node involvement and a highly aggressive clinical course. [ABSTRACT FROM AUTHOR]