The frequency of aggressive subtypes of B‐cell non‐Hodgkin lymphoma (B‐NHL), such as high‐grade B‐cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL‐DH/TH) or Burkitt‐like ...lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV‐associated aggressive B‐NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy‐five HIV‐associated aggressive B‐NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV‐encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell‐of‐origin classification of diffuse large B‐cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV‐negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL‐DH/TH and BL‐like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV‐associated aggressive B‐NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM‐1 expression in BL, have a negative prognostic impact on HIV‐infected individuals.
Background
Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase ...inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763).
Methods
Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard‐dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo‐HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes.
Results
Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo‐HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease‐free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months P = .05 and 28.7 months vs 11.5 months P = .05 for DFS and OS, respectively).
Conclusions
Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.
Outcomes after first disease recurrence in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia are poor. Patients with overt disease recurrence appear to have a worse prognosis compared with those with molecular recurrence.
The deposition and manipulation of human remains in natural caves are well known for the Neolithic of Southern Iberia. The cultural meaning of these practices is however still largely unclear. Cueva ...de los Marmoles (CM, Priego-Córdoba) is one of the most important cave contexts from Southern Spain, which returned a large number of commingled skeletal remains suggesting its funerary use from the Neolithic to the Late Bronze Age. Here we discuss CM from a chronological and cultural perspective based on new radiocarbon, anthropological, and taphonomic analyses. These include the estimation of the minimum number of individuals, the exploration of fragmentation patterns characterizing different skeletal regions, and the macroscopic and microscopic analysis of modifications to the remains of possible anthropic origin. Radiocarbon data point to a funerary use of CM between the 5
th
-2
nd
millennium cal. BCE. MNI estimates reveal the presence of at least 12 individuals (seven adults and five nonadults). The low representation of elements from hands and feet suggests that individuals were placed in the cave while partially decomposed. Anthropic traces on the remains (e.g. fresh fractures, marrow canal modifications, and scraping marks) hint at their intentional fragmentation, cleaning from residual soft tissues, and in some cases reutilization. These practices are well-exemplified by the recovery of one "skull cup" and of two long bones used as tools. These data align with those from other cave contexts from the same geographic region, suggesting the presence, especially during the Neolithic period, of shared ideologies centered on the human body.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of ...exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients.
Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR.
Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells.
Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis.
Introduction
The presence of iron deficiency (ID) in patients with acute heart failure (AHF) is high. There are few studies on the characteristics of these patients and the safety of ferric ...carboxymaltose administration (FCM).
Objective
Study the differences among patients with AHF based on the presence and type of ID as well as the safety of FCM administration in these patients.
Method
The AHF‐ID study is a multicentre, analytical, prospective follow‐up cohort including patients admitted to six Spanish hospitals for AHF. ID was defined as serum ferritin <100 μg/L (group A) or ferritin 100‐299 μg/L with a TSAT <20% (group B). In cases receiving FCM the appearance of adverse events was analysed. Adjusted Cox regression was used to determine the association with 30‐days reattendance for AHF after discharge.
Results
A total of 221 patients were recruited; 191 (86.4%) presented ID, 121 (63.4%) group A and 70 (36.6%) group B. There were scarce differences between the groups analysed. No differences were found in 30‐days reattendance for AHF. FCM was administered to 158 (71.5%) patients, with 8 (5.1%) presenting adverse events, the most frequent being digestive alterations. Treatment was not discontinued in any case.
Conclusions
There are scarce differences between the presence and the type of ID in patients with AHF. The administration of FCM in patients with ID and AHF is safe.
Complete response (CR) is considered an important goal in most hematologic malignancies. However, in multiple myeloma (MM), there is no consensus regarding whether immunofixation (IF)-negative CR, ...IF-positive near-CR (nCR), and partial response (PR) are associated with different survivals. We evaluated the prognostic influence on event-free survival (EFS) and overall survival (OS) of these responses pre- and post-transplantation in newly diagnosed patients with MM.
We analyzed 632 patients from the prospective Grupo Español de Mieloma 2000 protocol who were uniformly treated with vincristine, carmustine, cyclophosphamide, melphalan, and predisone/vincristine, carmustine, adryamcine, and dexamethasone induction followed by high-dose therapy and autologous stem-cell transplantation.
Post-transplantation response markedly influenced outcomes. Patients achieving CR had significantly longer EFS (median, 61 v 40 months; P < 10(-5)) and OS (medians not reached; P = .01) versus patients achieving nCR, who likewise had somewhat better outcomes compared with patients achieving PR (median EFS, 34 months, P = .07 v nCR; median OS, 61 months, P = .04). EFS and OS and influence of response were similar among older (age 65 to 70 years) and younger (age < 65 years) patients. Similar findings were observed with pretransplantation response, with trends toward EFS (P = .1; P = .05) and OS (P = .1; P = .07) benefit in patients achieving CR versus nCR and PR, respectively. Post-transplantation response was markedly influenced by pretransplantation response; improvements in response were associated with prolonged survival.
Quality of response post-transplantation, notably CR, is significantly associated with EFS and OS prolongation in newly diagnosed patients with MM. There were trends toward similar associations with pretransplantation response status.
Background
The impact of coronavirus disease 2019 (COVID‐19) in haematological patients (HP) has not been comprehensively reported.
Methods
We analysed 39 patients with SARS‐CoV‐2 infection and ...haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non‐cancer patients with COVID‐19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome.
Results
The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty‐seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non‐cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID‐19 therapy were not predictors of outcome.
Conclusion
Mortality of COVID‐19 is significantly higher in patients with haematological malignancies compared to non‐cancer patients. The impact of persistent viral shedding must be considered in order to re‐start therapies and maintain infectious control measures.
This study aimed to determine the effectiveness of whole-cell bacterial immunotherapy, i.e. MV140 and autovaccines, in reducing the number ofurinary tract infections (UTIs)in frail elderly patients ...with recurrent UTI (RUTI).
A prospective cohort observational study was performed including 200 frail elderly subjects suffering RUTI, both females and males, between 2016 and 2018. The effectiveness of autovaccines and the polybacterial formulation MV140 (Uromune®), consisting ofwhole-cell heat-inactivated Escherichia coli25%, Klebsiella pneumoniae25%, Proteus vulgaris25% andEnterococcus faecalis25% were evaluated. Subjects initiated a 3-month sublingually daily course with MV140 or autovaccine, either first treatment or a new course if they had been previously vaccinated prior to inclusion in the study. Number of UTIs and quality of life (QoL, SF-36 score) were measured in the different study groups.
The mean age for participants was 82.67 (SD, 7.12) for female and 80.23 (SD, 11.12) for male subjects. In all groups, 12 months following bacterial immunotherapy, the number of UTIs significantly decreased compared to before the treatment with autovaccine or MV140: the rate of reduction ranged between 7- and 40-fold. An increase in QoL scoring was also observed in any study group. When comparing medical interventions, MV140 conferred significantly higher benefit than autovaccines. For previously vaccinated individuals, a new 3-month course with MV140 or autovaccines provided further clinical improvement.
MV140 and autovaccines emerge as valuable immunoprophylaxis for the management of RUTI in the frail elderly, contributing to an improvement in patient’s quality of life. Herein, MV140 has shown to confer a higher effectiveness compared to autovaccines, regardless sex or course of treatment.
We present a case of disulfiram‐induced mania in a patient with both alcohol use disorder (AUD) and psychostimulant use disorder (PUD), without a history of psychosis or mania. This acute ...presentation may be linked to the increased dopamine levels caused by disulfiram metabolism. Our patient developed manic symptoms 10 days after starting disulfiram, prescribed to treat the AUD. It should be noted that the symptoms resolved rapidly after disulfiram cessation during hospitalization. Disulfiram use is an effective treatment for alcohol dependence. However, there are safety concerns associated with it and it requires close monitoring, particularly in patients with a history of mania, psychosis, or psychostimulant use.
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