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1.
J Gastroenterol Hepatol ; 39(5): 935-941, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38267213

RESUMO

BACKGROUND: Collection of bile aspirate during endoscopic retrograde cholangiopancreatography (ERCP) is essential to identify pathogens responsible for acute cholangitis. Limited data are available on the risk factors for the presence of multidrug-resistant organisms (MDRO) in bile. METHODS: We conducted this retrospective, single-center study to assess the prevalence and susceptibility rates of bacteria in bile cultures, and the risk factors for the presence of pathogens, MDRO, and fungi in bile. All consecutive patients who underwent biliary drainage for acute cholangitis from January 2017 to December 2019 were included. RESULTS: 443/1610 ERCPs were performed for acute cholangitis. Bile culture was collected in 91.4% (405/443), of which 86.7% were positive. Most common isolates were Enterococcus faecalis (37.6%) and Escherichia coli (32.8%). Vancomycin resistance was found in 9.9% of Enterococcus species (spp.); extended-spectrum beta-lactamases (ESBL) and carbapenemases in 11.2% and 0.9% of Enterobacteriaceae, respectively. The empiric antimicrobial therapy was changed in 26.4% (n = 107) of cases, with a clinical response in 90.7%. In multivariate analysis, biliary stenting was an independent risk factor for positive bile culture (odds ratio [OR] 9.43; P < 0.01). Independent risk factors for MDRO in bile were patient age>60 years (OR 2.51; P = 0.03), previous sphincterotomy (OR 2.57; P = 0.02), and biliary stenting (OR 2.80; P < 0.01). Previous sphincterotomy was the only risk factor for isolation of fungi in bile (OR 1.61; P = 0.04). CONCLUSIONS: Our study showed an increasing prevalence of Enterococcus spp. and MDRO. Bile cultures should be routinely collected in cholangitis and in patients with repeated ERCPs to allow more efficient antimicrobial treatment.


Assuntos
Bile , Colangiopancreatografia Retrógrada Endoscópica , Colangite , Centros de Atenção Terciária , Humanos , Estudos Retrospectivos , Colangite/microbiologia , Colangite/epidemiologia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Masculino , Doença Aguda , Fatores de Risco , Feminino , Bile/microbiologia , Idoso , Pessoa de Meia-Idade , Farmacorresistência Bacteriana Múltipla , Idoso de 80 Anos ou mais , Escherichia coli/isolamento & purificação , Prevalência , Antibacterianos/uso terapêutico
2.
Int J Mol Sci ; 24(6)2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36982873

RESUMO

Tumor-associated carbonic anhydrases IX (CAIX) and XII (CAXII) have long been in the spotlight as potential new targets for anti-cancer therapy. Recently, CAIX/CAXII specific inhibitor SLC-0111 has passed clinical phase I study and showed differential response among patients with colorectal cancer (CRC). CRC can be classified into four different consensus molecular subgroups (CMS) showing unique expression patterns and molecular traits. We questioned whether there is a CMS-related CAIX/CAXII expression pattern in CRC predicting response. As such, we analyzed transcriptomic data of tumor samples for CA9/CA12 expression using Cancertool. Protein expression pattern was examined in preclinical models comprising cell lines, spheroids and xenograft tumors representing the CMS groups. Impact of CAIX/CAXII knockdown and SLC-0111 treatment was investigated in 2D and 3D cell culture. The transcriptomic data revealed a characteristic CMS-related CA9/CA12 expression pattern with pronounced co-expression of both CAs as a typical feature of CMS3 tumors. Protein expression in spheroid- and xenograft tumor tissue clearly differed, ranging from close to none (CMS1) to strong CAIX/CAXII co-expression in CMS3 models (HT29, LS174T). Accordingly, response to SLC-0111 analyzed in the spheroid model ranged from no (CMS1) to clear (CMS3), with moderate in CMS2 and mixed in CMS4. Furthermore, SLC-0111 positively affected impact of single and combined chemotherapeutic treatment of CMS3 spheroids. In addition, combined CAIX/CAXII knockdown and more effective treatment with SLC-0111 reduced clonogenic survival of CMS3 modelling single cells. In conclusion, the preclinical data support the clinical approach of targeted CAIX/CAXII inhibition by showing linkage of expression with response and suggest that patients with CMS3-classified tumors would most benefit from such treatment.


Assuntos
Anidrases Carbônicas , Neoplasias Colorretais , Humanos , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Anidrase Carbônica IX/genética , Anidrase Carbônica IX/metabolismo , Anidrases Carbônicas/genética , Anidrases Carbônicas/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Compostos de Fenilureia , Sulfonamidas , Animais
3.
Blood ; 135(23): 2059-2070, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32097467

RESUMO

Noncoding RNAs, including small nucleolar RNAs (snoRNAs), play important roles in leukemogenesis, but the relevant mechanisms remain incompletely understood. We performed snoRNA-focused CRISPR-Cas9 knockout library screenings that targeted the entire snoRNAnome and corresponding host genes. The C/D box containing SNORD42A was identified as an essential modulator for acute myeloid leukemia (AML) cell survival and proliferation in multiple human leukemia cell lines. In line, SNORD42A was consistently expressed at higher levels in primary AML patient samples than in CD34+ progenitors, monocytes, and granulocytes. Functionally, knockout of SNORD42A reduced colony formation capability and inhibited proliferation. The SNORD42A acts as a C/D box snoRNA and directs 2'-O-methylation at uridine 116 of 18S ribosomal RNA (rRNA). Deletion of SNORD42A decreased 18S-U116 2'-O-methylation, which was associated with a specific decrease in the translation of ribosomal proteins. In line, the cell size of SNORD42A deletion carrying leukemia cells was decreased. Taken together, these findings establish that high-level expression of SNORD42A with concomitant U116 18S rRNA 2'-O-methylation is essential for leukemia cell growth and survival.


Assuntos
Proliferação de Células , Metilação de DNA , Leucemia Mieloide Aguda/patologia , RNA Ribossômico 18S/genética , RNA Nucleolar Pequeno/metabolismo , Proteínas Ribossômicas/metabolismo , Sistemas CRISPR-Cas , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , RNA Ribossômico 18S/química , RNA Nucleolar Pequeno/genética , Proteínas Ribossômicas/antagonistas & inibidores , Proteínas Ribossômicas/genética , Células Tumorais Cultivadas
4.
Ann Hematol ; 101(3): 681-691, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34932150

RESUMO

Outcome of allogeneic stem cell transplantation (alloSCT) is hampered by substantial non-relapse mortality (NRM). Given its impact on organ function and immune response, the nutritional status has been suggested as relevant for NRM. We aimed to evaluate the association of NRM with nutritional status prior to alloSCT and in the post-SCT course. In a retrospective single-center study, we analyzed 128 alloSCTs. Besides standard characteristics, nutrition-associated parameters BMI, serum total protein, and serum albumin were recorded before conditioning and at various time points after alloSCT. Association with NRM was evaluated by univariate and multivariate survival analysis. The cohort comprised patients with a median BMI of 26 kg/m2 (16.7-46.9 kg/m2), median serum total protein of 59 g/l (41-77 g/l), and serum albumin of 36 g/l (22-46 g/l) before SCT. NRM at d+100 was 14.8% and at 1 year 26.6%. Prior to SCT, only serum albumin deficiency was associated with increased NRM (p = .010) in multivariate analysis. After SCT (d+30 and d+100), all nutrition-associated parameters decreased (p < .002), but no association of deteriorating nutritional status with NRM was found. In multivariate analysis, serum albumin (p = .03) and severe albumin deficiency (p = .02) correlated with NRM at d+30 and d+100, while BMI and serum total protein did not. In our study, albumin deficiency, particularly prior to alloSCT, shows a strong correlation with NRM. This finding may add to monitoring, risk evaluation, and counseling of patients and serve as a rational for interventions to improve the nutritional status in patients undergoing SCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Estado Nutricional , Adulto , Idoso , Índice de Massa Corporal , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Albumina Sérica/análise , Transplante Homólogo/mortalidade , Resultado do Tratamento , Adulto Jovem
5.
Ann Hematol ; 100(4): 959-968, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33191481

RESUMO

Treatment of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a great challenge. Aiming to evaluate the combination of venetoclax and hypomethylating agents (HMAClax) for the treatment of relapse of myeloid malignancies after alloHSCT, we retrospectively collected data from 32 patients treated at 11 German centers. Venetoclax was applied with azacitidine (n = 13) or decitabine (n = 19); 11 patients received DLI in addition. HMAClax was the first salvage therapy in 8 patients. The median number of cycles per patient was 2 (1-19). All but 1 patient had grade 3/4 neutropenia. Hospital admission for grade 3/4 infections was necessary in 23 patients (72%); 5 of these were fatal. In 30 evaluable patients, overall response rate (ORR) was 47% (14/30, 3 CR MRDneg, 5 CR, 2 CRi, 1 MLFS, 3 PR). ORR was 86% in first salvage patients versus 35% in later salvage patients (p = 0.03). In 6 patients with molecular relapse (MR), ORR was 67% versus 42% in patients with hematological relapse (HR) (n = 24, p = n.s.). After a median follow-up of 8.4 months, 25 patients (78%) had died and 7 were alive. Estimated median overall survival was 3.7 months. Median survival of patients with HMAClax for first versus later salvage therapy was 5.7 and 3.4 months (p = n.s.) and for patients with MR (not reached) compared to HR (3.4 months, p = 0.024). This retrospective case series shows that venetoclax is utilized in various different combinations, schedules, and doses. Toxicity is substantial and patients who receive venetoclax/HMA combinations for MR or as first salvage therapy derive the greatest benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Terapia de Salvação , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Azacitidina/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Terapia Combinada , Metilação de DNA/efeitos dos fármacos , Decitabina/administração & dosagem , Decitabina/efeitos adversos , Decitabina/farmacologia , Avaliação de Medicamentos , Neutropenia Febril/sangue , Neutropenia Febril/induzido quimicamente , Alemanha/epidemiologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/terapia , Contagem de Leucócitos , Síndromes Mielodisplásicas/terapia , Recidiva , Estudos Retrospectivos , Terapia de Salvação/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Condicionamento Pré-Transplante , Síndrome de Lise Tumoral/etiologia
6.
Acta Haematol ; 144(2): 202-211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32906131

RESUMO

INTRODUCTION: Skin rash is a first symptom of acute graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (ASCT) but can also be caused by viruses. The relevance of virus DNA analyses in skin rash for diagnosis and clinical outcome is unknown. OBJECTIVES: To record the frequencies of detection of herpes and parvovirus B19 (ParvoB19) DNA in skin rash within 100 days after ASCT and to analyze their relevance for diagnosis, clinical course, and non-relapse mortality (NRM). METHODS: We retrospectively identified 55 patients with virus DNA analysis for CMV, EBV, HHV6, HHV8, HSV, VZV, or ParvoB19. We assessed the rate of virus DNA detection and studied associations with histological diagnosis, virus DNA from concomitantly analyzed blood, clinical presentation, exanthema treatment, and NRM. RESULTS: CMV, EBV, HHV6, HHV8, HSV, VZV and ParvoB19 DNA were detected in 12.5, 11.8, 10, 0, 0, 2.9, and 26.7% of exanthemas. Histopathological diagnosis was not associated with virus polymerase chain reaction (PCR) results. Detection of CMV, EBV, or HHV6 DNA but not ParvoB19 in skin and blood was associated with PCR results (p = 0.016; p < 0.001; p = 0.067; p = n.a.). Detection of CMV, EBV, HHV6, or ParvoB19 DNA in the skin was not significantly associated with patient, ASCT, or GvHD characteristics. Detection of ParvoB19 but not herpes virus DNA was associated with less immunosuppressive treatment (p = 0.015) and lower NRM (p = 0.041). In multivariate analyses, detection of ParvoB19 was associated with a lower NRM. CONCLUSIONS: Detection of ParvoB19 DNA in exanthema after ASCT might be associated with lower NRM.


Assuntos
Exantema/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Parvovirus B19 Humano/isolamento & purificação , Transplante Homólogo/efeitos adversos , Adulto , Idoso , DNA Viral/análise , DNA Viral/sangue , DNA Viral/metabolismo , Exantema/virologia , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/terapia , Herpesviridae/genética , Herpesviridae/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Parvovirus B19 Humano/genética , Estudos Retrospectivos , Índice de Gravidade de Doença , Pele/patologia , Pele/virologia , Taxa de Sobrevida , Resultado do Tratamento
7.
Z Gastroenterol ; 59(12): 1278-1287, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34687033

RESUMO

BACKGROUND: Practices and hospitals are facing great challenges in coping with the COVID-19-pandemic. So far, data on the impact of the pandemic on gastroenterological facilities are lacking, especially on a temporal course. A database is lacking, especially for the outpatient care sector. University Hospital of Augsburg was commissioned to generate data on this as a part of the collaborative project B-FAST of the Network of University Medicine (NUM). METHODS: Gastroenterological institutions nationwide were surveyed by an online questionnaire. Recruitment was carried out via the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the Professional Association of Gastroenterologists in Private Practice (bng). This manuscript provides an overview of data on the use of protective equipment, pre-interventional testing of patients, staff screening and economic impact over the course of the pandemic. RESULTS: 429 facilities answered the questionnaire. Practices tested their patients pre-interventionally significantly less often than clinics (7.8% vs. 82.6%). In clinics, inpatients (93.1%) were tested significantly more often than outpatients (72.2%). The use of personal protective equipment (PPE) increased significantly during the pandemic. It was shown that over 70% of facilities screened their staff for SARS-CoV-2 without cause. Clinics cancelled elective procedures significantly more often than practices in quarter 4/2020. Procedures and turnover decreased in 2020 compared to the previous year. However, fewer facilities were affected by a loss of revenue than expected in previous studies. CONCLUSION: Our data demonstrate the variable implementation of pre-interventional SARS-CoV-2 testing in outpatient and inpatient care. The use of adequate PPE and staff screening increased during the pandemic.


Assuntos
COVID-19 , Teste para COVID-19 , Endoscopia Gastrointestinal , Alemanha/epidemiologia , Humanos , SARS-CoV-2
8.
Biol Blood Marrow Transplant ; 25(4): e128-e140, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30658222

RESUMO

The curative potential of allogeneic hematopoietic cell transplantation (allo-HCT) in the treatment of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) relies mainly on the graft-versus-leukemia effect. Relapse after allo-HCT occurs in a considerable proportion of patients and has a dismal prognosis, with still very limited curative potential. This review provides an overview of the established and evolving approaches to preventing or treating relapse of AML and MDS after allo-HCT, in the context of novel insight into the biology of relapse. Established prophylactic measures to prevent relapse include optimized conditioning and graft-versus-host disease (GVHD) prophylaxis, as well as donor lymphocyte infusion (DLI) for high-risk patients; novel immunomodulatory interventions and maintenance approaches are still experimental. Improved diagnostics can detect persistent or recurring disease at a molecular level, enabling early preemptive interventions. Established options include hypomethylating agents and DLI. Standard treatments for hematologic relapse include chemotherapy, cessation of immunosuppressive treatment, and DLI. Experimental approaches include molecular targeted therapies, novel immunomodulatory treatments, and second allo-HCT. For all interventions, the potential risks, including occurrence of GVHD, must be weighed against the benefits individually in each patient. Concurrently, prevention and treatment of relapse after allo-HCT remain challenging and unmet medical needs.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Transplante Homólogo/métodos , Feminino , Humanos , Masculino , Recidiva
10.
Nat Mater ; 16(6): 615-621, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28272500

RESUMO

We performed a full mapping of the bulk electronic structure including the Fermi surface and Fermi-velocity distribution vF(kF) of tungsten. The 4D spectral function ρ(EB; k) in the entire bulk Brillouin zone and 6 eV binding-energy (EB) interval was acquired in ∼3 h thanks to a new multidimensional photoemission data-recording technique (combining full-field k-microscopy with time-of-flight parallel energy recording) and the high brilliance of the soft X-rays used. A direct comparison of bulk and surface spectral functions (taken at low photon energies) reveals a time-reversal-invariant surface state in a local bandgap in the (110)-projected bulk band structure. The surface state connects hole and electron pockets that would otherwise be separated by an indirect local bandgap. We confirmed its Dirac-like spin texture by spin-filtered momentum imaging. The measured 4D data array enables extraction of the 3D dispersion of all bands, all energy isosurfaces, electron velocities, hole or electron conductivity, effective mass and inner potential by simple algorithms without approximations. The high-Z bcc metals with large spin-orbit-induced bandgaps are discussed as candidates for topologically non-trivial surface states.

11.
Opt Lett ; 43(19): 4847-4850, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30272755

RESUMO

In the rapid evolution of gastrointestinal endomicroscopy, optical coherence tomography (OCT) has found many diverse applications. Until recently, the micro-opto-electro-mechanical systems (MOEMS) technology has been playing a key role in shaping the miniaturization of these components. We report here, to the best of our knowledge, a novel endoscopic microsystem. It is based on a spectrally tuned MOEMS Mirau micro-interferometer integrated with micro-electro-mechanical systems (MEMS) electro-thermal micro-scanner, operating in the regime of swept-source (SS) OCT imaging. This Letter validates our initial proof-of-concept toward the development of such MOEMS probe and the presentation of experimental performances of the resulting SS-OCT microsystem.

12.
BMC Cancer ; 18(1): 941, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30285657

RESUMO

BACKGROUND: Chronic active Epstein-Barr virus (EBV) infection (CAEBV) of the T-/NK-cell type, systemic form is a rare and potentially life-threatening illness caused by persistent EBV infection. The highest incidence is found in children and adolescents with increased frequency among Asians and Native Americans, while the disease is uncommon in Western countries. Typically patients present with unspecific symptoms, like fever, lymphadenopathy, hepatosplenomegaly and liver dysfunction. Due to fatal complications including hemophagocytic syndrome, coagulopathy, multiple organ failure and development of EBV-positive lymphoproliferative disease (LPD) or lymphoma early diagnosis is critical for successful treatment. However, in consequence of the lack of experience due to the low incidence in Europe, a broad spectrum of clinical manifestations and a particularly unexpected group of patients, diagnosis can be challenging. Inhere we describe the clinicopathological findings of an African adult with CAEBV associated LPD with a brief review of the literature. CASE PRESENTATION: A 42-year-old African man with fever, enlargement of the spleen and a suspected epileptic seizure was referred to our hospital. Diagnostic testing repeatedly revealed a massive EBV-DNA load in peripheral blood. Whole-body PET-CT-scan presented a strong uptake at multiple bone marrow sites, the thyroid and the adrenal glands. Histopathological analysis of bone marrow and thyroid gland revealed a highly proliferating, atypical and predominantly intravascular cytotoxic T-cell population with intracellular EBV-encoded RNA. Clonality analysis revealed the presence of polyclonal T-cell-receptor. Based on these findings a CAEBV of the T-/NK-cell type, systemic form was diagnosed. Subsequent therapy including three cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisolone resulted in decreased EBV load, clinical improvement and ongoing complete remission. CONCLUSION: Adult-onset CAEBV of T/NK-cell type usually comprises a poor prognosis and is extremely rare in Western countries. Therefore, our case highlights the need for a clinical awareness of this disease in patients with systemic illness and for a comprehensive multidisciplinary diagnostic approach to facilitate diagnosis. Treatment options include antiviral drugs, immunosuppressive agents and systemic chemotherapy with or without allogeneic stem cell transplantation. Given the limited data these options need to be decided upon in each patient individually considering severity of the disease, comorbidities and response.


Assuntos
Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/fisiologia , Subpopulações de Linfócitos T/virologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , População Negra , Doença Crônica , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/imunologia , Humanos , Imunofenotipagem , Linfonodos/metabolismo , Linfonodos/patologia , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisona/uso terapêutico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Migrantes , Resultado do Tratamento , Vincristina/uso terapêutico , Carga Viral
13.
Mol Psychiatry ; 22(10): 1395-1412, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28696430

RESUMO

Suicide is a major public health concern and a leading cause of death in most societies. Suicidal behaviour is complex and heterogeneous, likely resulting from several causes. It associates with multiple factors, including psychopathology, personality traits, early-life adversity and stressful life events, among others. Over the past decades, studies in fields ranging from neuroanatomy, genetics and molecular psychiatry have led to a model whereby behavioural dysregulation, including suicidal behaviour (SB), develops as a function of biological adaptations in key brain systems. More recently, the unravelling of the unique epigenetic processes that occur in the brain has opened promising avenues in suicide research. The present review explores the various facets of the current knowledge on suicidality and discusses how the rapidly evolving field of neurobehavioural epigenetics may fuel our ability to understand, and potentially prevent, SB.


Assuntos
Suicídio/psicologia , Encéfalo/fisiopatologia , Epigênese Genética/genética , Epigenômica , Humanos , Acontecimentos que Mudam a Vida , Transtornos Mentais/fisiopatologia , Doenças do Sistema Nervoso , Neuropatologia , Fatores de Risco , Ideação Suicida , Tentativa de Suicídio/prevenção & controle , Tentativa de Suicídio/psicologia
14.
Eur J Haematol ; 101(1): 115-118, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29624748

RESUMO

Recurrence of primary central nervous system lymphoma (PCNSL) after high-dose chemotherapy with autologous stem cell transplantation (ASCT) usually has a poor overall prognosis with limited treatment options. Data on repeated ASCT are sparse. Checkpoint inhibitor maintenance therapy has also not been reported in PCNSL. Here, we report the first documented case of a successful third ASCT in second relapse of PCNSL. Whole-exome sequencing identified a hypermutated tumor genotype. Additionally, immunohistochemistry on pretreatment tumor tissue revealed infiltrates of PD-1+ cytolytic T cells. These alterations provided a rationale for subsequent nivolumab maintenance treatment. Therapy led to a long-term, ongoing complete remission. In eligible patients with recurrent MTX-sensitive PCNSL, multiple long-term remissions can be induced by repetition of high-dose MTX-based chemotherapy followed by autologous retransplantation. Subsequent immune checkpoint inhibitor maintenance therapy might be able to prolong or maintain remission.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Transplante de Células-Tronco Hematopoéticas , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/terapia , Adulto , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/imunologia , Feminino , Expressão Gênica , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Nivolumabe , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Indução de Remissão , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Transplante Autólogo , Resultado do Tratamento , Sequenciamento do Exoma
15.
Phys Chem Chem Phys ; 20(22): 15528-15534, 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29808838

RESUMO

Electron paramagnetic resonance (EPR) is a powerful technique to investigate the electronic and magnetic properties of a wide range of materials. We present the first combined terahertz (THz) field and frequency domain electron paramagnetic resonance (HFEPR/FDMR) spectrometer designed to investigate the electronic structure and magnetic properties of molecular systems, thin films and solid state materials in a very broad frequency range of 85-1100 GHz. In this paper, we show high resolution frequency-field (Zeeman) maps (170-380 GHz by 0-15 T) recorded on two single-molecule magnets, [Mn2(saltmen)2(ReO4)2] and [Mn2(salpn)2(H2O)2](ClO4)2, which give direct access to the field-dependence of the energy level diagram. Furthermore, supression of standing waves in the described system and the sensitivity in field and frequency domain operations is evaluated and discussed.

16.
Pacing Clin Electrophysiol ; 41(1): 22-27, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29211301

RESUMO

BACKGROUND: Pulmonary vein isolation (PVI) has become a widely accepted therapy in patients suffering from symptomatic atrial fibrillation (AF). HYPOTHESIS: AF-free survival differs in patients with left common pulmonary vein (LCPV) after PVI with second-generation cryoballoon. METHODS: We included patients scheduled for first PVI for paroxysmal or persistent AF. Symptomatic and/or documented arrhythmia episodes (>30 seconds) were defined as AF recurrence, excluding a 3-month blanking period. RESULTS: We observed a LCPV in 37 of 270 consecutive patients (13.7%). Analyses were performed in a 1:1 propensity score matched cohort of 68 patients. During a median follow-up of 77.0 weeks, 37 patients (54.4%) had recurrent AF. The prevalence of LCPV was numerically higher in patients with AF recurrence (62.2% vs 35.5%, P  =  0.051) and Kaplan-Meier analysis showed lower AF-free survival in patients with existence of a LCPV (P  =  0.028). At 1-year follow-up, 70.6% of patients without versus 55.1% of patients with LCPV were free of AF. Multivariate Cox regression analysis revealed presence of a LCPV (hazard ratio [HR]: 2.996), chronic heart failure (HR: 3.423), and mitral regurgitation > I° (HR: 2.571) as predictors of AF recurrence. CONCLUSION: Patients with LCPV had significantly reduced AF-free survival after ablation with the second-generation cryoballoon, despite similar acutely successful PVIs.


Assuntos
Fibrilação Atrial/cirurgia , Criocirurgia/instrumentação , Veias Pulmonares/cirurgia , Idoso , Fibrilação Atrial/diagnóstico por imagem , Angiografia Coronária , Ecocardiografia , Feminino , Fluoroscopia , Alemanha , Humanos , Masculino , Pontuação de Propensão , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
17.
Adv Exp Med Biol ; 1093: 1-20, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30306468

RESUMO

Introduced more than two decades ago, computer-aided orthopaedic surgery (CAOS) has emerged as a new and independent area, due to the importance of treatment of musculoskeletal diseases in orthopaedics and traumatology, increasing availability of different imaging modalities and advances in analytics and navigation tools. The aim of this chapter is to present the basic elements of CAOS devices and to review state-of-the-art examples of different imaging modalities used to create the virtual representations, of different position tracking devices for navigation systems, of different surgical robots, of different methods for registration and referencing, and of CAOS modules that have been realized for different surgical procedures. Future perspectives will be outlined. It is expected that the recent advancement on smart instrumentation, medical robotics, artificial intelligence, machine learning, and deep learning techniques, in combination with big data analytics, may lead to smart CAOS systems and intelligent orthopaedics in the near future.


Assuntos
Procedimentos Ortopédicos , Ortopedia/tendências , Robótica , Cirurgia Assistida por Computador , Inteligência Artificial , Previsões , Humanos , Doenças Musculoesqueléticas/cirurgia
18.
Adv Exp Med Biol ; 1093: 93-103, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30306475

RESUMO

This chapter introduces a solution called "3X-knee" that can robustly derive 3D models of the lower extremity from 2D long leg standing X-ray radiographs for preoperative planning and postoperative treatment evaluation of total knee arthroplasty (TKA). There are three core components in 3X-knee technology: (1) a knee joint immobilization apparatus, (2) an X-ray image calibration phantom, and (3) a statistical shape model-based 2D-3D reconstruction algorithm. These three components are integrated in a systematic way in 3X-knee to derive 3D models of the complete lower extremity from 2D long leg standing X-ray radiographs acquired in weight-bearing position. More specifically, the knee joint immobilization apparatus will be used to rigidly fix the X-ray calibration phantom with respect to the underlying anatomy during the image acquisition. The calibration phantom then serves two purposes. For one side, the phantom will allow one to calibrate the projection parameters of any acquired X-ray image. For the other side, the phantom also allowsone to track positions of multiple X-ray images of the underlying anatomy without using any additional positional tracker, which is a prerequisite condition for the third component to compute patient-specific 3D models from 2D X-ray images and the associated statistical shape models. Validation studies conducted on both simulated X-ray images and on patients' X-ray data demonstrate the efficacy of the present solution.


Assuntos
Artroplastia do Joelho , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Articulação do Joelho/diagnóstico por imagem , Algoritmos , Humanos , Tomografia Computadorizada por Raios X , Raios X
19.
Adv Exp Med Biol ; 1093: 157-168, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30306480

RESUMO

Modern computerized planning tools for periacetabular osteotomy (PAO) use either morphology-based or biomechanics-based methods. The latter rely on estimation of peak contact pressures and contact areas using either patient-specific or constant thickness cartilage models. We performed a finite element analysis investigating the optimal reorientation of the acetabulum in PAO surgery based on simulated joint contact pressures and contact areas using patient-specific cartilage model. Furthermore we investigated the influences of using patient-specific cartilage model or constant thickness cartilage model on the biomechanical simulation results. Ten specimens with hip dysplasia were used in this study. Image data were available from CT arthrography studies. Bone models were reconstructed. Mesh models for the patient-specific cartilage were defined and subsequently loaded under previously reported boundary and loading conditions. Peak contact pressures and contact areas were estimated in the original position. Afterward we used validated preoperative planning software to change the acetabular inclination by an increment of 5° and measured the lateral center-edge angle (LCE) at each reorientation position. The position with the largest contact area and the lowest peak contact pressure was defined as the optimal position. In order to investigate the influence of using patient-specific cartilage model or constant thickness cartilage model on the biomechanical simulation results, the same procedure was repeated with the same bone models but with a cartilage mesh of constant thickness. Comparison of the peak contact pressures and the contact areas between these two different cartilage models showed that good correlation between these two cartilage models for peak contact pressures (r = 0.634 ∈[0.6, 0.8], p < 0.001) and contact areas (r = 0.872 > 0.8, p < 0.001). For both cartilage models, the largest contact areas and the lowest peak pressures were found at the same position. Our study is the first study comparing peak contact pressures and contact areas between patient-specific and constant thickness cartilage models during PAO planning. Good correlation for these two models was detected. Computer-assisted planning with FE modeling using constant thickness cartilage models might be a promising PAO planning tool when a conventional CT is available.


Assuntos
Acetábulo/cirurgia , Cartilagem Articular , Modelos Anatômicos , Osteotomia , Cirurgia Assistida por Computador , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos
20.
Adv Exp Med Biol ; 1093: 143-155, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30306479

RESUMO

Periacetabular osteotomy (PAO) is an effective approach for surgical treatment of hip dysplasia in young adults. However, achieving an optimal acetabular reorientation during PAO is the most critical and challenging step. Routinely, the correct positioning of the acetabular fragment largely depends on the surgeon's experience and is done under fluoroscopy to provide the surgeon with continuous live x-ray guidance. Our developed system starts with a fully automatic detection of the acetabular rim, which allows for quantifying the acetabular 3D morphology with parameters such as acetabular orientation, femoral head extrusion index (EI), lateral center-edge (LCE) angle, and total and regional femoral head coverage (FHC) ratio for computer-assisted diagnosis, planning, and simulation of PAO. Intraoperative navigation is conducted to implement the preoperative plan. Two validation studies were conducted on four sawbone models to evaluate the efficacy of the system intraoperatively and postoperatively. By comparing the preoperatively planned situation with the intraoperatively achieved situation, average errors of 0.6° ± 0.3°, 0.3° ± 0.2°, and 1.1° ± 1.1° were found, respectively, along three motion directions (flexion/extension, abduction/adduction, and external rotation/internal rotation). In addition, by comparing the preoperatively planned situation with the postoperative results, average errors of 0.9° ± 0.3° and 0.9° ± 0.7° were found for inclination and anteversion, respectively.


Assuntos
Diagnóstico por Computador , Luxação Congênita de Quadril/cirurgia , Osteotomia , Cirurgia Assistida por Computador , Acetábulo , Humanos , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
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