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A first-principles description of the primary photochemical processes that drive photosynthesis and sustain life on our planet remains one of the grand challenges of modern science. Recent research established that explicit incorporation of protein electrostatics in excited-state calculations of photosynthetic pigments, achieved for example with quantum-mechanics/molecular-mechanics (QM/MM) approaches, is essential for a meaningful description of the properties and function of pigment-protein complexes. Although time-dependent density functional theory has been used productively so far in QM/MM approaches for the study of such systems, this methodology has limitations. Here we pursue for the first time a QM/MM description of the reaction center in the principal enzyme of oxygenic photosynthesis, Photosystem II, using multireference wave function theory for the high-level QM region. We identify best practices and establish guidelines regarding the rational choice of active space and appropriate state-averaging for the efficient and reliable use of complete active space self-consistent field (CASSCF) and the N-electron valence state perturbation theory (NEVPT2) in the prediction of low-lying excited states of chlorophyll and pheophytin pigments. Given that the Gouterman orbitals are inadequate as a minimal active space, we define specific minimal and extended active spaces for the NEVPT2 description of electronic states that fall within the Q and B bands. Subsequently, we apply our multireference-QM/MM protocol to the description of all pigments in the reaction center of Photosystem II. The calculations reproduce the electrochromic shifts induced by the protein matrix and the ordering of site energies consistent with the identity of the primary donor (ChlD1) and the experimentally known asymmetric and directional electron transfer. The optimized protocol sets the stage for future multireference treatments of multiple pigments, and hence for multireference studies of charge separation, while it is transferable to the study of any photoactive embedded tetrapyrrole system.
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The identity and insertion pathway of the substrate oxygen atoms that are coupled to dioxygen by the oxygen-evolving complex (OEC) remains a central question toward understanding Nature's water oxidation mechanism. In several studies, ammonia has been used as a small "water analogue" to elucidate the pathway of substrate access to the OEC and to aid in determining which of the oxygen ligands of the tetramanganese cluster are substrates for O-O bond formation. On the basis of structural and spectroscopic investigations, five first-sphere binding modes of ammonia have been suggested, involving either substitution of an existing H2O/OH-/O2- group or addition as an extra ligand to a metal ion of the Mn4CaO5 cluster. Some of these modes, specifically the ones involving substitution, have already been subject to spectroscopy-oriented quantum chemical investigations, whereas more recent suggestions that postulate the addition of ammonia have not been examined so far with quantum chemistry for their agreement with spectroscopic data. Herein, we use a common structural framework and theoretical methodology to evaluate structural models of the OEC that represent all proposed modes of first-sphere ammonia interaction with the OEC in its S2 state. Criteria include energetic, magnetic, kinetic, and spectroscopic properties compared against available experimental EPR, ENDOR, ESEEM, and EDNMR data. Our results show that models featuring ammonia replacing one of the two terminal water ligands on Mn4 align best with experimental data, while they definitively exclude substitution of a bridging µ-oxo ligand as well as incorporation of ammonia as a sixth ligand on Mn1 or Mn4.
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Photosystem II, the water splitting enzyme of photosynthesis, utilizes the energy of sunlight to drive the four-electron oxidation of water to dioxygen at the oxygen-evolving complex (OEC). The OEC harbors a Mn4CaO5 cluster that cycles through five oxidation states Si (i = 0-4). The S3 state is the last metastable state before the O2 evolution. Its electronic structure and nature of the S2 â S3 transition are key topics of persisting controversy. Most spectroscopic studies suggest that the S3 state consists of four Mn(IV) ions, compared to the Mn(III)Mn(IV)3 of the S2 state. However, recent crystallographic data have received conflicting interpretations, suggesting either metal- or ligand-based oxidation, the latter leading to an oxyl radical or a peroxo moiety in the S3 state. Herein, we utilize high-energy resolution fluorescence detected (HERFD) X-ray absorption spectroscopy to obtain a highly resolved description of the Mn K pre-edge region for all S-states, paying special attention to use chemically unperturbed S3 state samples. In combination with quantum chemical calculations, we achieve assignment of specific spectroscopic features to geometric and electronic structures for all S-states. These data are used to confidently discriminate between the various suggestions concerning the electronic structure and the nature of oxidation events in all observable catalytic intermediates of the OEC. Our results do not support the presence of either peroxo or oxyl in the active configuration of the S3 state. This establishes Mn-centered storage of oxidative equivalents in all observable catalytic transitions and constrains the onset of the O-O bond formation until after the final light-driven oxidation event.
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DNA G-quadruplexes (GQs) are of great interest due to their involvement in crucial biological processes such as telomerase maintenance and gene expression. Furthermore, they are reported as catalytically active DNAzymes and building blocks in bio-nanotechnology. GQs exhibit remarkable structural diversity and conformational heterogeneity, necessitating precise and reliable tools to unravel their structure-function relationships. Here, we present insights into the structure and conformational flexibility of a unimolecular GQ with high spatial resolution via electron-nuclear double resonance (ENDOR) experiments combined with Cu(II) and fluorine labeling. These findings showcase the successful application of the 19 F-ENDOR methodology at 34â GHz, overcoming the limitations posed by the complexity and scarcity of higher-frequency spectrometers. Importantly, our approach retains both sensitivity and orientational resolution. This integrated study not only enhances our understanding of GQs but also expands the methodological toolbox for studying other macromolecules.
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Cobre , Quadruplex G , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Cobre/químicaRESUMO
Recent advances in serial femtosecond crystallography (SFX) of photosystem II (PSII), enabled by X-ray free electron lasers (XFEL), provided the first geometric models of distinct intermediates in the catalytic S-state cycle of the oxygen-evolving complex (OEC). These models are obtained by flash-advancing the OEC from the dark-stable state (S1) to more oxidized intermediates (S2 and S3), eventually cycling back to the most reduced S0. However, the interpretation of these models is controversial because geometric parameters within the Mn4CaO5 cluster of the OEC do not exactly match those expected from coordination chemistry for the spectroscopically verified manganese oxidation states of the distinct S-state intermediates. Here we focus on the first catalytic transition, S1 â S2, which represents a one-electron oxidation of the OEC. Combining geometric and electronic structure criteria, including a novel effective oxidation state approach, we analyze existing 1-flash (1F) SFX-XFEL crystallographic models that should depict the S2 state of the OEC. We show that the 1F/S2 equivalence is not obvious, because the Mn oxidation states and total unpaired electron counts encoded in these models are not fully consistent with those of a pure S2 state and with the nature of the S1 â S2 transition. Furthermore, the oxidation state definition in two-flashed (2F) structural models is practically impossible to elucidate. Our results advise caution in the extraction of electronic structure information solely from the literal interpretation of crystallographic models and call for re-evaluation of structural and mechanistic interpretations that presume exact correspondence of such models to specific catalytic intermediates of the OEC.
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BACKGROUND: Outcomes of robotic-assisted coronary artery bypass grafting in pregnant women have not been assessed. OBJECTIVE: This study aimed to understand the importance of minimally invasive robotic-assisted coronary artery bypass grafting in pregnant woman with coronary artery disease. We describe the case of a G3P1011 woman at 19+6 weeks' gestation presenting with a non-ST myocardial infarction treated with off-pump hybrid robotic-assisted revascularization. STUDY DESIGN: This study describes the surgical approach for a pregnant woman presenting with non-ST myocardial infarction treated with hybrid robotic-assisted revascularization. RESULTS: A coronary angiography demonstrated a culprit lesion of 90% stenosis in the left anterior descending coronary artery and an 80% stenosis in the right coronary artery. Because of the high rate of complications with traditional coronary artery bypass grafting, the heart team opted for hybrid robotic-assisted revascularization and the postoperative recovery was uneventful. CONCLUSION: Robotic coronary artery bypass grafting can be the preferred surgical choice to decrease maternal and fetal mortality in patients undergoing coronary artery bypass grafting, and it is an important tool in the surgical armamentarium.
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Oxalate decarboxylase from Bacillus subtilis is a binuclear Mn-dependent acid stress response enzyme that converts the mono-anion of oxalic acid into formate and carbon dioxide in a redox neutral unimolecular disproportionation reaction. A π-stacked tryptophan dimer, W96 and W274, at the interface between two monomer subunits facilitates long-range electron transfer between the two Mn ions and plays an important role in the catalytic mechanism. Substitution of W96 with the unnatural amino acid 5-hydroxytryptophan leads to a persistent EPR signal which can be traced back to the neutral radical of 5-hydroxytryptophan with its hydroxyl proton removed. 5-Hydroxytryptophan acts as a hole sink preventing the formation of Mn(III) at the N-terminal active site and strongly suppresses enzymatic activity. The lower boundary of the standard reduction potential for the active site Mn(II)/Mn(III) couple can therefore be estimated as 740 mV against the normal hydrogen electrode at pH 4, the pH of maximum catalytic efficiency. Our results support the catalytic importance of long-range electron transfer in oxalate decarboxylase while at the same time highlighting the utility of unnatural amino acid incorporation and specifically the use of 5-hydroxytryptophan as an energetic sink for hole hopping to probe electron transfer in redox proteins.
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5-Hidroxitriptofano , Elétrons , 5-Hidroxitriptofano/metabolismo , Manganês/química , Oxirredução , Ácido Oxálico , Espectroscopia de Ressonância de Spin EletrônicaRESUMO
INTRODUCTION: Femoral-femoral Veno-Venous ExtraCorporeal Life Support (V-V ECLS) has been associated with higher infections rates, vascular site bleeding complications, and restricted patient mobility. Jugular or bicaval dual lumen V-V ECLS conceptually overcomes some of these adverse factors, but experience has shown that jugular vein cannulation still limits mobility and has increased bleeding complications. Technique and outcomes of subclavian vein single-cannulation with Crescent jugular dual-lumen V-V ECLS is described. METHOD: five patients with COVID-19 related acute respiratory distress syndrome (ARDS) underwent right subclavian vein V-V ECLS placement with the Crescent 32 French jugular dual-lumen V-V ECLS catheter. A standardized percutaneous technique was developed that allowed efficient insertion without need for any specialized imaging (i.e. transesophageal echocardiogram) and outcomes assessed. RESULTS: Mean age of the five patients was 41.2 years, all obese with an average basal mass index of 45.2 kg/m2 and mean days to decannulation of 24.2 days. Outcomes discovered included; improved patient mobility allowing physical rehabilitation, no vascular access site related complications requiring surgery or endovascular intervention, and none had evidence of superior vena cava syndrome. One patient had subclavian/axillary vein thrombosis with resolution after 3 months of direct-acting oral anticoagulants, and one patient had blood cultures positive at day 37, nearing decannulation. CONCLUSION: Subclavian vein access for crescent jugular dual lumen V-V ECLS catheter appears to be safe and feasible with added benefits of decreased bleeding and increased mobility over jugular or femoral-femoral access site for long term V-V ECLS support in COVID-19 related ARDS patients.
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Spin-state energetics of transition metal complexes remain one of the most challenging targets for electronic structure methods. Among single-reference wave function approaches, local correlation approximations to coupled cluster theory, most notably the domain-based local pair natural orbital (DLPNO) approach, hold the promise of bringing the accuracy of coupled cluster theory with single, double, and perturbative triple excitations, CCSD(T), to molecular systems of realistic size with acceptable computational cost. However, recent studies on spin-state energetics of iron-containing systems raised doubts about the ability of the DLPNO approach to adequately and systematically approximate energetics obtained by the reference-quality complete active space second-order perturbation theory with coupled-cluster semicore correlation, CASPT2/CC. Here, we revisit this problem using a diverse set of iron complexes and examine several aspects of the application of the DLPNO approach. We show that DLPNO-CCSD(T) can accurately reproduce both CASPT2/CC and canonical CCSD(T) results if two basic principles are followed. These include the consistent use of the improved iterative (T1) versus the semicanonical perturbative triple corrections and, most importantly, a simple two-point extrapolation to the PNO space limit. The latter practically eliminates errors arising from the default truncation of electron-pair correlation spaces and should be viewed as standard practice in applications of the method to transition metal spin-state energetics. Our results show that reference-quality results can be readily achieved with DLPNO-CCSD(T) if these principles are followed. This is important also in view of the applicability of the method to larger single-reference systems and multinuclear clusters, whose treatment of dynamic correlation would be challenging for multireference-based approaches.
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Understanding the structure and function of lytic polysaccharide monooxygenases (LPMOs), copper enzymes that degrade recalcitrant polysaccharides, requires the reliable atomistic interpretation of electron paramagnetic resonance (EPR) data on the Cu(II) active site. Among various LPMO families, the chitin-active PlAA10 shows an intriguing phenomenology with distinct EPR signals, a major rhombic and a minor axial signal. Here, we combine experimental and computational investigations to uncover the structural identity of these signals. X-band EPR spectra recorded at different pH values demonstrate pH-dependent population inversion: the major rhombic signal at pH 6.5 becomes minor at pH 8.5, where the axial signal dominates. This suggests that a protonation change is involved in the interconversion. Precise structural interpretations are pursued with quantum chemical calculations. Given that accurate calculations of Cu g-tensors remain challenging for quantum chemistry, we first address this problem via a thorough calibration study. This enables us to define a density functional that achieves accurate and reliable prediction of g-tensors, giving confidence in our evaluation of PlAA10 LPMO models. Large models were considered that include all parts of the protein matrix surrounding the Cu site, along with the characteristic second-sphere features of PlAA10. The results uniquely identify the rhombic signal with a five-coordinate Cu ion bearing two water molecules in addition to three N-donor ligands. The axial signal is attributed to a four-coordinate Cu ion where only one of the waters remains bound, as hydroxy. Alternatives that involve decoordination of the histidine brace amino group are unlikely based on energetics and spectroscopy. These results provide a reliable spectroscopy-consistent view on the plasticity of the resting state in PlAA10 LPMO as a foundation for further elucidating structure-property relationships and the formation of catalytically competent species. Our strategy is generally applicable to the study of EPR parameters of mononuclear copper-containing metalloenzymes.
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Oxigenases de Função Mista , Photorhabdus , Cobre/química , Espectroscopia de Ressonância de Spin Eletrônica , Oxigenases de Função Mista/química , Photorhabdus/enzimologia , Polissacarídeos/químicaRESUMO
The electronic and geometric structures of the water-oxidizing complex of photosystem II in the steps of the catalytic cycle that precede dioxygen evolution remain hotly debated. Recent structural and spectroscopic investigations support contradictory redox formulations for the active-site Mn4 CaOx cofactor in the final metastable S3 state. These range from the widely accepted MnIV 4 oxo-hydroxo model, which presumes that O-O bond formation occurs in the ultimate transient intermediate (S4 ) of the catalytic cycle, to a MnIII 2 MnIV 2 peroxo model representative of the contrasting "early-onset" O-O bond formation hypothesis. Density functional theory energetics of suggested S3 redox isomers are inconclusive because of extreme functional dependence. Here, we use the power of the domain-based local pair natural orbital approach to coupled cluster theory, DLPNO-CCSD(T), to present the first correlated wave function theory calculations of relative stabilities for distinct redox-isomeric forms of the S3 state. Our results enabled us to evaluate conflicting models for the S3 state of the oxygen-evolving complex (OEC) and to quantify the accuracy of lower-level theoretical approaches. Our assessment of the relevance of distinct redox-isomeric forms for the mechanism of biological water oxidation strongly disfavors the scenario of early-onset O-O formation advanced by literal interpretations of certain crystallographic models. This work serves as a case study in the application of modern coupled cluster implementations to redox isomerism problems in oligonuclear transition metal systems.
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Manganês , Complexo de Proteína do Fotossistema II , Isomerismo , Oxirredução , Oxigênio , Complexo de Proteína do Fotossistema II/metabolismo , ÁguaRESUMO
Saphenous vein graft aneurysm is an uncommon condition and knowledge about its natural history, and a multi-specialty heart team approach is of utmost importance for better clinical outcomes. This case highlights importance of percutaneous intervention as a viable therapeutic option in the case of saphenous vein graft aneurysms.
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The tetramanganese-calcium cluster of the oxygen-evolving complex of photosystem II adopts electronically and magnetically distinct but interconvertible valence isomeric forms in its first light-driven oxidized catalytic state, S2 . This bistability is implicated in gating the final catalytic states preceding O-O bond formation, but it is unknown how the biological system enables its emergence and controls its effect. Here we show that the Mn4 CaO5 cluster in the resting (dark-stable) S1 state adopts orientational Jahn-Teller isomeric forms arising from a directional change in electronic configuration of the "dangler" MnIII ion. The isomers are consistent with available structural data and explain previously unresolved electron paramagnetic resonance spectroscopic observations on the S1 state. This unique isomerism in the resting state is shown to be the electronic origin of valence isomerism in the S2 state, establishing a functional role of orientational Jahn-Teller isomerism unprecedented in biological or artificial catalysis.
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Cálcio/química , Complexos de Coordenação/química , Manganês/química , Água/química , Catálise , Espectroscopia de Ressonância de Spin Eletrônica , Isomerismo , Oxigênio/química , Complexo de Proteína do Fotossistema II/química , Complexo de Proteína do Fotossistema II/metabolismoRESUMO
Three sets of criteria (International Society of Amyloidosis [ISA], Palladini and Kastritis) were independently developed for staging, progression and response criteria to predict renal survival in patients with AL amyloidosis. We evaluated these criteria using a cohort of 495 newly diagnosed AL amyloidosis patients with renal involvement using time to event competing risk analysis at baseline, 3, 6 and 12 months after treatment. Only Palladini and Kastritis had a staging system and both predicted a higher risk of end stage renal disease (ESRD) in the stage III vs stage I patients but only the Palladini model was predictive for stage II patients. At 3 months, risk of ESRD was significantly higher for Palladini and ISA renal progression (hazard ratio [HR] 2.8 [95% CI: 1.5-5.3, p = .001] and 2.5 [CI: 1.4-4.6, p = .004, respectively]), but renal response was not significantly protective; conversely, the risk of ESRD was not significantly higher for the Kastritis renal progression, but was significantly protective for the Kastritis renal responders (HR 0.38 [95% CI: 0.17-0.84], p = .017). Both progression and response with ISA, Palladini and Kastritis criteria were predictive of ESRD at 6 months and 12 months. While the Palladini staging criteria at baseline, and the ISA and Palladini criteria for progression at 3 months performed better than the Kastritis criteria at baseline and 3 months post-treatment, the Kastritis criteria performed better for response 3 months after treatment. All three sets of criteria performed well at and after 6 months post-treatment. These differences are important when choosing endpoints for clinical trials.
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Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Falência Renal Crônica/etiologia , Índice de Gravidade de Doença , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Rim/fisiopatologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , PrognósticoRESUMO
BACKGROUND: Fibrillary glomerulonephritis (FGN) is a rare type of glomerulonephritis with poor prognosis, with no known effective therapies available for treatment. The objective of the study was to evaluate the efficacy and safety of rituximab in treatment of patients with FGN and to investigate the effect of rituximab on DNAJB9 levels. METHODS: This was a pilot prospective clinical trial in which patients with idiopathic FGN were treated with two courses of rituximab (1 g each) 2 weeks apart at the beginning and then again at 6 months. Primary outcome was defined as preservation of kidney function at 12 months with stable or increased creatinine clearance. Secondary outcome was defined as achieving complete remission (CR) defined as proteinuria <300 mg/24 h or partial remission (PR) with proteinuria <3 g/24 h and at least 50% reduction in the proteinuria. DNAJB9 levels were also measured in the serum at baseline, 6 and 12 months. RESULTS: The creatinine clearance did not change significantly during this time, from 47.7 mL/min/1.73 m2 at baseline to 43.7 mL/min/1.73 m2 during follow-up (P = 0.15). Proteinuria declined from 4.43 (1.6-5.53) g/24 h at baseline to 1.9 (0.46-5.26) g/24 h at 12 months but did not reach significance (P = 0.06). None of the patients reached CR, and 3 of the 11 achieved PR. There was no change in the DNAJB9 levels following treatment with rituximab. The most common adverse event was nasal congestion, fatigue and muscle cramps. CONCLUSIONS: Treatment of patients with two courses of rituximab over a span of 6 months was associated with stabilization of renal function but did not result in a significant change in proteinuria and with no change in the DNAJB9 levels.
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Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores/análise , Glomerulonefrite/tratamento farmacológico , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Glomerulonefrite/classificação , Glomerulonefrite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, ß2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.
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Injúria Renal Aguda/complicações , Nefropatias/mortalidade , Mieloma Múltiplo/complicações , Transplante de Células-Tronco/mortalidade , Injúria Renal Aguda/patologia , Injúria Renal Aguda/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Feminino , Seguimentos , Humanos , Cadeias Leves de Imunoglobulina/sangue , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Prognóstico , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Taxa de Sobrevida , Transplante AutólogoRESUMO
The amyloidoses are a group of disorders with overlapping clinical presentations, characterized by aggregation and tissue deposition of misfolded proteins. The nature and source of the amyloidogenic protein determines therapy, therefore correct subtyping is critical to patient management. We report the clinicopathologic features of nine patients diagnosed with two amyloid types confirmed by liquid chromatography-coupled tandem mass spectrometry. The most common types were transthyrethin (n = 9) and immunoglobulin-derived (n = 7). Two patients did not have immunoglobulin-derived amyloidosis despite the presence of a monoclonal gammopathy. Eight patients were diagnosed with two types concurrently, and one patient had an 11-year interval between diagnoses. Histopathological distribution of amyloid was variable with vascular, interstitial, and periosteal deposits seen. Identification of a second type was incidental in seven patients, but led to genetic counselling in one patient and therapy directed at both amyloid subtypes in another. With longer survival of myeloma and AL amyloidosis patients and increasing prevalence of patients with wild-type transthyretin amyloidosis due to an aging population, the phenomenon of two amyloid types in a single patient will be encountered more frequently. In light of revolutionary new therapies for transthyretin amyloidosis (patisiran, tafamidis, and inotersen), recognition of dual amyloid types is highly clinically relevant.
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Amiloidose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Cromatografia Líquida , Diagnóstico Diferencial , Feminino , Humanos , Microdissecção e Captura a Laser , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Especificidade de Órgãos , Avaliação de SintomasRESUMO
Multiple Myeloma is a plasma cell proliferative disorder that commonly involves the kidney. Renal impairment is a serious complication during the course of the disease that is associated with increased morbidity and mortality. Light chain cast nephropathy is the predominant pattern of renal injury in Multiple Myeloma. This review article focuses on the pathophysiology and diagnostic approach of myeloma cast nephropathy. The management of precipitating factors as well as anti-plasma cell treatment modalities in the context of renal impairment are also discussed.