A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains.

Positron emission tomography (PET) allows biomolecular tracking but PET monitoring of brain networks has been hampered by a lack of suitable reporters. Here, we take advantage of bacterial dihydrofolate reductase, ecDHFR, and its unique antagonist, TMP, to facilitate in vivo imaging in the brain. Peripheral administration of radiofluorinated and fluorescent TMP analogs enabled PET and intravital microscopy, respectively, of neuronal ecDHFR expression in mice. This technique can be used to the visualize neuronal circuit activity elicited by chemogenetic manipulation in the mouse hippocampus. Notably, ecDHFR-PET allows mapping of neuronal projections in non-human primate brains, demonstrating the applicability of ecDHFR-based tracking technologies for network monitoring. Finally, we demonstrate the utility of TMP analogs for PET studies of turnover and self-assembly of proteins tagged with ecDHFR mutants. These results establish opportunities for a broad spectrum of previously unattainable PET analyses of mammalian brain circuits at the molecular level.

Colossal barocaloric effects in plastic crystals.

Refrigeration is of vital importance for modern society-for example, for food storage and air conditioning-and 25 to 30 per cent of the world's electricity is consumed for refrigeration1. Current refrigeration technology mostly involves the conventional vapour compression cycle, but the materials used in this technology are of growing environmental concern because of their large global warming potential2. As a promising alternative, refrigeration technologies based on solid-state caloric effects have been attracting attention in recent decades3-5. However, their application is restricted by the limited performance of current caloric materials, owing to small isothermal entropy changes and large driving magnetic fields. Here we report colossal barocaloric effects (CBCEs) (barocaloric effects are cooling effects of pressure-induced phase transitions) in a class of disordered solids called plastic crystals. The obtained entropy changes in a representative plastic crystal, neopentylglycol, are about 389 joules per kilogram per kelvin near room temperature. Pressure-dependent neutron scattering measurements reveal that CBCEs in plastic crystals can be attributed to the combination of extensive molecular orientational disorder, giant compressibility and highly anharmonic lattice dynamics of these materials. Our study establishes the microscopic mechanism of CBCEs in plastic crystals and paves the way to next-generation solid-state refrigeration technologies.

Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab.

BACKGROUND: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. RESULTS: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). CONCLUSION: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.

Efficient Reductive N-11C-Methylation Using Arylamines or Alkylamines and In Situ-Generated [11C]Formaldehyde From [11C]Methyl Iodide.

Reductive N-11C-methylation using [11C]formaldehyde and amines has been used to prepare N-11C-methylated compounds. However, the yields of the N-11C-methylated compounds are often insufficient. In this study, we developed an efficient method for base-free reductive N-11C-methylation that is applicable to a wide variety of substrates, including arylamines bearing electron-withdrawing and electron-donating substituents. A 2-picoline borane complex, which is a stable and mild reductant, was used. Dimethyl sulfoxide was used as the primary reaction solvent, and glacial acetic acid or aqueous acetic acid was used as a cosolvent. While reductive N-11C-methylation efficiently proceeded under anhydrous conditions in most cases, the addition of water to the reductive N-11C-methylation generally increased the yield of the N-11C-methylated compounds. Substrates with hydroxy, carboxyl, nitrile, nitro, ester, amide, and phenone moieties and amine salts were applicable to the reaction. This proposed method for reductive N-11C-methylation should be applicable to a wide variety of substrates, including thermo-labile and base-sensitive compounds because the reaction was performed under relatively mild conditions (70°C) without the need for a base.

Cysts or necrotic components in pancreatic ductal adenocarcinoma is associated with the risk of EUS-FNA/B complications including needle tract seeding.

BACKGROUND: EUS-FNA/B for pancreatic ductal adenocarcinoma (PDAC) is generally considered to be safe; however, while the incidence is low, there are occurrences of complications. Among these complications, there are serious ones like needle tract seeding (NTS), and it is not known than which types of tumors have the risks of EUS-FNA/B complications. This study aimed to evaluate the risk of EUS-FNA/B complications in patients with PDAC, focusing on morphological features. METHODS: Overall, 442 patients who underwent EUS-FNA/B for solid pancreatic masses between January 2018 and May 2022 in four institutions were retrospectively surveyed. Finally, 361 patients histopathologically diagnosed with PDAC were analyzed. Among these patients, 79 tumors with cysts or necrotic components were compared with 282 tumors without cysts or necrotic components. The incidence and risk of EUS-FNA/B complications including NTS were evaluated. RESULTS: There were 9 (2.4 %) of total EUS-FNA/B complications and 3 (0.8 %) of NTS. The incidence of total complication rate and NTS in tumors with cysts or necrotic components were significantly higher than in those without cysts or necrotic components (total complication 6.3 % vs. 1.4 %, p = 0.026, NTS 3.7 % vs. 0 %, p = 0.01). The transgastric route of puncture (OR: 93.3, 95 % CI: 3.81-2284.23) and the existence of cysts or necrotic components (OR: 7.3, 95 % CI: 1.47-36.19) were risk factors for EUS-FNA/B complications identified by the multivariate analysis. CONCLUSIONS: We should pay attention to the risks of EUS-FNA/B complications, including NTS, when the tumor has cysts or necrotic components.

Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

11C-Labeled Radiotracer for Noninvasive and Quantitative Assessment of the Thiocyanate Efflux System in the Brain.

Thiocyanate (SCN-) alters the potency of certain agonists for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and dysfunctions in AMPA receptor signaling are considered to underlie a number of neurological diseases. While humans may be exposed to SCN- from the environment, including food sources, a carrier-mediated system transports SCN- from the brain into the blood and is an important regulator of SCN- distribution in the central nervous system. The assessment of this SCN- efflux system in the brain would thus be useful for understanding the mechanisms underlying the neurotoxicity of SCN- and for elucidating the relationship between the efflux system and brain diseases. However, the currently available technique for studying SCN- efflux is severely limited by its invasiveness. Here, we describe the development of a SCN- protracer, 9-pentyl-6-[11C]thiocyanatopurine ([11C]1), to overcome this limitation. [11C]1 was synthesized by the reaction of the iodo-precursor and [11C]SCN- or the reaction of the disulfide precursor with [11C]NH4CN. The protracer [11C]1 entered the brain after intravenous injection into mice and was rapidly metabolized to [11C]SCN-, which was then eliminated from the brain. The efflux of [11C]SCN- was dose-dependently inhibited by perchlorate, a monovalent anion, and the highest dose caused an 82% reduction in the efflux rate. Our findings demonstrate that [11C]1 can be used for the noninvasive and quantitative assessment of the SCN- efflux system in the brain.

A first-in-human study of 11C-MTP38, a novel PET ligand for phosphodiesterase 7.

PURPOSE: Phosphodiesterase 7 (PDE7) is an enzyme that selectively hydrolyses cyclic adenosine monophosphate, and its dysfunction is implicated in neuropsychiatric diseases. However, in vivo visualization of PDE7 in human brains has hitherto not been possible. Using the novel PET ligand 11C-MTP38, which we recently developed, we aimed to image and quantify PDE7 in living human brains. METHODS: Seven healthy males underwent a 90-min PET scan after injection of 11C-MTP38. We performed arterial blood sampling and metabolite analysis of plasma in six subjects to obtain a metabolite-corrected input function. Regional total distribution volumes (VTs) were estimated using compartment models, and Logan plot and Ichise multilinear analysis (MA1). We further quantified the specific radioligand binding using the original multilinear reference tissue model (MRTMO) and standardized uptake value ratio (SUVR) method with the cerebellar cortex as reference. RESULTS: PET images with 11C-MTP38 showed relatively high retentions in several brain regions, including in the striatum, globus pallidus, and thalamus, as well as fast washout from the cerebellar cortex, in agreement with the known distribution of PDE7. VT values were robustly estimated by two-tissue compartment model analysis (mean VT = 4.2 for the pallidum), Logan plot, and MA1, all in excellent agreement with each other, suggesting the reversibility of 11C-MTP38 binding. Furthermore, there were good agreements between binding values estimated by indirect method and those estimated by both MRTMO and SUVR, indicating that these methods could be useful for reliable quantification of PDE7. Because MRTMO and SUVR do not require arterial blood sampling, they are the most practical for the clinical use of 11C-MTP38-PET. CONCLUSION: We have provided the first demonstration of PET visualization of PDE7 in human brains. 11C-MTP38 is a promising novel PET ligand for the quantitative investigation of central PDE7.

Relevance of hydrogen bonded associates to the transport properties and nanoscale dynamics of liquid and supercooled 2-propanol.

2-Propanol was investigated, in both the liquid and supercooled states, as a model system to study how hydrogen bonds affect the structural relaxation and the dynamics of mesoscale structures, of approximately several Ångstroms, employing static and quasi-elastic neutron scattering and molecular dynamics simulation. Dynamic neutron scattering measurements were performed over an exchanged wave-vector range encompassing the pre-peak, indicative of the presence of H-bonding associates, and the main peak. The dynamics observed at the pre-peak is associated with the formation and disaggregation of the H-bonded associates and is measured to be at least one order of magnitude slower than the dynamics at the main peak, which is identified as the structural relaxation. The measurements indicate that the macroscopic shear viscosity has a similar temperature dependence as the dynamics of the H-bonded associates, which highlights the important role played by these structures, together with the structural relaxation, in defining the macroscopic rheological properties of the system. Importantly, the characteristic relaxation time at the pre-peak follows an Arrhenius temperature dependence whereas at the main peak it exhibits a non-Arrhenius behavior on approaching the supercooled state. The origin of this differing behavior is attributed to an increased structuring of the hydrophobic domains of 2-propanol accommodating a more and more encompassing H-bond network, and a consequent set in of dynamic cooperativity.

Theoretical and Experimental Investigation of the Effect of Pump Laser Frequency Fluctuations on Signal-to-Noise Ratio of Brillouin Dynamic Grating Measurement with Coherent FMCW Reflectometry.

Signal-dependent speckle-like noise has constituted a serious factor in Brillouin-grating based frequency-modulated continuous-wave (FMCW) reflectometry and it has been indispensable for improving the signal-to-noise ratio (S/N) of the Brillouin dynamic grating measurement to clarify the noise generation mechanism. In this paper we show theoretically and experimentally that the noise is generated by the frequency fluctuations of the pump light from a laser diode (LD). We could increase the S/N from 36 to 190 merely by driving the LD using a current source with reduced technical noise. On the basis of our experimental result, we derived the theoretical formula for S/N as a function of distance, which contained the second and fourth-order moments of the frequency fluctuations, by assuming that the pump light frequency was modulated by the technical noise. We calculated S/N along the 1.35 m long optical fiber numerically using the measured power spectral density of the frequency fluctuations, and the resulting distributions agreed with the measured values in the 10 to 190 range. Since higher performance levels are required if the pump light source is to maintain the S/N as the fiber length increases, we can use the formula to calculate the light source specifications including the spectral width and rms value of the frequency fluctuations to achieve a high S/N while testing a fiber of a given length.

Development of an In Vivo Method to Estimate Effective Drug Doses and Quantify Fatty Acid Amide Hydrolase in Rodent Brain using Positron Emission Tomography Tracer [11C]DFMC.

Fatty acid amide hydrolase (FAAH) is a key enzyme in the endocannabinoid system. N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC) was developed as an irreversible-type positron emission tomography (PET) tracer for FAAH. Here, we attempted to noninvasively estimate rate constant k3 (rate of transfer to the specifically-bound compartment) as a direct index for FAAH in the rat brain. First, the two-tissue compartment model analysis including three parameters [K1-k3, two-tissue compartment model for the irreversible-type radiotracer (2TCMi)] in PET study with [11C]DFMC was conducted, which provided 0.21 ± 0.04 ml·cm-3·min-1 of the net uptake value (Ki), an indirect index for FAAH, in the FAAH-richest region (the cingulate cortex). Subsequently, to noninvasively estimate Ki value, the reference model analysis (Patlak graphical analysis reference model) was tried using a time-activity curve of the spinal cord. In that result, the noninvasive Ki value (KREF) was concisely estimated with high correlation (r > 0.95) to Ki values based on 2TCMi. Using estimated KREF value, we tried to obtain calculated-k3 based on previously defined equations. The calculated k3 was successfully estimated with high correlation (r = 0.95) to direct k3 in 2TCMi. Finally, the dose relationship study using calculated k3 demonstrated that in vivo ED50 value of [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate, a major inhibitor of FAAH, was 66.4 µg/kg in rat brain. In conclusion, we proposed the calculated k3 as an alternative index corresponding to regional FAAH concentrations and suggested that PET with [11C]DFMC enables occupancy study for new pharmaceuticals targeting FAAH. SIGNIFICANCE STATEMENT: In the present study, we proposed calculated k3 as an alternative index corresponding with fatty acid amide hydrolase concentration. By using calculated k3, in vivo ED50 of [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate was successfully estimated to be 66.4 µg/kg for rats. Thus, we demonstrated the pharmacological utility of positron emission tomography with N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide.

Correction to: Radiopharmaceutical tracers for cardiac imaging.

Regrettably the original version of the above article contained errors in the three chemical structures presented in the 'Atherosclerosis imaging' section of Table 5, namely: 99mTc annexin V, 68Ga DOTATATE, and 64Cu DOTATATE; the chemical structures have been corrected in Table presented here. In addition, the radiopharmaceutical for isotope 67Ga has been corrected to 67Ga citrate, and many of the radiopharmaceuticals presented at the end of the table have been corrected.

Radiopharmaceutical tracers for cardiac imaging.

Cardiovascular disease (CVD) is the leading cause of death and disease burden worldwide. Nuclear myocardial perfusion imaging with either single-photon emission computed tomography or positron emission tomography has been used extensively to perform diagnosis, monitor therapies, and predict cardiovascular events. Several radiopharmaceutical tracers have recently been developed to evaluate CVD by targeting myocardial perfusion, metabolism, innervation, and inflammation. This article reviews old and newer used in nuclear cardiac imaging.

Long-term course of inflammatory bowel disease after the Great East Japan Earthquake.

BACKGROUND AND AIM: This study analyzed inflammatory bowel disease activity for 2 years after the Great East Japan Earthquake. METHODS: We compared the relapse rates of patients with ulcerative colitis or Crohn's disease 1 and 2 years after the earthquake with rates immediately after the earthquake. To evaluate continuous disease courses, we also performed multivariate time-to-event analyses from the time of the earthquake to the onset of additional treatments. RESULTS: Of 903 patients with ulcerative colitis or Crohn's disease in our previous study, we could evaluate 2-year courses in 677 patients (394 ulcerative colitis and 283 Crohn's disease). Compared with the relapse rates of ulcerative colitis and Crohn's disease immediately after the earthquake (15.8% and 7.0%, respectively), those in the corresponding periods in 2012 (2.5% and 1.1%, respectively) and 2013 (2.3% and 2.5%, respectively) significantly decreased. There were 226 patients who required additional treatments after the earthquake. Multivariate time-to-event analyses revealed that only patients who had experienced the death of family members or friends were likely to need additional treatments (hazard ratio = 1.77, 95% confidence interval = 1.25-2.47). No other factors had a significant influence. CONCLUSIONS: The relapse rates 1 and 2 years after the earthquake significantly decreased. The factors that influenced long-term relapse were different from those that influenced short-term relapse.

Survey of Exposure Dose during Percutaneous Coronary Intervention for Chronic Total Occlusion.

During percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), longer fluoroscopic time as compared with PCI for non-CTO lesions may cause skin injury by increased radiation. We have performed a multi-center observational study comparing the exposed dose during the PCI of CTO (CTO group) and during the PCI of non-CTO lesions (non-CTO group). Exposure doses were assessed in 313 patients with CTO and 3,310 patients with non-CTO lesions. Total fluoroscopy time (59.0 ±35.5 vs 26.8 ±18.8 min, p<0.0001) and the total air kerma (2.76±2.11 vs 1.27±0.94 Gy, p<0.0001) were significantly greater in the CTO group than in the non-CTO group. The maximum air kerma of the CTO group was 13.62 Gy. Informed consent about the risk of transient depilation and the transient erythema is required for the case with radiation dose over 3 Gy. The frequency of the patient who received radiation >3 Gy was significantly higher in the CTO group as compared with the non-CTO group (34.1% vs 4.9%). Therefore, informed consent before an operation and postoperative follow-up are indispensable for the performed PCI of CTO. Moreover, comprehensive understanding of the exposure dose during operation and to record the final exposure dose may be extremely important for the radiological technologists.

Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone.

BACKGROUND INFORMATION: Cortactin contributes to growth cone morphogenesis by forming with dynamin, ring-shaped complexes that mechanically bundle and stabilise F-actin. However, the regulatory mechanism of cortactin action is poorly understood. RESULTS: Immunofluorescence microscopy revealed that protein kinase C (PKC) α colocalises with cortactin at growth cone filopodia in SH-SY5Y neuroblastoma cells. PKC activation by phorbol 12-myristate 13-acetate causes cortactin phosphorylation, filopodial retraction and F-actin-bundle loss. Moreover, PKCα directly phosphorylates cortactin in vitro at S135/T145/S172, mitigating both cortactin's actin-binding and actin-crosslinking activity, whereas cellular expression of a phosphorylation-mimetic cortactin mutant hinders filopodial formation with a significant decrease of actin bundles. CONCLUSIONS: Our results indicate that PKC-mediated cortactin phosphorylation might be implicated in the maintenance of growth cone.

Internal dynamics of F-actin and myosin subfragment-1 studied by quasielastic neutron scattering.

Various biological functions related to cell motility are driven by the interaction between the partner proteins, actin and myosin. To obtain insights into how this interaction occurs, the internal dynamics of F-actin and myosin subfragment-1 (S1) were characterized by the quasielastic neutron scattering measurements on the solution samples of F-actin and S1. Contributions of the internal motions of the proteins to the scattering spectra were separated from those of the global macromolecular diffusion. Analysis of the spectra arising from the internal dynamics showed that the correlation times of the atomic motions were about two times shorter for F-actin than for S1, suggesting that F-actin fluctuates more rapidly than S1. It was also shown that the fraction of the immobile atoms is larger for S1 than for F-actin. These results suggest that F-actin actively facilitates the binding of myosin by utilizing the more frequent conformational fluctuations than those of S1.

Improved synthesis of 6-bromo-7-[11C]methylpurine for clinical use.

BACKGROUND: Multidrug resistance-associated protein 1 (MRP1), an energy-dependent efflux pump, is expressed widely in various tissues and contributes to many physiological and pathophysiological processes. 6-Bromo-7-[11C]methylpurine ([11C]7m6BP) is expected to be useful for the assessment of MRP1 activity in the human brain and lungs. However, the radiochemical yield (RCY) in the synthesis of [11C]7m6BP was low, limiting its clinical application, because the methylation of the precursor with [11C]CH3I provided primarily the undesired isomer, 6-bromo-9-[11C]methylpurine ([11C]9m6BP). To increase the RCY of [11C]7m6BP, we investigated conditions for improving the [11C]7m6BP/[11C]9m6BP selectivity of the methylation reaction. RESULTS: [11C]7m6BP was manually synthesized via the methylation of 6-bromopurine with [11C]CH3I in various solvents and at different temperatures in the presence of potassium carbonate for 5 min. Several less polar solvents, including tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), and ethyl acetate (AcOEt) improved the [11C]7m6BP/[11C]9m6BP selectivity from 1:1 to 2:1, compared with the conventionally used solvents for the alkylation of 6-halopurines, acetone, acetonitrile, and N,N-dimethylformamide. However, a higher temperature (140 °C or 180 °C) was needed to progress the 11C-methylation in the less polar solvents, and the manual conditions could not be directly translated to an automated synthesis. [11C]Methyl triflate ([11C]CH3OTf) was thus used as a methylating agent to increase the conversion at a lower temperature. The 11C-methylation using [11C]CH3OTf at 100 °C proceeded efficiently in THF, 2-MeTHF, and AcOEt with maintenance of the improved selectivity. Starting from 28 to 34 GBq [11C]CO2, [11C]7m6BP was produced with 2.3-2.6 GBq for THF, 2.7-3.3 GBq for AcOEt, and 2.8-3.9 GBq for 2-MeTHF at approximately 30 min after the end of bombardment (n = 3 per solvent). The isolated RCYs (decay corrected) for THF, 2-MeTHF, and AcOEt were 24-28%, 29-35%, and 22-31% (n = 3), respectively. CONCLUSIONS: The use of THF, 2-MeTHF, and AcOEt improved the [11C]7m6BP/[11C]9m6BP selectivity in the methylation reaction, and the improved method provided [11C]7m6BP with sufficient radioactivity for clinical use.

A case of rapidly progressive glomerulonephritis with double-positive anti-GBM antibody and MPO-ANCA after SARS-CoV-2 vaccination and relapse during 1 year follow-up.

Although mRNA vaccines for COVID-19 are highly beneficial and are recommended for patients with kidney disease, adverse reactions in some patients after vaccination have been problematic. Various vasculitis and renal disorders have been reported after vaccination; however, a causal relationship has not yet been identified. In this report, we describe a case of rapidly progressive glomerulonephritis that developed after SARS-CoV-2 vaccination, in which both anti-glomerular basement membrane (anti-GBM) and myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) were present. The patient's renal biopsy showed that of the 48 glomeruli in total, four showed global sclerosis and none showed segmental sclerosis. The biopsy showed 11 cellular glomerular crescents and 5 fibrocellular glomerular crescents. Renal function improved with steroids, rituximab, and plasma exchange. Approximately 9 months later, MPO-ANCA was again elevated, and the pulmonary lesions worsened, again requiring multidisciplinary treatment. This case suggests that caution should be exercised in the development of double-positive disease after vaccination, and that long-term observation may be necessary because of the possibility of relapse.