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Background: Rare cases of de novo or relapsed kidney diseases associated with vaccination against coronavirus disease 2019 (COVID-19) have been increasingly reported. The aim of this study was to report the incidence, etiologies, and outcomes of acute kidney disease (AKD) following COVID-19 vaccination. Methods: This retrospective study extracted cases from renal registry of a single medical center from 1 March 2021 to 30 April 2022, prior to the significant surge in cases of the Omicron variant of COVID-19 infection in Taiwan. Adult patients who developed AKD after COVID-19 vaccination were included. We utilized the Naranjo score as a causality assessment tool for adverse vaccination reactions and charts review by peer nephrologists to exclude other causes. The etiologies, characteristics, and outcomes of AKD were examined. Results: Twenty-seven patients (aged 23 to 80 years) with AKD were identified from 1,897 vaccines (estimated rate of 13.6 per 1000 patient-years within the renal registry). A majority (77.8%) of vaccine received messenger RNA-based regimens. Their median (IQR) Naranjo score was 8 (6-9) points, while 14 of them (51.9%) had a definite probability (Naranjo score ≥ 9). The etiologies of AKD included glomerular disease (n = 16) consisting of seven IgA nephropathy, four anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN), three membranous glomerulonephritis, two minimal change diseases, and chronic kidney disease (CKD) with acute deterioration (n = 11). Extra-renal manifestations were found in four patients. Over a median (IQR) follow-up period of 42 (36.5-49.5) weeks, six patients progressed to end-stage kidney disease (ESKD). Conclusion: Besides glomerulonephritis (GN), the occurrence of AKD following COVID-19 vaccination may be more concerning in high-risk CKD patients receiving multiple doses. Patients with the development of de novo AAN, concurrent extra-renal manifestations, or pre-existing moderate to severe CKD may exhibit poorer kidney prognosis.
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Patients with advanced chronic kidney disease (CKD) often present with skeletal abnormalities, a condition known as renal osteodystrophy (ROD). While tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 are critical for bone mineralization, their role in the etiology of ROD is unclear. To address this, ROD was induced in both WT and Phospho1 knockout (P1KO) mice through dietary adenine supplementation. The mice presented with hyperphosphatemia, hyperparathyroidism, and elevated levels of FGF23 and bone turnover markers. In particular, we noted that in CKD mice, bone mineral density (BMD) was increased in cortical bone (P < 0.05) but decreased in trabecular bone (P < 0.05). These changes were accompanied by decreased TNAP (P < 0.01) and increased PHOSPHO1 (P < 0.001) expression in WT CKD bones. In P1KO CKD mice, the cortical BMD phenotype was rescued, suggesting that the increased cortical BMD of CKD mice was driven by increased PHOSPHO1 expression. Other structural parameters were also improved in P1KO CKD mice. We further investigated the driver of the mineralization defects, by studying the effects of FGF23, PTH, and phosphate administration on PHOSPHO1 and TNAP expression by primary murine osteoblasts. We found both PHOSPHO1 and TNAP expressions to be downregulated in response to phosphate and PTH. The in vitro data suggest that the TNAP reduction in CKD-MBD is driven by the hyperphosphatemia and/or hyperparathyroidism noted in these mice, while the higher PHOSPHO1 expression may be a compensatory mechanism. Increased PHOSPHO1 expression in ROD may contribute to the disordered skeletal mineralization characteristic of this progressive disorder.
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Distúrbio Mineral e Ósseo na Doença Renal Crônica , Hiperfosfatemia , Monoéster Fosfórico Hidrolases , Insuficiência Renal Crônica , Animais , Densidade Óssea/fisiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Distúrbio Mineral e Ósseo na Doença Renal Crônica/genética , Hiperfosfatemia/complicações , Camundongos , Camundongos Knockout , Fosfatos , Monoéster Fosfórico Hidrolases/metabolismo , Insuficiência Renal Crônica/genéticaRESUMO
Transforming growth factor ß1 (TGF-ß1) is a known regulator of chondrocyte proliferation and promotes cartilage repair in osteoarthritis (OA). microRNA-29b-3p (miR-29b-3p) is downregulated by TGF-ß1 and overexpressed in OA cartilage. However, the ability of miR-29b-3p to mediate the chondrocyte pro-proliferative effects of TGF-ß1 is not yet understood. This current study aimed to investigate the effect of miR-29b-3p on TGF-ß1-induced cell proliferation in murine articular chondrocytes. The stimulation of chondrocytes by TGF-ß1 for 24 h resulted in the downregulation of miR-29b-3p expression. The ratio of G0/G1 phase cells decreased in response to TGF-ß1 whereas the ratio of S phase cells was increased. Consistent with this observation, miR-29b-3p overexpression inhibited TGF-ß1's ability to promote the ratio of S phase cells and downregulate the ratio of G0/G1 phase cells. These findings suggest that the downregulation of miR-29b-3p is a likely requirement for TGF-ß1-mediated proliferation of murine articular chondrocytes. Furthermore, implying that miR-29b-3p expression may be involved in reduced chondrocyte proliferation in OA.
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Biomineralization is a fundamental process key to the development of the skeleton. The phosphatase orphan phosphatase 1 (PHOSPHO1), which likely functions within extracellular matrix vesicles, has emerged as a critical regulator of biomineralization. However, the biochemical pathways that generate intravesicular PHOSPHO1 substrates are currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6) is an upstream source of the PHOSPHO1 substrate. To test this, we characterized skeletal phenotypes of mice homozygous for a targeted deletion of Enpp6 (Enpp6 -/- ). Micro-computed tomography of the trabecular compartment revealed transient hypomineralization in Enpp6 -/- tibias (p < 0.05) that normalized by 12 weeks of age. Whole-bone cortical analysis also revealed significantly hypomineralized proximal bone in 4- but not 12-week-old Enpp6 -/- mice (p < 0.05) compared with WT animals. Back-scattered SEM revealed a failure in 4-week-old trabecular bone of mineralization foci to propagate. Static histomorphometry revealed increased osteoid volume (p > 0.01) and osteoid surface (p < 0.05), which recovered by 12 weeks but was not accompanied by changes in osteoblast or osteoclast number. This study is the first to characterize the skeletal phenotype of Enpp6 -/- mice, revealing transient hypomineralization in young animals compared with WT controls. These data suggest that ENPP6 is important for bone mineralization and may function upstream of PHOSPHO1 as a novel means of generating its substrates inside matrix vesicles. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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INTRODUCTION: Nontraumatic acute abdomen (NTAA) in dialysis patients is a challenging issue. The aetiologies of NTAA vary considerably depending on the renal replacement therapy (RRT) modality. Although haematological parameters and contributing factors have been reported to be associated with outcomes for dialysis patients, their clinical effect on the length of hospital stay (LOS) remains unknown. METHODS: We retrospectively analysed 52 dialysis patients (peritoneal dialysis [PD], n = 33; haemodialysis [HD], n = 19) and 30 non-dialysis patients (as controls) between January 2011 and December 2014. To attenuate the selection bias, non-dialysis patients with NTAA were matched to cases at a ratio of 1:1 by age, gender and comorbidities (diabetes mellitus and hypertension). Their demographic characteristics, laboratory data, clinical assessment scores and LOS were analysed. RESULTS: The PD group exhibited a significantly higher neutrophil percentage, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR); longer LOS; and lower lymphocyte percentage and absolute lymphocyte count than the control group. After multivariate analysis adjustment, female gender, longer RRT duration and higher intact parathyroid hormone (iPTH) levels were associated with a lower probability of being discharged home. In the dialysis group, a higher iPTH level (> 313 µg/mL) was positively correlated with longer LOS. iPTH level combined with NLR can be used as a surrogate marker for predicting longer LOS (p < 0.001). CONCLUSION: NTAA dialysis patients with female gender, longer RRT duration and higher iPTH levels are prone to experiencing longer LOS. In addition, the combination of iPTH and NLR is a significant determinant for LOS in NTAA dialysis patients.
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Abdome Agudo , Feminino , Humanos , Tempo de Internação , Contagem de Linfócitos , Linfócitos , Neutrófilos , Diálise Renal , Estudos RetrospectivosRESUMO
OBJECTIVE: Although proteinuria has been increasingly reported in lung cancers, especially small cell lung cancer (SCLC), its clinical impact in patients with SCLC remains unknown. MATERIALS AND METHODS: We analyzed patients with newly-diagnosed SCLC confirmed by clinical, radiological, and pathological features over a 7-year period. Pretreatment proteinuria was assessed by quantitative analysis of 24-h urine before receiving chemotherapy. The demographic, laboratory characteristics and its impact on survival outcome were evaluated. RESULTS: There were 140 SCLC patients with the mean age of 70.2 years, extensive stage (89.3%), and male predominance (81.4%). Significant proteinuria (>300 mg/day) occurred in 17.4% (24/140) patients. Patients with proteinuria had significant higher serum blood urea nitrogen, lower total calcium, total protein, albumin levels, and lower creatinine clearance (Ccr) (24-h Ccr). Daily protein excretion was negatively correlated with serum total protein, albumin, and Ccr. Using a multivariable Cox proportional hazard model, proteinuria (hazard ratio, 1.943, 95% confidence interval 1.148-3.259, P = 0.010), along with poor performance status and serum albumin, were independent risk factors of all-cause mortality. Proteinuria was also associated with poor survival status (6.08 vs. 11.88 months, P < 0.001), especially in those who had severe proteinuria (>2 g/day). CONCLUSIONS: Proteinuria is not uncommon and associated with all-cause mortality in patients with SCLC.
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Proteínas Sanguíneas/genética , Proteinúria/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteinúria/epidemiologia , Proteinúria/genética , Proteinúria/patologia , Fatores de Risco , Albumina Sérica/genética , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
Myeloma-associated kidney disease (MRKD) occurs in ≤40% patients with multiple myeloma (MM). The impact of hemodialysis (HD) on patients with MM was investigated. Between 2000 and 2010, a total of 1,610 patients in Taiwan were enrolled from the National Health Institute Research Database. MM was an independent risk factor for HD following adjustment via multivariate logistic regression analysis (adjusted hazard ratio, 7.347; 95% confidence interval, 6.156-8.768; log-rank test, P<0.001). In addition, a notable decrease in survival rate was determined in patients with MM who underwent HD in the first year since diagnosis of MM. A total of 198 (61.49%) patients received HD in the first year. Patients with MM with a lower frequency of HD in the first year had a relatively good prognosis. The present study confirmed that MM was a risk factor for HD. Significant early mortality in the first year was determined in patients with MM who underwent HD; however, renal recovery following therapeutic management was a prognostic factor. In addition to anti-myeloma therapy, early initiation of HD was beneficial following risk stratification of MRKD; however, an increased probability of recovery of renal function and discontinuation of dialysis, was demonstrated in patients with MM following HD, compared with patients with MM without HD.
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In this retrospective cohort study based in Taiwan, we reported the current epidemiology of patients with multiple myeloma and analyzed the factors affecting mortality. We identified 7285 patients with newly diagnosed multiple myeloma (MM) between 1997 and 2013 in Taiwan. Privileges data from the National Health Institute Research Database was used, as it is made readily available to the public in electronic format for research purposes. From 1997 to 2013, the average incidence of MM per 100,000 people was 1.83. The mortality accounted for an average of 0.44 per 100,000 deaths. In all 7285 inpatients with MM, the proportion of male patients was greater than that of female (59.90% vs. 40.10%); the mean age was 68.71 years with the proportion of those >55 years of age was 85.11%; and the proportion of a catastrophic illness was 66.51%. The death risk of the inpatient dialysis group was 3.044 times that of patients without dialysis (P <0.001). Moreover, the risk of death to men in the hospital setting was 1.162 times that of women (P = 0.012), and in the group of patients aged >55 years, the risk of in-hospital death was 1.511 times more than that in those aged ≤55 years (P <0.001). The risk of hospital death due to catastrophic illness was 1.347 times that of a non-catastrophic illness (P <0.001). Male patients and those >55 years of age had the most common prevalence of MM in Taiwan. Hemodialysis treatment, male sex, old age, and catastrophic illness were independent predictors of hospital mortality in patients with MM.
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Mieloma Múltiplo/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Mieloma Múltiplo/mortalidade , Vigilância da População , Prevalência , Sistema de Registros , Fatores de Risco , Fatores Socioeconômicos , Taiwan/epidemiologiaRESUMO
OBJECTIVE: To compare the dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) using the simultaneous integrated boost (SIB) technique with that of the traditional midline block (MB) technique for boosting the parametrium in patients with cervical cancer. METHODS: Treatment plans using VMAT or IMRT with the SIB technique (VMAT-SIB and IMRT-SIB) and IMRT followed by the MB technique (IMRT-MB) were generated for each of the 10 patients with cervical cancer. For the SIB plans, 45-Gy and 50-Gy dose levels in 25 equal fractions were set for the pelvis planning target volume 45 (PTV45) and the parametrial boost volume (PTV50), respectively. For the IMRT-MB plans, the parametrium was sequentially boosted with the MB technique (5.4 Gy in three fractions) after pelvic IMRT (PTV45). RESULTS: Volume receiving 100% of the prescribed dose or more coverage of the PTV50 was significantly better for VMAT-SIB and IMRT-SIB than that for IMRT-MB (99.08 and 99.31% compared with 91.79%, respectively; p < 0.05). VMAT-SIB and IMRT-SIB both generated significantly greater doses to the organs at risk (OARs) except for the volume receiving 50 Gy or more doses, which were significantly lower for the bladder and bowel. Comparable results were achieved with VMAT-SIB and IMRT-SIB. CONCLUSION: The VMAT-SIB and IMRT-SIB techniques are promising in terms of dose distributions and tumour coverage, although these approaches might result in slightly higher doses of radiation to the OARs. Advances in knowledge: This is the first study to examine the feasibility of the SIB technique using IMRT or VMAT to boost the parametrium. The techniques dosimetrically produced better target coverage but resulted in slightly higher doses to the OARs.
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Colo do Útero/efeitos da radiação , Peritônio/efeitos da radiação , Radioterapia de Intensidade Modulada/métodos , Neoplasias do Colo do Útero/radioterapia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
CASE: A 73-year-old man with Dukes' C adenocarcinoma of the rectum, pT3N2bM0, stage IIIB, presented with voiding difficulties including poor stream and terminal dribbling for one month. The patient was under careful surveillance and had no postoperative recurrence. Physical examination revealed a palpable irregular nodular lesion (0.5 × 0.5 cm(2)) at the penile-scrotal junction. He underwent urethroscopy, which showed a cauliflower lesion in the pendulous urethra. Transurethral resection was performed and histopathologic and immunochemical staining demonstrated a metastatic moderately differentiated urethral adenocarcinoma from the colorectal primary. OUTCOME: His voiding disorder improved significantly post-operation and he commenced second-line chemotherapy combined with regional radiotherapy. Follow-up urethrocystoscopy and abdominal computed tomography demonstrated no recurrence or metastatic disease. His tumor marker remained within the normal range for 12 months. CONCLUSION: Urethral metastasis from primary colon cancer is extremely rare. This disease, with its various atypical presentations, presents a diagnostic challenge to the clinician. In patients with recurrent or persistent lower urinary tract symptoms, further urologic workup including thorough history taking, physical examination, and imaging surveys is warranted.
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Adenocarcinoma/patologia , Neoplasias Retais/patologia , Neoplasias Uretrais/secundário , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Idoso , Humanos , Masculino , Neoplasias Uretrais/cirurgia , Neoplasias Uretrais/terapiaRESUMO
Renal failure is a common morbidity in multiple myeloma (MM). Although proteinuria has been increasingly reported in malignancies, it is not routinely used to refine risk estimates of survival outcomes in patients with MM. Here we aimed to investigate initial serum albumin and 24-hour daily protein excretion (24-h DPE) before treatment as prognostic factors in patients with MM. We conducted a retrospective analysis of 102 patients with myeloma who were ineligible for haematopoietic stem cell transplantation between October 2000 and December 2012. Initial proteinuria was assessed before treatment by quantitative analysis of 24-hour urine samples. The demographic and laboratory characteristics, survival outcome, and significance of pre-treatment 24-h DPE and albumin in the new staging system of MM were analyzed. Pre-treatment proteinuria (>300 mg/day) was present in 66 patients (64.7%). The optimal cut-off value of 24-h DPE before treatment was 500 mg/day. Analysis of the time-dependent area under the curve showed that the serum albumin and 24-h DPE before treatment were better than 24-h creatinine clearance rate and ß2-microglobulin. A subgroup analysis showed that an initial excess proteinuria (24-h DPE ≥ 500 mg) was associated with poor survival status (17.51 vs. 34.24 months, p = 0.002). Furthermore, initial serum albumin was an independent risk factor on multivariate analysis (<2.8 vs. ≥ 2.8, hazard ratio = 0.486, p = 0.029). Using the A-DPE staging system, there was a significant survival difference among patients with stage I, II, and III MM (p < 0.001). Initial serum albumin and 24-h DPE before treatment showed significant prognostic factors in patients with MM, and the new A-DPE staging system may be utilized instead of the International Staging System. Its efficacy should be evaluated by further large prospective studies.
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Mieloma Múltiplo/sangue , Mieloma Múltiplo/urina , Proteinúria/complicações , Albumina Sérica/metabolismo , Idoso , Feminino , Humanos , Masculino , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Fatores de TempoRESUMO
A 33-year-old Chinese man with 9-year history of Kimura's disease (KD) was admitted with a 1-month history of recurrent claudication. He did not have any clinical discomfort and had not taken any preventive medication in the past. He accepted percutaneous transluminal angioplasty and the pathologic diagnosis was reportedly consistent with necrotizing eosinophilic vasculitis. This is the rare reported case of KD associated necrotizing eosinophilic vasculitis presenting with recurrent peripheral arterial occlusive disease and the difficulties encountered in establishing an accurate diagnosis with unusual presentations. This case also highlights the possibility of recurrent complications without aggressive medical treatment in such unusual eosinophilic disorders.
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Hiperplasia Angiolinfoide com Eosinofilia , Síndrome de Churg-Strauss , Doença Arterial Periférica , Adulto , Hiperplasia Angiolinfoide com Eosinofilia/complicações , Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico por imagem , Hiperplasia Angiolinfoide com Eosinofilia/terapia , Angioplastia , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/diagnóstico por imagem , Síndrome de Churg-Strauss/terapia , Humanos , Masculino , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , RadiografiaRESUMO
The outcomes of matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA) remain controversial. The clinical outcome in patients that undergo transplantation following failed IST is typically poorer when compared with patients that initially underwent transplantation. Clinical treatment algorithms have been proposed to determine the management of such patients, and account for individual conditions, personal preferences and prognostic risk factors. The present study reports the promising outcome of a 22-year-old patient exhibiting SAA. The patient underwent peripheral blood stem cell transplantation (PBSCT) from an MUD using a fludarabine-based conditioning regimen and low-dose total body irradiation as an alternative method to first-line IST. The patient achieved rapid bone marrow reconstitution and has been in complete remission for 32 months. The aim of the fludarabine-based conditioning regimen with PBSCT was to improve the patient's therapeutic outcome and provide a convenient treatment strategy. Furthermore, this regimen extends the application of HSCT to patients who are older or those that are without a matched related donor.
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The formation of spinal epidural abscess following acupuncture is very rare. We herein report the case of a 54-year-old woman who presented with progressive low back pain and fever with a root sign. She underwent surgical decompression, with an immediate improvement of the low back pain. A culture of the epidural abscess grew Serratia marcescens. One year postoperatively, magnetic resonance imaging revealed the almost complete eradication of the abscess. This case is the first case of Serratia marcescens-associated spinal epidural abscess formation secondary to acupuncture. The characteristics of spinal epidural abscess that develop after acupuncture and how to prevent such complications are also discussed.