Association of post-treatment hypoalbuminemia and survival in Chinese patients with metastatic renal cell carcinoma

Background: Hypoalbuminemia adversely affects the clinical outcomes of various cancers. The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3–5 weeks after treatment in patients with metastatic renal cell carcinoma (mRCC) who received sorafenib or sunitinib as first-line treatment. Methods: In this single-center, retrospective study, we assessed the progression-free survival (PFS) and overall sur-vival (OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment. PFS and OS were compared between patients with post-treatment hypoalbuminemia (post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level (albumin level ≥36.4 g/L). The Memorial Sloan Kettering Cancer Center (MSKCC)risk model stratified mRCC patients into three risk categories. Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models. Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis. Results: The median PFS and OS of the 184 patients were 11 months (95% confidence interval [CI] 9–12 months) and 23 months (95% CI 19–33 months), respectively. Patients with post-treatment hypoalbuminemia had significantly shorter median PFS (6 months [95% CI 5–7 months]) and OS (11 months [95% CI 9–15 months]) than patients who had normal post-treatment albumin levels (PFS: 12 months [95% CI 11–16 months], P < 0.001; OS: 31 months [95% CI 24–42 months], P < 0.001), respectively. Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS (hazard ratio [HR], 2.113; 95% CI 1.390–3.212; P < 0.001) and OS (HR, 2.388; 95% CI 1.591–3.585; P < 0.001). Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS. The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS (c-index: 0.68 and 0.73, respectively) compared with the basic MSKCC risk model (c-index: 0.67 and 0.70, respectively). The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis (both P < 0.001). Conclusions: Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors. Additionally, integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.     

Differences between the Measured and Calculated Free Serum Phenytoin Concentrations in Epileptic Patients

Purpose

The pharmacokinetics of phenytoin is complicated by genetic and environmental differences. It is, therefore, important to monitor the serum concentrations in patients who receive phenytoin. Because most of the phenytoin in serum is bound to proteins, the level of serum albumin influences the amount of free phenytoin.

Materials and Methods

We compared the measured and calculated free phenytoin levels in epileptic patients who were taking phenytoin monotherapy, using the Sheiner-Tozer equation. A total of 49 patients (30 men and 19 women; age range, 15 - 87 years) were included in the study and their trough serum phenytoin and albumin concentrations were analyzed.

Results

The linear correlation between free and total phenytoin concentrations was moderate (r = 0.822, p < 0.001). The mean difference between measured and calculated free phenytoin was large (0.65 ± 0.88 µg/mL; 95% confidence interval (CI), -1.11 to 2.41). After dividing the patients into groups by albumin concentration, hypoalbuminemic patients (< 3.5 g/dL) more often had a greater percent difference (≥ 20%) than observed in the normoalbuminemic (≥ 3.5 g/dL) group.

Conclusion

In hypoalbuminemic patients, the measurement of free phenytoin level is necessary to properly evaluate the phenytoin level than that calculated from total phenytoin level.     

A case report of congenital nephrotic syndrome caused by new mutations of NPHS1

Congenital nephrotic syndrome (CNS) is a rare autosomal recessive disorder that occurs in the first 0 to 3 months of life. The course of CNS is progressive, often leading to end-stage renal disease within 2 to 3 years. Most patients with CNS are resistant to glucocorticoids and immunosuppressive drugs. We report a girl aged 1 month and 20 days who was admitted to hospital with a history of abdominal distension and palpebral edema. She was diagnosed with CNS and administered a glucocorticoid (methylprednisolone) for 2 years. Targeted high-throughput next-generation sequencing showed mutations in the NPHS1 gene. She had a favorable outcome after 2 years of treatment. She has remained in complete remission for the last 6 months. From a clinical point of view, the outcome of CNS may be associated with end-stage renal disease or even death. Appropriate pharmacotherapy is beneficial to maintain a normal function and integrity of the glomerular barrier. An aggressive treatment plan is required to save the life of patients with CNS, even if a heterozygous mutation is detected by genetic analysis.     

低蛋白血症和骨折、骨质疏松相关性研究

低蛋白血症是一种由多种原因引起的临床综合征,重度低蛋白血症因与病情严重程度及预后密切相关而被广泛研究。但低蛋白血症往往多为慢性过程,病因复杂,起病隐匿,易被临床医生忽视。近来,越来越多的学者指出低蛋白血症、骨折与骨质疏松之间具有相关性,对其发生机制也从多方面进行了研究。虽然目前对低蛋白血症、骨折与骨质疏松的研究不断深入,但对其认识依然欠缺。本文将通过对低蛋白血症、骨折与骨质疏松相关性研究进行综述,旨在为骨折预防及其危险因素的评估、骨质疏松的干预措施提供新的思路。     

Microsporum ferrugineum infection with unusual clinical features

Unusual skin manifestations of a dermatophyte infection in a 30-year-old female were reported. These included a remarkable peripheral hyperkeratosis with central yellowish pus. The pinkish papillomatous lesions were covered with thick crusts. They gave off a foul smell. Abundant fungus elements were present in the crusts and keratotic layer. The trichophytin skin test was positive. Immunologic test results revealed that the patient had hypergammaglobulinemia with hypoalbuminemia. However, she had no edema or immunologic abnormalities. The skin lesions were successfully treated with topical miconazole cream, oral griseofulvin, and topical sulconazole cream. The etiologic agent was identified as Microsporum ferrugineum Ota 1922. It seemed to us that the unusual skin manifestation were induced by her immunological response to fungal and bacterial infection due to a long history of Candida granuloma.     

Lipopolysaccharide suppresses albumin expression by activating NF-kappaB in rat hepatocytes

BACKGROUND: The severity of hypoalbuminemia has been shown to be related to morbidity and mortality in critical illness, illustrating the need for better understanding of the molecular mechanism of hypoalbuminemia. Lipopolysaccharide(LPS) is a key mediator which induces hypoalbuminemia in sepsis and septic shock. The present studies were performed to identify whether the reduction of albumin expression induced by LPS was mediated by activating nuclear factor kappa B(NF-kappaB) in cultured rat hepatocytes. MATERIALS AND METHODS: Primary rat hepatocytes were divided into five groups treated with normal saline or 1 ng/ml, 0.01 microg/ml, 0.1 microg/ml, or 1 microg/ml of LPS for 24 h. The albumin level in the supernatant and NF-kappaB activity in hepatocytes were measured. Hepatocytes were pretreated for 30 min with SN50 (a highly selected inhibitor of NF-kappaB) at different concentrations (10, 30, and 50 microg/ml). After 24 h of treatment with 1 microg/ml of LPS, the culture medium was measured for albumin level. Meanwhile, NF-kappaB activity in hepatocytes was assayed. RESULTS: LPS dramatically decreased albumin expression and enhanced NF-kappaB activity in rat hepatocytes, especially in the 1 microg/ml LPS group. This reduction in albumin expression induced by LPS can be completely inhibited by SN50 in different concentrations, and the maximal increase in albumin was observed at a SN50 dosage of 30 microg/ml. CONCLUSIONS: The results suggest that LPS inhibits albumin expression by activating NF-kappaB signaling. NF-kappaB is a critical signaling pathway in LPS-induced hypoalbuminemia which it is worthwhile to understand in studying the molecular mechanism of hypoalbuminemia in sepsis and septic shock.     

伏立康唑不同途径给药序贯治疗肺结核并发肺曲霉病效果及其影响因素分析

目的 探讨伏立康唑静脉滴注＋口服序贯给药治疗肺结核并发肺曲霉菌病的临床效果及安全性,并探讨疗效的影响因素。方法 根据治疗方式不同将2019年1月-2022年3月昆明市第三人民医院收治的162例肺结核并发肺曲霉菌病患者分为对照组和试验组,每组各81例。两组均对咳血、发热等临床症状进行对症药物治疗,同时采用常规抗肺结核药物治疗。对照组常规治疗基础上,采用注射用伏立康唑静脉滴注治疗,每天2次,首次剂量6 mg·kg^-1,之后每次4 mg·kg^-1,连续治疗6周;试验组前2周用药方案与对照组相同,2周后改为伏立康唑分散片口服治疗,每次0.2 g,每天2次,继续服药至6周。比较两组疗效、康复进程及安全性,并采用单因素及Logistic多因素方法分析疗效的影响因素。结果 试验组总有效率75.31%与对照组80.25%比较,差异无统计学意义（P＞0.05）;试验组咳嗽咳痰缓解时间、痰培养真菌转阴时间、肺部啰音消失时间、体温恢复时间与对照组比较,均无统计学意义（P＞0.05）;试验组不良反应总发生率为2.47%,显著低于对照组的11.11%（P＜0.05）。Logistic回归分析表明,肺部空洞、低蛋白血症、粒细胞缺乏是肺结核并发肺曲霉菌病疗效的独立危险因素（P＜0.05）。结论 伏立康唑静脉滴注+口服序贯治疗疗效与其静脉滴注治疗效果相当,且显著降低不良反应发生风险,疗效可靠,安全性高。肺部空洞、低蛋白血症、粒细胞缺乏是肺结核并发肺曲霉菌病疗效的独立危险因素。     

Plasma albumin and calcium concentrations,and long-term mortality in primary health care patients in Sweden

Objective Low plasma (p)-albumin and p-calcium concentrations are associated with increased mortality in hospitalised patients. There are few studies addressing this in primary care. Low p-calcium has been associated with mortality, but it is not known whether this applies to p-albumin. Could p-albumin and p-calcium be used as markers of an increased risk of mortality?Purpose To study p-albumin and p-calcium at baseline and their association with mortality after 10–14 years.Design Prospective cohort study using data from a large primary health care area and the National Swedish Cause of Death Register.Setting Primary health care in Skaraborg, Sweden.Subjects 43,052 patients (39.1% men), ≥18 years, 60.7 ± 18.4 years with p-albumin and p-calcium concentrations registered in 2001–2005.Main outcome measures P-albumin and p-calcium concentrations at baseline and their association with mortality after a mean follow-up period of 10.3 ± 4.0 years.Results Low p-albumin was associated with total mortality compared with normal p-albumin, greatest at lower ages (18–47 years). The hazard ratios for women and men were 3.12 (95% CI 1.27–7.70) and 4.09 (95% CI 1.50–11.14), respectively. The increased mortality was seen in both cardiovascular and malignant diseases in both women and men. In contrast, low p-calcium was not associated with increased mortality, 1.00 (95% CI 0.96–1.05). Elevated p-calcium was associated with increased mortality, 1.17 (95% CI 1.13–1.22).Conclusions Low p-albumin could be a marker of an increased risk of mortality, especially in patients of younger ages. This finding should prompt diagnostic measures in order to identify underlying causes.

KEY POINTS

• Low p-albumin and calcium concentrations have been associated with increased mortality in hospitalised patients, but this is unexplored in primary care patients.
• A low p-albumin concentration at baseline was a risk marker for mortality; highest in the younger age groups.
• Increased mortality in both cardiovascular and malignant diseases was seen in both men and women with low compared with normal p-albumin concentrations.
• Elevated but not low p-calcium concentrations were associated with increased mortality after 10–14 years of follow-up.

     

Clinical Course of Macular Edema in Two Cases of Interferon-Associated Retinopathy Observed by Optical Coherence Tomography

Background Interferon (IFN)-associated retinopathy is typically characterized by retinal hemorrhages and cotton wool spots at the posterior fundus, but visual function is usually maintained. With the use of optical coherence tomography (OCT), two patients with IFN-associated retinopathy who had developed macular edema and reduced visual acuity during the clinical course of IFN therapy were observed.Cases A 37-year-old man with chronic hepatitis C and a 59-year-old man with chronic myeloid leukemia, both of whom had received IFN therapy, were referred to our outpatient clinic. The former patient had complained once that his visual acuity had decreased after the termination of IFN therapy, and the latter patient complained twice during IFN therapy that his visual acuity had decreased.Observations In both patients, at the time of the visual disturbances, macular edema was clearly observed by OCT. Hypoalbuminemia and thrombocytopenia were observed at this time also. After the remission of the hypoalbuminemia and thrombocytopenia, the macular edema observed by OCT disappeared and visual acuity returned to normal.Conclusion During and after IFN therapy, OCT is a useful examination technique for revealing macular edema in patients who have decreased vision. Ophthalmologists should be aware of the ocular side effects of IFN therapy and carefully monitor patients for the possible occurrence of hypoalbuminemia and thrombocytopenia. Jpn J Ophthalmol 2005;49:231–234 © Japanese Ophthalmological Society 2005