Measuring Kidney Disease–Related Loss in Samples of Predialysis and Dialysis Patients: Validating the Kidney Disease Loss Scale

Background and objectives: Kidney disease–related loss is clinically significant in patients with ESRD and is related to depression and quality of life. The Kidney Disease Loss Scale (KDLS) was recently developed for long-term dialysis patients as a means of studying loss and applying it to clinical practice; however, its validity and usability in the other developmental stages of ESRD—predialysis and early dialysis—remain unknown. This study examined the validity and reliability of the KDLS in the long-term dialysis, early dialysis, and predialysis populations.Design, setting, participants, & measurements: Four groups of participants were recruited from four large university teaching hospitals in the Sydney metropolitan area. Participants were long-term dialysis (n = 151), early dialysis (n = 163), and predialysis (n = 111) patients. An additional independent group of dialysis (n = 50) patients were recruited to measure the test–retest reliability. Multisample confirmatory factor analysis and correlational analysis were used.Results: Results demonstrated good internal consistency and test–retest reliability for KDLS. Multisample confirmatory factor analysis indicated that the factor structure of KDLS was invariant across samples and thus supported its construct validity. The convergent and discriminant validities of KDLS were supported by its correlations with scales that measure health-related quality of life, depression, and positive affect in the expected directions and magnitudes. The KDLS was sensitive to the developmental stages of ESRD.Conclusions: These findings demonstrated that the concept of loss exists in dialysis patients. The KDLS is a reliable measure of loss in ESRD and valid in the developmental stages of ESRD.Loss, conceptualized as cognitive and affective grief responses to individual losses characterized by rumination of and yearning for losses, disbelief, and stunned feelings, is clinically significant in chronic illnesses and ESRD (kidney disease that requires renal replacement therapy) (1–5). Loss has traditionally been studied in relation to death but has been extended to examine the losses that are associated with chronic illnesses and their psychological consequences (6,7). Facing multiple losses, patients with ESRD often experience negative grief responses that may continue for years and affect their mental health (2,5).Loss has special interest in ESRD because of its relationship with depression, which is highly prevalent in this population and associated with other patient outcomes, such as mortality, quality of life (QoL), and treatment adherence (8,9). Loss, a distinct construct from depression (2,5,10), is seen as either a cause or a consequence of depression (11,12). Moreover, it has been identified by both patients with ESRD and health staff as one of the important factors in psychosocial adaptation and QoL (4). Thus, studying loss is important in understanding its contribution to depression and QoL in patients with ESRD as well as providing new insights into potential interventions (2). Loss research has remained limited, partly because of the lack of a measure that is specific for kidney disease–related loss.Recently, with a long-term dialysis sample, the Kidney Disease Loss Scale (KDLS) was developed to measure the level cognitive and affective responses of patients with ESRD to kidney disease– and dialysis-related losses and to identify the most important types of losses (2). Using the KDLS, a recent study found that loss, as a distinct construct, contributes to long-term dialysis patients'' level of depression and indirectly affects their QoL (2).For the KDLS to be widely usable in ESRD, its validity and reliability need to be established in other samples patients with ESRD, especially in two of the four developmental stages of the ESRD life cycle: Patients who have recently commenced dialysis (early dialysis patients) and those who are yet to commence dialysis (predialysis patients) (13,14). Examining the KDLS in these ESRD developmental stages would establish the validity and utility of the KDLS in the ESRD life cycle, and such validation would facilitate further study on loss in ESRD. This study aimed to (1) examine the construct validity of the KDLS by testing the consistency of its factor structure in the three samples long-term dialysis patients, early dialysis patients, and predialysis patients; (2) test its convergent-discriminant validity; and (3) examine its internal consistency and temporal stability.     

Does Sustained Weight Loss Reverse the Metabolic Syndrome?

The prevalence of the metabolic syndrome (MetS) has increased rapidly in North America in recent years. Presently, the MetS is found in 34.3% of the population, and the prevalence is likely to continue to increase in parallel with the obesity epidemic. Losing weight and long-term maintenance of the weight loss are primary targets to beneficially reverse all of the components of the MetS. This paper reviews the clinical and experimental evidence for the reversal of the metabolic complications related to the MetS that follows a sustained weight loss.     

Beta-Cell Preservation…Is Weight Loss the Answer?

Obesity is associated with an increased risk of type 2 diabetes (T2D). Pancreatic beta-cell failure is an early event in the development of glucose dysregulation and diabetes. Interventions to halt beta-cell failure in T2D include diet modification, exercise, and use of pharmacologic agents. There is evidence that abdominal obesity may contribute to diabetes through insulin resistance and beta-cell impairment. Pivotal long-term studies into the prevention of T2D have shown the importance of weight loss beside diet, lifestyle, and medication. The Finnish Diabetes Prevention Program (DPP) showed that weight loss gradually reduces the risk of diabetes, and that even modest weight loss can significantly reduce the incidence of T2D. Similarly, in the US DPP, weight loss as part of intensive lifestyle modification was the major factor in reducing the incidence of T2D in high-risk subjects, being more effective than drug intervention. While understanding the relationship between obesity and diabetes is complex, we know that weight loss has positive effects on adipose tissue. It causes an increase in the beneficial fat cell hormone adiponectin, and a decrease in adipose tissue inflammation. Also, it is associated with reduced insulin resistance and a consequential reduction in glucolipotoxicity, which can improve beta-cell function. In summary, weight loss improves glycemic control and thereby mitigates diabetes symptoms and complications, possibly through the preservation of beta-cell function. Therefore, efforts to prevent diabetes and preserve beta-cell function in patients with T2D should more consequently emphasize and target weight loss.     

Inflammation-Induced Bone Loss: Can it Be Prevented?

Inflammatory synovitis induces profound bone loss and OCLs are the instrument of this destruction. TNF blockers have an established role in the prevention of inflammatory bone loss in RA; however, not all patients respond to anti-TNF therapy and side effects may prevent long-term treatment in others. The B-cell--depleting antibody rituximab and the T-cell costimulation blocker abatacept are emerging as major treatment options for patients who are resistant to anti-TNF [96,97]. Proof-of-concept studies demonstrate that targeting RANK-mediated osteoclastogenesis prevents inflammatory bone loss and clinical application has only just begun. The efficacy of RANKL inhibition has been witnessed in trials of Denosumab, and RANKL-neutralizing antibodies are likely to become the treatment of choice for blocking RANKL in RA [77,78]. A major limitation of RANKL antagonism is that it does not treat synovitis. Therefore, anti-RANKL therapy most likely will be used in the context of MTX therapy. There is uncertainty about the possible extraskeletal adverse effects of long-term effects of long-term RANKL blockade. In particular, anti-RANKL therapy could jeopardize dendritic cell function or survival. The demonstrable role of OCLs in inflammation-induced bone loss also invites a reconsideration of the new BPs for bone protection [98]. Studies of ZA in preclinical models indicate that bone protection is comparable to that afforded by OPG. One possible caveat is that intravenous BPs are linked to jaw osteonecrosis [99], although the incidence is confined mainly to intensive treatment in the oncology setting. Although pulsed PTH stimulated bone formation in arthritic models, it has yet to be proven clinically in the context of powerful OCL inhibition with TNF or RANKL antagonists. With strategies that normalize OCL numbers, clinicians are poised to accomplish effective prevention of inflammation-induced bone loss.     

Zinc-α2-Glycoprotein Expression in Adipose Tissue of Obese Postmenopausal Women before and after Weight Loss and Exercise + Weight Loss

Objective

Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX + WL) on ZAG expression.

Design and Methods

A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25–46 kg/m²) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX + WL (n = 17) and WL (n = 16). ZAG expression was determined by RT-PCR.

Results

Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r = − 0.50, P < 0.005), sagittal diameter (r = − 0.42, P < 0.05), and positively related to VO₂max (r = 0.37, P < 0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r = − 0.39 to − 0.50, all P < 0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX + WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX + WL and WL.

Conclusions

Abdominal ZAG expression may be important in central fat accumulation and fitness but only modestly increase (nonsignificantly) with weight reduction alone or with aerobic training in obese postmenopausal women.     

Medical Record Documentation of Patients’ Hearing Loss by Physicians

BACKGROUND  Anecdotal evidence suggests that hearing loss, even when sufficient to prevent full access to spoken communication, often is underreported by patients and not documented by physicians. No published studies have investigated this issue quantitatively. OBJECTIVE  To assess the documentation of hearing loss in comprehensive physician notes in cases where the patients are known to have substantial binaural loss. DESIGN  Electronic medical record (EMR) notes for 100 consecutive patients with substantial binaural hearing loss were reviewed retrospectively at a large academic medical center. All records reviewed were created within 2 years before the patient’s audiometry. Comprehensive physician notes containing the headings “History” and “Physical Exam” were examined for documentation of hearing loss and scored as: no mention of loss; finding of loss; or hearing reported as normal. PARTICIPANTS  Consecutive adult patients with substantial binaural hearing loss by audiometry who also had a comprehensive medical assessment in their electronic medical record created within 2 years before audiometry. RESULTS  Thirty-six percent of EMRs had no mention of hearing loss, 28% reported some loss, and 36% percent indicated that hearing was normal. CONCLUSIONS  Substantial hearing loss, sufficient to prevent effective communication in the medical setting, often is underdocumented in medical records.     

Loss of heterozygosity on hromosome 1 in sporadic colorectal carcinoma

AIM: Loss of heterozygosity (LOH) on tumor suppressorgenes is believed to play a key role in carcinogenesis ofcolorectal cancer.When it occurs at a tumor suppressorgene locus with abnormal allele,neoplastic transformationhappens.In this study,we analyzed the LOH at 21 loci onchromosome 1 in sporadic colorectal cancer to identifyadditional loci involved in colorectal tumorigenesis.METHODS: Twenty-one polymorphic micro-satellite DNAmarkers were analyzed with PCR both in 83 cases ofcolorectal cancer and in normal tissues.PCR products wereeletrophoresed on an ABI 377 DNA sequencer.Genescan3.1 and Genotype 2.1 software were used for LOH scanningand analysis.χ~2 test was used to compare LOH frequencywith clinicopathological data.P<0.05 was considered asstatistically significant.RESULTS: The average LOH frequency of chromosome 1,short arm and long arm was 19.83%,18.00% and 21.66%,respectively.The 2 highest LOH loci with a frequency of36.54% and 32.50% were identified on DIS468 (1p36.33-p36.31) and DIS413 (1q31.3),respectively.On DIS2726locus,LOH frequency of rectal cancer was 28.57% (6/21),which was higher than that of colon cancer (0.00%,0/33)(P=0.002),suggesting that the mechanism of carcinogenisiswas different in both groups.CONCLUSION: Putative tumor suppressor genes onchromosome 1 may relate to sporadic colorectal carcinomas.Tumor-suppressor-genes might locate on 1p36.33-36.31and/or 1q31.3.     

Loss of heterozygosity： An independent prognostic factor of colorectal cancer

AIM: Colorectal cancers result from the accumulation of several distinct genetic alterations. This study was to investigate the frequency and prognostic value of loss of heterozygosity (LOH) and microsatellite instability (MSI) at 14 genetic loci located near or within regions containing important genes implicated in colorectal tumorigenesis. METHODS: We studied colorectal cancers with corresponding normal mucosae in 207 patients (139 males and 68 females, mean age at the time of tumor resection 66.2±12.4 years, range 22-88 years). There were 37 right-sided colonic tumors, 85 left-sided colonic tumors and 85 rectal tumors. The distribution of tumor staging was stage Ⅰ in 25, stage Ⅱ in 73, stage Ⅲ in 68, and stage Ⅳ in 41. We analyzed the LOH and MSI of HPC1, hMSH2, hMLH1, APC, MET, P53, NH23-H1, DCC, BAT25, BAT26, D17S250, MYCL1 and D8S254 with fluorescent polymerase chain reaction and denatured gel electrophoresis. High-frequency LOH was determined to be greater than three, or more than 50% of the informative marker with LOH. High-frequency MSI (MSI-H) was determined as more than four markers with instability (>30%). Correlations of LOH and MSI with clinical outcomes and pathological features were analyzed and compared. RESULTS: The occurrence of MSI-H was 7.25%, located predominantly in the right colons (7/15) and had a higher frequency of poor differentiation (6/15) and mucin production (7/15). LOH in at least one genetic locus occurred in 78.7% of the tumors and was significantly associated with disease progression. Of the 166 potentially cured patients, 45 developed tumor recurrence within 36 mo of follow-up. Clinicopathological factors affecting 3-year disease-free survival (DFS) were TNM staging, grade of differentiation, preoperative CEA level, and high LOH status. Patients with high LOH tumors had a significantly lower DFS (50%) compared with patients with low LOH tumors (84%). Of the patients developing subsequent tumor recurrence, the number and percentage of LOH were 2.97 and 46.8% respectively, similar to the stage IV disease patients. TNM staging had the most significant impact on DFS, followed by high LOH status. CONCLUSION: Clinical manifestations of LOH and MSI are different in colorectal cancer patients. High-frequency LOH is associated with high metastatic potential of colorectal cancers.     

Loss of vision associated with angioid streaks in β-thalassemia intermedia

An acquired diffuse elastic tissue defect that resembles inherited pseudoxanthoma elasticum (PXE) has been noticed with a significant age-related frequency in hemoglobin disorders, especially β-thalassemia and has been held responsible for a number of complications observed in these cases, some of which are quite severe. We report here two patients with β-thalassemia intermedia, who presented with severe visual acuity impairment associated with angioid streaks, the typical ocular manifestation of PXE.     

Obese African-American Women’s Perspectives on Weight Loss and Bariatric Surgery

Background African-American (AA) women have higher rates of obesity and obesity-related diseases but are less likely than other women to undergo bariatric surgery or have success with conventional weight loss methods. Objective To explore obese AA women’s perceptions regarding barriers to weight loss and bariatric surgery. Design Focus groups to stimulate interactive dialogue about beliefs and attitudes concerning weight management. Participants and Approach We partnered with a community organization to recruit women who were AA, were ≥18 years old, and had a body mass index (BMI) of ≥30 kg/m². We audiotaped the 90-minute focus groups and used content analysis for generating and coding recurring themes. Results In our sample of 41 participants, the mean age was 48.8 years and mean BMI was 36.3. Most participants were unmarried, had some postsecondary education, and reported good or fair health. About 85% knew someone who had undergone bariatric surgery. Qualitative analysis of 6 focus group sessions revealed that the most common barriers to weight loss were lack of time and access to resources; issues regarding self-control and extrinsic control; and identification with a larger body size. Common barriers to bariatric surgery were fears and concerns about treatment effects and perceptions that surgery was too extreme or was a method of last resort. Conclusions Only through the elimination of barriers can AA women receive the care needed to eliminate excess weight and prevent obesity-related morbidity and mortality.     

How Much Weight Loss is Effective on Nonalcoholic Fatty Liver Disease?

Background

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide with no specific treatment. Weight loss is the most effective therapeutic strategy in its management; however, there is no consensus on its specifics. Thus, this study was conducted to evaluate the effects of weight loss on liver enzymes, markers of inflammation, oxidative stress and CK18-M30 (cytokeratin 18) as a biomarker of hepatocellular apoptosis.

Objectives

To study the effect of weight reduction diet as an exclusive treatment for NAFLD.

Patients and Methods

Forty four patients with NAFLD received a diet including a 500 to 1000 kcal per day intake reduction as30% fat, 15% protein, and 55% carbohydrate for six months. Anthropometric parameters, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lipid profile, malondialdehyde (MDA), TNF-α, IL-6, CK18-M30 were measured at baseline and at the end of the study. At the end of follow up, patients were classified as adherent or nonadherent to treatment according to a weight loss of ≥ 5%, or < 5% of initial body weight, respectively.

Results

Twenty five patients were classified as adherent group and nineteen as nonadherent group (9.7% vs. 1.9% total body weight loss after 6 months, respectively). After 6 months, changes in adherent and nonadherent groups were as follows: reduction in body weight from 93.7 ± 15.8 kg to 84.2 ± 13.4 kg vs. 94 ± 16.6 kg to 92.2 ± 16.2 kg (P < 0.05), BMI from 32.7 ± 3.9 to 29.5 ± 3.2 vs.31.8 ± 5.4 to 31.1 ± 5.3 (P < 0.001), and waist circumference from 105.1 ± 12.6 cm to 97.4 ± 9.8 cm vs.106.8 ± 14.2 cm to 103.7 ± 14 cm (P < 0.001), respectively. Diastolic blood pressure was significantly decreased in adherent group (from 80.2 ± 5.1 mmHg to 76.9 ± 5 mmHg; P < 0.001). Also, total cholesterol, LDL, triglyceride, ALT, AST, GGT and CK18-M30 levels were significantly decreased in the adherent group compared to nonadherent group (P < 0.05).

Conclusions

This intervention offers a practical approach for treatment of patients with NAFLD with diet therapy.     

Acute pancreatitis in aging animals: Loss of pancreatitis-associated protein protection?

AIM: To investigate the effect of age on severity of acute pancreatitis (AP) using biochemical markers, histology and expression of the protective pancreatitis-associated proteins (PAPs).METHODS: AP was induced via intraductal injection of 4% sodium taurocholate in young and old rats. Sera and pancreata were assayed at 24 h for the parameters listed above; we also employed a novel molecular technique to assess bacterial infiltration using polymerase chain reaction to measure bacterial genomic ribosomal RNA.RESULTS: At 24 h after induction of AP, the pancreata of older animals had less edema (mean ± SE histologic score of young vs old: 3.11 ± 0.16 vs 2.50 ± -0.11, P < 0.05), decreased local inflammatory response (histologic score of stromal infiltrate: 3.11 ± 0.27 vs 2.00 ± 0.17, P < 0.05) and increased bacterial infiltration (174% ± 52% increase from sham vs 377% ± 4%, P < 0.05). A decreased expression of PAP1 and PAP2 was demonstrated by Western blotting analysis and immunohistochemical staining. There were no differences in serum amylase and lipase activity, or tissue myeloperoxidase or monocyte chemotactic protein-1 levels. However, in the most-aged group, serum C-reactive protein levels were higher (young vs old: 0.249 ± 0.04 mg/dL vs 2.45 ± 0.68 mg/dL, P < 0.05).CONCLUSION: In older animals, there is depressed PAP expression related to a blunted inflammatory response in AP which is associated with worsened bacterial infiltration and higher C-reactive protein level; this may explain the more aggressive clinical course.     

Loss of heterozygosity and mRNA expression at DCC locus in gastric cancer

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Bariatric Surgery and Bone Loss: Do We Need to Be Concerned?

Despite significant improvement in weight and comorbid conditions, there is growing evidence that bariatric surgery may exert a negative effect on the skeleton. This review has focused on the impact of bariatric surgery on bone health, with the concern that bariatric surgery may increase skeletal fragility and fracture risk by accelerating bone loss. We have highlighted studies evaluating changes in bone metabolism after three commonly performed bariatric procedures including laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass surgery and increasingly popular sleeve gastrectomy. This review has also discussed some of the technical issues faced in measuring bone in obese populations and during dynamic weight loss. There is limited evidence regarding potential mechanisms for the reported observations of increased bone turnover and/or bone loss after bariatric surgery. We have reviewed the evidence surrounding potential factors affecting bone health in bariatric patients such as rapid weight loss per se, nutritional deficiencies, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones. Future prospective long-term cohort studies are needed to define how to quantify bone loss in individuals with obesity, particularly following massive weight loss, and for how long the bone changes continue. These studies will help clarify any negative clinical consequences of these changes, including future fracture risk in this unique group of patients.     

Weight Loss as a Cure for Type 2 Diabetes? Fact or Fantasy

Although individuals with obesity and type 2 diabetes are insulin resistant, pancreatic beta cell failure is the core defect that distinguishes individuals who eventually develop diabetes. This process is known to occur well before the onset of hyperglycemia. Although clinical trial data support the effectiveness of intensive lifestyle modification in delaying the onset of diabetes in obese subjects, less is known about the effects of and mechanisms underlying bariatric surgery, particularly gastric bypass surgery, on diabetes. The paper under evaluation clarifies the role of both lifestyle intervention and gastric bypass surgery on pancreatic beta cell function and raises questions regarding the role of weight loss versus incretin related mechanisms on recovery of beta cell failure.     

Effects of Orlistat- induced Weight Loss on Cardiovascular Risk Factors in Obese Chinese Subjects

Objectives To observe the influence of weight loss induced by orlistat on several cardiovascular diseases risk factors in obese Chinese subjects. Methods Sixty obese Chinese patients participated in a 24 week clinical trial. Participants were prescribed a slightly hypocaloric diet and exercise, then they were randomly assigned double -blind treatment with either orlistat 120 mg three times a day or placebo. Their body weight, blood pressure, fasting glucose, insulin, HbA1c, and serum lipid profile were performed before and after the weight loss intervention. Results After 24 weeks, orlistat -treated group lost more of their body weight than placebo group (6. 66 ± 0. 52 kg, 8. 44±4.08% and 1. 98 ± 0. 44 kg, 2. 44±1. 74 % , respectively, P < 0. 05) . Moreover, after treatment, orlistat - treated patients showed significant decreases in serum levels of total cholesterol, low density lipoprotein - cholesterol and high density lipoprotein - cholesterol ( P < 0.01), but in placebo group we found no change