Age affects outcomes in chronic kidney disease

Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m(2) for 18 to 44 year old patients to 15 ml/min per 1.73 m(2) for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels <45 ml/min per 1.73 m(2) at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of >3 ml/min per 1.73 m(2). In conclusion, age is a major effect modifier among patients with an eGFR of <60 ml/min per 1.73 m(2), challenging us to move beyond a uniform stage-based approach to managing CKD.     

Safety and Efficacy of Surgical Management of Hyperthyroidism: 15-year Experience from a Tertiary Care Center in a Developing Country

Background Ideal management of toxic goiter still remains elusive. Though surgical management of toxic multinodular goiter (MNG) is well accepted, surgical treatment of Graves’ disease (GD) is still controversial in view of the presumed increased incidence of complications. In this paper, we discuss the experience of the surgical management of hyperthyroidism at a specialized tertiary care endocrine center in a developing country, highlighting the minimal morbidity and satisfactory outcome in experienced hands. Materials and methods We retrospectively reviewed 325 consecutive patients with hyperthyroidism managed surgically from 1990 to 2005. The etiologic diagnoses were Graves’ disease (185), toxic MNG (105), and autonomously functioning thyroid nodules (AFTN) (n = 35). The indications for surgery in Graves’ patients were large goiter, relapse after antithyroid drug therapy (ATD), Graves’ ophthalmopathy, and presence of nodule. The indications for surgery in toxic MNG were retrosternal extension (n = 15), compressive symptoms (n = 20), and large size (grade II). Among the AFTN nodule size, those greater than 4 cm (85%) formed the major indication for surgery. Subjects with GD and toxic MNG were subjected to subtotal thyroidectomy (n = 93 prior to 1995) or total thyroidectomy (n = 205 post-1995). Hemithyroidectomy was the procedure of choice in patients with AFTN. Results Patients with Graves’ disease were younger in age, with shorter mean duration of goiter when compared with the other 2 groups. Eight percent of patients with Graves’ disease without a clinically palpable nodule and 25% of those with nodules had associated differentiated carcinoma, including papillary, follicular, and medullary thyroid cancer. Four percent of patients with toxic MNG had malignancy. Complications included temporary hypocalcemia (24%), permanent hypocalcemia (3%), and permanent vocal-cord palsy (1%). Conclusions Surgery for hyperthyroidism has negligible mortality and acceptable morbidity in experienced hands. It is a definite option in selected cases. Immediate and permanent cure of hyperthyroidism is achieved, with no recurrences, after total thyroidectomy. The cosmetic outcome is good, with excellent patient satisfaction and acceptance.     

The prostate needle biopsy gun: busting a myth

PURPOSE: It is widely reported that a prostate biopsy gun needle advances 0.5 cm and then obtains the subsequent 1.5 cm of tissue. Based on this presumed skip area it is recommended that the needle tip must be placed 0.5 cm from the capsule before firing to obtain the capsule with the specimen. Contrary to this longstanding recommendation, in our experience we have observed that there is no such skip area. We determined the actual content of a needle core by obtaining biopsies from an apple model with clinical correlation to validate our findings. MATERIAL AND METHODS: Using 3 types of spring-loaded biopsy needles we obtained 24 cores from an apple. We placed the biopsy needle tip directly adjacent to the capsule before firing the biopsy gun. Visual inspection of each biopsy core was done to confirm the presence or absence of the capsule (red apple peel). RESULTS: All cores had confirmed presence of the apple peel, confirming the absence of a skip area in the first 0.5 cm. CONCLUSIONS: Using spring-loaded biopsy guns we observed in an apple model that the capsule is obtained when the biopsy needle tip is placed directly adjacent to the capsule. Urologists placing the biopsy needle tip directly on the capsule in line with the projected trajectory will obtain the prostatic capsule in the specimen and should not withdraw the needle unless the gland depth is short enough so that there is risk of firing past the gland.     

Adrenomedullin and adrenomedullin-binding protein-1 downregulate inflammatory cytokines and attenuate tissue injury after gut ischemia-reperfusion

BACKGROUND: Recent studies have shown that adrenomedullin (AM) and AM-binding protein-1 (AMBP-1) possess anti-inflammatory properties in sepsis. We hypothesized that administration of AM/AMBP-1 after gut ischemia-reperfusion (I/R) downregulates inflammatory cytokines and attenuates tissue injury. METHODS: Male Sprague-Dawley rats (275-325 g) were used. Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery (SMA) for 90 minutes. Upon release of the SMA clamp, the animals were treated by AM (12 microg per kilogram of body weight) and AMBP-1 (40 microg per kilogram of body weight) in combination, or vehicle (1 mL 0.9% NaCl) over 30 minutes via a femoral vein catheter. The animals undergoing sham operation or ischemia for 90 minutes only, did not receive AM/AMBP-1 treatment. At 60 minutes after the completion of the treatment (ie, 90 minutes after reperfusion), blood samples were collected. Plasma AM and AMBP-1 were measured by radioimmunoassay and Western blot analysis, respectively. Serum levels of TNF-alpha, interleukin (IL)-1beta, IL-6, IL-10, transaminases (ie, alanine aminotransaminase, aspartate aminotransaminase), lactate, and creatinine were determined with the use of enzyme-linked immunosorbent assay and other standard methods. In additional groups of animals, the 10-day survival rate was recorded after gut I/R. RESULTS: Ischemia alone was sufficient to downregulate both AM and AMBP-1. Unlike AMBP-1 that remained decreased, AM levels increased significantly after reperfusion. I/R but not ischemia alone significantly increased serum levels of inflammatory cytokines. Moreover, I/R-induced tissue injury was evidenced by increased levels of transaminases, lactate, and creatinine. Administration of AM/AMBP-1 after ischemia, however, markedly reduced cytokine levels, attenuated tissue injury, and improved survival. CONCLUSIONS: AM/AMBP-1 may be a novel treatment to attenuate the reperfusion injury after gut ischemia.     

Anti-LFA-1 improves pig islet xenograft function in diabetic mice when long-term acceptance is induced by CTLA4Ig/anti-CD40L

BACKGROUND: It has been previously demonstrated that addition of anti-LFA-1 to a combination of CTLA4Ig and anti-CD40L induces the permanent acceptance of dopaminergic fetal pig xenografts when transplanted into the brain of wild-type mice. The purpose of this study was to test whether this costimulation blockade also can induce acceptance of adult pig islets transplanted to C57BL/6 mice with streptozotocin-induced diabetes. METHODS: Recipients were treated with CTLA4Ig/anti-CD40L+/-anti-LFA-1 or isotype control antibodies during the first week after transplantation. Half of the costimulation blockade-treated recipients had their grafts removed after 8 weeks. The other half was observed up to 5 months. RESULTS: Recipients treated with CTLA4Ig/anti-CD40L/anti-LFA-1 had significantly lower blood glucose and gained more weight than CTLA4Ig/anti-CD40L-treated recipients. CTLA4Ig/anti-CD40L-treated recipients exhibited unstable blood glucose. IPGTT of these recipients revealed a slow recovery to normal blood glucose levels at week 4. In comparison, CTLA4Ig/anti-CD40L/anti-LFA-1 treated recipients exhibited a significantly superior glucose clearance. CTLA4Ig/anti-CD40L+/-anti-LFA-1 treated recipients did not produce anti-pig IgG, whereas control antibody-treated mice did. CD4+ T cells from costimulation blockade-treated recipients proliferated less than CD4+ T cells from control antibody-treated mice when co-cultured with syngeneic antigen presenting cells loaded with pig islet antigens. CONCLUSIONS: CTLA4Ig/anti-CD40L/anti-LFA-1-treated recipients had superior islet function compared with CTLA4Ig/anti-CD40L-treated recipients. However, both costimulation blockade regimens led to islet graft acceptance up to 5 months after a 1-week treatment.     

Metastatic Differentiated Thyroid Carcinoma: ClinicopathologicalProfile and Outcome in an Iodine Deficient Area

Reports on metastatic differentiated carcinoma in endemic goiter regions are scarce. The aim of this study was to look into the clinicopathological profile and outcome of patients with metastatic differentiated thyroid carcinoma (DTC) of endemic origin. This was a retrospective study of 28 cases of metastatic DTC out of a total of 140 DTC patients managed between 1990 and June 1999. Demographic data, clinicopathological profile, operative and radioiodine ablation therapy details, and follow-up findings were noted. The overall incidence of distant metastases in our series was 20%. Mean age was 48.5 +/- 12.8 years (32.1%patients were < 45 years). Most metastases were detected synchronously (85.7%) and were multiple, with the skeletal system being the commonly affected site. Out of 22 cases having skeletal metastases, 6 patients were young (< 45 years). Though most patients with skeletal metastases had follicular carcinoma (FTC), 4 cases had papillary thyroid cancer (PTC). Near total or total thyroidectomy was done in 26 cases. Sixteen patients required regional lymph node dissection. Resection of metastases was performed in 9 cases.Histopathological diagnosis was PTC, FTC, and poorly differentiated carcinoma in 32.1%, 50.0%, and 17.9% of cases, respectively. Most patients had good symptomatic palliation following administration of I131 therapy. In 17.9% of cases there were locoregional recurrences. There was an overall 28.6% mortality. Two patients expired in the perioperative period. Six others died in follow-up (all within 3-9 months). In contrast to iodine sufficient regions, the incidence of metastases was high; the majority of cases had synchronous, symptomatic skeletal metastases. Skeletal metastases were not infrequent even in cases of PTC and in young patients. One-third of the cases were young. Though survival was poor despite aggressive management, significant symptomatic palliation could be achieved in most cases.     

A Novel Non-Invasive Adjuvant Biomechanical Treatment for Patients with Altered Rehabilitation after Total Knee Arthroplasty: Results of a Pilot Investigation

Background

Many factors contribute to suboptimal results after total knee arthroplasty (TKA) but little is known regarding the value of postsurgical rehabilitation after TKA. We examined the effects of an enhanced closed kinematic chain exercises program (AposTherapy) on gait patterns and clinical outcomes among patients with a lack of progress in their postsurgical rehabilitation.

Methods

Twenty-two patients were prospectively followed during the study. Gait spatiotemporal parameters were measured at the initial evaluation, after 15 minutes of therapy, and after 3 months of therapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the short form (SF) 36 health survey were completed by patients before treatment and after 3 months of treatment.

Results

The WOMAC and SF-36 scores improved significantly after 3 months of treatment. Gait velocity, single limb support, and step length of the operated leg improved significantly even after a single 15 minutes treatment. Normal gait velocity was observed in 36% of patients after 3 months of treatment.

Conclusions

A physiotherapy program that included enhanced closed kinematic chain biomechanical therapy was beneficial for patients who experienced a suboptimal rehabilitation course after TKA.     

Risk factors for complications and readmission after operative fixation of pediatric femur fractures

Purpose

Operative fixation of pediatric femur fractures with intramedullary implants has grown in popularity in recent decades. However, risk factors for short-term adverse events and readmission have not been well studied.

Methods

Pediatric patients who underwent intramedullary nailing of a femur fracture between 2012 and 2013 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Risk factors for any adverse event (AAE) and readmission after intramedullary nailing were evaluated using univariate and multivariate analysis.

Results

A total of 522 pediatric patients who underwent intramedullary nailing of the femur during the study period were identified. The mean age of this patient cohort was 10.2 ± 3.8 years. Review of the cases revealed that 18 (3.4 %) patients had AAE and that 20 (3.8 %) patients were readmitted, of whom 13 (2.5 %) underwent a reoperation. Independent risk factors for AAE were a cardiac comorbidity [odds ratio (OR) 12.7, 95 % confidence interval (CI) 1.5, 103.7], open fracture (OR 10.2, 95 % CI 1.4, 74.4), and prolonged operative time (OR 17.5, 95 % CI 6.1, 50.5). Independent risk factors for readmission were a central nervous system disorder (OR 4.5, 95 % CI 1.3, 16.2) and a seizure disorder (OR 4.9, 95 % CI 1.0, 23.5).

Conclusions

The results of the multivariate analysis suggest that cardiac comorbidities, open fractures, and prolonged operative time increase the risk for AAE and that central nervous system disorders and seizure disorders may increase the risk for readmission. Surgeons should be aware of these risk factors and counsel the families of pediatric patients who undergo intramedullary nailing of femur fractures.