Choice of Approach Does Not Affect Clinical and Radiologic Outcomes: A Comparative Cohort of Patients Having Anterior Lumbar Interbody Fusion and Patients Having Lateral Lumbar Interbody Fusion at 24 Months.

STUDY DESIGN: Retrospective analysis of prospectively collected registry data. OBJECTIVE: This study aimed to compare the clinical and radiologic outcomes between comparative cohorts of patients having anterior lumbar interbody fusion (ALIF) and patients having lateral lumbar interbody fusion (LLIF). METHODS: Ninety consecutive patients were treated by a single surgeon with either ALIF (n = 50) or LLIF (n = 40). Inclusion criteria were patients age 45 to 70 years with degenerative disk disease or grade 1 to 2 spondylolisthesis and single-level pathology from L1 to S1. Patient-reported outcome measures included pain (visual analog scale), disability (Oswestry Disability Index [ODI]), and quality of life (Short Form 36 physical component score [PCS] and mental component scores [MCS]). Assessment of fusion and measurement of lordosis and posterior disk height were performed on computed tomography scans. RESULTS: At 24 months, patients having ALIF had significant improvements in back (64%) and leg (65%) pain and ODI (60%), PCS (44%), and MCS (26%; p < 0.05) scores. Patients having LLIF had significant improvements in back (56%) and leg (57%) pain and ODI (52%), PCS (48%), and MCS (12%; p < 0.05) scores. Fourteen complications occurred in the ALIF group, and in the LLIF group, there were 17 complications (p > 0.05). The fusion rate was 100% for ALIF and 95% for LLIF (p = 0.1948). ALIF added ∼6 degrees of lordosis and 3 mm of height, primarily measured at L5-S1, and LLIF added ∼3 degrees of lordosis and 2 mm of height between L1 to L5. Mean follow-up was 34.1 months. CONCLUSIONS: In comparative cohorts of patients having ALIF and patients having LLIF at 24 months postoperatively, there were no significant differences in clinical outcomes, complication rates, or fusion rates.

Anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2: a prospective study of complications.

OBJECT: The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) is controversial regarding the reported complication rates and cost. The authors aimed to assess the complication rates of performing ALIF using rhBMP-2. METHODS: This is a prospective study of consecutive patients who underwent ALIF performed by a single spine surgeon and a single vascular surgeon between 2009 and 2012. All patients underwent placement of a polyetheretherketone (PEEK) cage filled with rhBMP-2 and a separate anterior titanium plate. Preoperative clinical data, operative details, postoperative complications, and clinical and radiographic outcomes were recorded for all patients. Clinical outcome measures included back and leg pain visual analog scale scores, Oswestry Disability Index (ODI), and SF-36 Physical and Mental Component Summary (PCS and MCS) scores. Radiographic assessment of fusion was performed using high-definition CT scanning. Male patients were screened pre- and postoperatively regarding sexual dysfunction, specifically retrograde ejaculation (RE). RESULTS: The study comprised 131 patients with a mean age of 45.3 years. There were 67 men (51.1%) and 64 women (48.9%). Of the 131 patients, 117 (89.3%) underwent ALIF at L5-S1, 9 (6.9%) at L4-5, and 5 (3.8%) at both L4-5 and L5-S1. The overall complication rate was 19.1% (25 of 131), with 17 patients (13.0%) experiencing minor complications and 8 (6.1%) experiencing major complications. The mean estimated blood loss per ALIF level was 115 ml. There was 1 incidence (1.5%) of RE. No significant vascular injuries occurred. No prosthesis failure occurred with the PEEK cage and separate anterior screw-plate. Back and leg pain improved 57.2% and 61.8%, respectively. The ODI improved 54.3%, with PCS and MCS scores improving 41.7% and 21.3%, respectively. Solid interbody fusion was observed in 96.9% of patients at 12 months. CONCLUSIONS: Anterior lumbar interbody fusion with a vascular access surgeon and spine surgeon, using a separate cage and anterior screw-plate, provides a very robust and reliable construct with low complication rates, high fusion rates, and positive clinical outcomes, and it is cost-effective. The authors did not experience the high rates of RE reported by other authors using rhBMP-2.

Intercellular adhesion molecule-1 deficiency is protective against nephropathy in type 2 diabetic db/db mice.

Diabetic nephropathy is a leading cause of end-stage renal failure and is a growing concern given the increasing incidence of type 2 diabetes. Diabetic nephropathy is associated with progressive kidney macrophage accumulation and experimental studies suggest that intercellular adhesion molecule (ICAM)-1 facilitates kidney macrophage recruitment during type 1 diabetes. To ascertain the importance of ICAM-1 in promoting type 2 diabetic nephropathy, the development of renal injury in ICAM-1 intact and deficient db/db mice with equivalent hyperglycemia and obesity between ages 2 and 8 mo was examined and compared with results with normal db/+ mice. Increases in albuminuria (11-fold), glomerular leukocytes (10-fold), and interstitial leukocytes (three-fold) consisting of predominantly CD68+ macrophages were identified at 8 mo in diabetic db/db mice compared with nondiabetic db/+ mice. In comparison to db/db mice, ICAM-1-deficient db/db mice had marked reductions in albuminuria at 6 mo (77% downward arrow) and 8 mo (85% downward arrow). There was also a significant decrease in glomerular (63% downward arrow) and interstitial (83% downward arrow) leukocytes in ICAM-1-deficient db/db mice, which were associated with reduced glomerular hypertrophy and hypercellularity and tubular damage. The development of renal fibrosis (expression of TGF-beta1, collagen IV, and interstitial alpha-smooth muscle actin) was also strikingly attenuated in the ICAM-1-deficient db/db mice. Additional in vitro studies showed that macrophage activation by high glucose or advanced glycation end products could promote ICAM-1 expression on tubular cells and macrophage production of active TGF-beta1. Thus, ICAM-1 appears to be a critical promoter of nephropathy in mouse type 2 diabetes by facilitating kidney macrophage recruitment.

Macrophages in streptozotocin-induced diabetic nephropathy: potential role in renal fibrosis.

BACKGROUND: Renal fibrosis is central to the progression of diabetic nephropathy; however, the mechanisms responsible for fibroblast and matrix accumulation in this disease are only partially understood. Macrophages accumulate in diabetic kidneys, but it is unknown whether macrophages contribute to renal fibrosis. Therefore, we examined whether macrophage accumulation is associated with the progression of renal injury and fibrosis in type 1 diabetic nephropathy and whether macrophages exposed to the diabetic milieu could promote fibroblast proliferation. METHODS: Kidney macrophages, renal injury and fibrosis were analysed in diabetic C57BL/6J mice at 2, 8, 12 and 18 weeks after streptozotocin injection. Isolated rat bone marrow macrophages were stimulated with diabetic rat serum or carboxymethyllysine (CML)-bovine serum albumin (BSA) to determine whether macrophage-conditioned medium could promote the proliferation of rat renal (NRK-49F) fibroblasts. RESULTS: Progressive injury and fibrosis in diabetic nephropathy was associated with increased numbers of kidney macrophages. Macrophage accumulation in diabetic mice correlated with hyperglycaemia (blood glucose, HbA1c levels), renal injury (albuminuria, plasma creatinine), histological damage and renal fibrosis (myofibroblasts, collagen IV). Culture supernatant derived from bone marrow macrophages incubated with diabetic rat serum or CML-BSA induced proliferation of fibroblasts, which was inhibited by pre-treating fibroblasts with interleukin-1 (IL-1) receptor antagonist or the platelet-derived growth factor (PDGF) receptor kinase inhibitor, STI-571. CONCLUSION: Kidney macrophage accumulation is associated with the progression of renal injury and fibrosis in streptozotocin-induced mouse diabetic nephropathy. Elements of the diabetic milieu can stimulate macrophages to promote fibroblast proliferation via IL-1- and PDGF-dependent pathways which may enhance renal fibrosis.

Fatalities associated with the use of gamma-hydroxybutyrate and its analogues in Australasia.

OBJECTIVE: To identify deaths in Australasia associated with overdose of gamma-hydroxybutyrate (GHB) and its precursors (gamma-butyrolactone and 1,4-butanediol). DESIGN: A retrospective search of medical and scientific information sources, as well as popular newsprint, for the period January 2000-August 2003, with formal clinical, toxicological and forensic evaluation of retrieved data. MAIN OUTCOME MEASURE: Death associated with forensic data implicating GHB or its analogues. RESULTS: Ten confirmed GHB-associated deaths were identified, with eight considered to be directly attributable to GHB. Only two of these eight cases were positive for ethanol toxicology. CONCLUSIONS: Our study supports the existing evidence that GHB overdose is associated with fatalities, and that fatal overdoses occur in the context of isolated use.

Health-related quality of life in Australian adults with renal insufficiency: a population-based study.

BACKGROUND: Health-related quality of life is increasingly recognized as an important outcome in clinical research and patient care. Although there are a large number of reports of quality of life in the setting of end-stage renal disease, the impact of lesser degrees of renal impairment in the general population has not been described. METHODS: Data relating to quality of life measured by the Medical Outcomes Study 36-Item Short Form (SF-36) was available for 10,525 participants (93.6%) of the Australian Diabetes, Obesity and Lifestyle Study, a randomly selected representative sample of the Australian population aged 25 years or older. Results are examined by category of renal function (Cockcroft-Gault estimated glomerular filtration rate: normal, > or =60 mL/min/1.73 m2; renal insufficiency, <60 mL/min/1.73 m2). RESULTS: Significant impairment in health-related quality of life was seen with renal insufficiency for all SF-36 scales except Vitality and Mental Health. Adjusting for the substantial comorbidity associated with renal insufficiency, scores for Physical Functioning, Role-Physical, General Health, Vitality, and Role-Emotional were significantly lower. Examination of age-specific effects on health-related quality of life showed that mental health was particularly impaired in the younger age group, and Physical Functioning, in the older age group with renal insufficiency. Patterns of impairment were similar in men and women. CONCLUSION: Results from this study indicate that the current emphasis on clinical interventions aimed at preserving renal function are likely to improve the negative impact of kidney disease on health-related quality of life; however, prospective studies are needed to confirm these findings.

Cardiovascular risk in dialysis patients: a comparison of risk factors and cardioprotective therapy between 1996 and 2001.

Cardiovascular disease (CVD) is the major cause of mortality in dialysis patients. Aspirin, beta-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors reduce CVD mortality in the general population, as may angiotensin II receptor antagonists. The prevalence of cardiovascular risk factors and usage rates of cardioprotective agents in end-stage renal failure are unknown. A retrospective, cross-sectional study of dialysis patients was performed to compare: (i) prevalence of cardiovascular risk factors (age, hypertension, hyperlipidaemia, diabetes mellitus, and smoking); (ii) use of cardioprotective agents; and (iii) prevalence of cardiovascular disease between the time-points: 1996 (n = 262) versus 2001 (n = 369). We found an increase in the risk factors of age (53.6 +/- 14.9 years in 1996 vs 58.4 +/- 14.3 in 2001; P < 0.001) and hyperlipidaemia (45 vs 51.8%; P < 0.001) between the two time-points, with a reduction in the prevalence of smoking (14.5 vs 8.1%; P = 0.016). There was no difference in the prevalence of cardiovascular disease (37.4 vs 40.7%; P = 0.44). Cardioprotective agents were underutilized, with improvement in prescribing practice between 1996 and in 2001, especially in the usage of statins (21.4 vs 38.7% in 2001; P = 0.019). In conclusion, CVD is the primary cause of mortality in our dialysis patients. Although traditional cardiovascular risk factors affect the majority of the dialysis population, underutilization of cardioprotective agents is common. Proof of efficacy of these agents in this population of enormous risk is urgently required.

Historical controlled trial of OKT3 versus basiliximab induction therapy in simultaneous pancreas-renal transplantation.

Simultaneous pancreas-kidney (SPK) transplant recipients are at high immunological risk of rejection. Antibody induction is beneficial but lymphocyte-depleting therapy is associated with a high incidence of side-effects. We performed a historical controlled trial to compare OKT3 versus anti-CD25 antibody (basiliximab) induction therapy with regard to patient, kidney and pancreas survival, as well as to examine for any differences in acute rejection, graft function, and infective complications. Twenty-eight consecutive SPK transplants were performed at the Monash Medical Centre between December 1997 and November 2001. Anti CD3 monoclonal antibody (OKT3) was used prior to March 2000 (n = 12) and basiliximab was used after (n = 16), both in combination with cyclosporin, mycophenolate, and prednisolone. A retrospective comparison of outcomes was performed. At 6 months, patient (100 vs 100%), kidney (91.7 vs 91.7%) and pancreas (75 vs 83.3%) survival were similar in the OKT3 and basiliximab groups, respectively. A minority of subjects in each group remained free from rejection (42% basiliximab vs 25% on OKT3, P = NS). Renal function was superior in the basiliximab group (mean calculated creatinine clearance 79.4 +/- 11.9 vs 54.5 +/- 15.9 mL/min for basiliximab vs OKT3, P < 0.001). The incidence of major opportunistic infection was lower in basiliximab-treated patients (9 vs 50% in the OKT3 group, P = 0.033). Basiliximab was associated with similar 6-month patient, kidney and pancreas survival, superior renal function and less opportunistic infection as compared with OKT3 induction therapy in SPK transplants. Basiliximab is at least as effective and is safer than OKT3 for induction therapy in SPK transplantation.