Follow-up experience using histidine-tryptophan ketoglutarate solution in clinical pancreas transplantation

In May 2003, at Indiana University, the standard cold preservation solution University of Wisconsin (UW) solution was replaced by histidine-tryptophan ketogluatarate (HTK) solution. Earlier, we presented our initial experience with HTK in pancreas preservation with an analysis of the first 10 pancreas transplants. Here we report updated results with HTK in pancreas transplantation over the past 18 months. Between May 2003 and March 2005, a total of 87 pancreas transplants were performed with 78 of these organs utilizing HTK. Seventy five patients received 78 organ transplants. Surgical procedures performed were: simultaneous kidney pancreas transplantation (n = 50, 64%), pancreas after kidney transplantation (n = 19, 24%), solitary pancreas transplantation (n = 9, 12%). Donor and recipient data were collected with primary outcomes as primary nonfunction and 30-day graft and patient survivals, and compared to the UW cohort from our original report. Donor and recipient demographics were similar. Mean follow-up time is 12 +/- 6 months. The mean cold ischemia time was 9 +/- 3 hours. There were no cases of primary graft nonfunction. Thirty-day and 1-year patient survivals were 99% and 93%. The 30-day and 1-year graft survivals were 96% and 93%. There were five grafts lost, including three within the first month (two venous and one arterial thrombosis). There was one case of chronic rejection and one noncompliance. All other patients were insulin-independent by discharge. Serum fasting blood glucose and serial amylase remained comparable at all intervals posttransplantation. Within this range of cold ischemia time, HTK appears to provide effective pancreas preservation.     

Lymphangiogenesis does not occur in breast cancer

Breast cancer metastasis predominantly occurs via lymphatic vessels. However, the study of lymphatic vessels and lymphangiogenesis has been hampered by lack of specific markers. Recently, antibodies directed against M2A (D2-40), Podoplanin, and Prox-1 that specifically mark lymphatic vessels in paraffin-embedded sections have become available. These were used to study lymphangiogenesis in archival paraffin sections of normal breast (n = 23), fibrocystic disease (n = 7), ductal carcinoma in situ (n = 32), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 5). In addition, endothelial proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and proliferating cell nuclear antigen (PCNA). Expression of D2-40, Prox-1, and Podoplanin was seen in lymphatic vessels but not in blood vessels. Lymphatic vessels were seen in the peritumoral area and as "entrapped" intratumoral vessels adjacent to preexisting normal lobules and ducts. Unlike angiogenesis, there was no increase of lymphatic vessel density in association with neoplastic transformation. On the contrary, a marked reduction in intratumoral lymphatic vessel density was seen in comparison to normal breast tissue, fibrocystic disease, and ductal carcinoma in situ (P = 0.0001). There was an increase in peritumoral lymphatic vessel density as compared with normal breast (P = 0.0001). However, the endothelial cells in the "entrapped" or the peritumoral lymphatic vessels did not show any expression of PCNA indicating minimal or no proliferative activity. This was in contrast to the strong expression seen in adjacent tumor cells and blood vessel endothelial cells. Thus, lymphangiogenesis was not evident when studied by lymphatic vessel density or by lymph vessel endothelial proliferation.     

Intubating laryngeal mask for airway management in lateral decubitus state: comparative study of right and left lateral positions

Background. The intubating laryngeal mask has been used forthe emergency management of the airway in patients placed inthe lateral decubitus position. We have conducted this prospectivestudy to compare the feasibility of placement of an intubatinglaryngeal mask and blind tracheal intubation guided by the intubatinglaryngeal mask in patients placed in the right and the leftlateral positions. Methods. A total of 82 adults of both sexes with normal airways,scheduled for cholecystectomy, were allocated randomly to beplaced in either the right (n=41) or left (n=41) lateral positionfor the insertion of an intubating laryngeal mask and blindtracheal intubation guided by the intubating laryngeal maskunder balanced general anaesthesia. A sequence of standard manoeuvreswas performed after each failed attempt at intubating laryngealmask placement and intubation. Results. The intubating laryngeal mask was placed in all patientsat the first attempt. Ventilation of the lungs through the intubatinglaryngeal mask was possible in 40 patients (97.5%) from eachgroup after the first attempt at insertion (P=1). Followingadjustments, adequate ventilation could be achieved in all patients.The first attempt success rates of blind tracheal intubationwere 85.3% (35/41) and 87.8% (36/41) in the right and left lateralgroups, respectively (P=1). The remaining patients from bothgroups (except for one patient in the left lateral group whohad a failed intubation) were intubated at the second attempt. Conclusion. Insertion of the intubating laryngeal mask and blindtracheal intubation through it in the lateral position is feasiblein patients with normal airways. These procedures have a highand comparable success rate when patients are placed in theright and left lateral positions.     

Elastic stable intramedullary nailing for displaced proximal humeral fractures in older children

Purpose To demonstrate the effectiveness of intramedullary fixation of severely displaced proximal humeral physeal fractures in skeletally immature children using the elastic stable intramedullary nail (ESIN). Methods Retrospective recruitment of 14 patients aged 10–15-years old with severely displaced proximal humeral physeal fractures between 1999 and 2004 in a single regional specialist paediatric orthopaedic hospital. The fractures were graded using the Neer classification; severe displacement constituted Neer II–IV or displacement >1 cm and angulation >45°. Patients were followed up and assessed using the Disabilities of the Arm, Shoulder and Hand score (DASH) and the Neer Shoulder score. Radiographs were assessed for deformity. Subjective satisfaction was assessed. Results Fourteen patients with mean follow-up of 30 months (12–66 m) from surgery. All fractures were radiologically united at a median time of eight weeks (7–10 weeks). At follow-up, Neer Shoulder mean score was 96.79 (range 83–100) and DASH mean score 2.26 (0–7.5). Subjectively 71% were very satisfied and 29% were satisfied. Conclusions We commend stabilisation using ESIN in the management of the displaced proximal humeral physeal fracture in older children, once reduction of the fracture has been achieved by either closed or open means. ESIN is safe and allows early return to pre-injury function.     

Balloon kyphoplasty in the treatment of metastatic disease of the spine: a 2-year prospective evaluation

There is currently little data on the longer term efficacy and safety of balloon kyphoplasty (BKP) in patients with metastatic vertebral compression fractures (VCFs). To prospectively assess the long-term efficacy and safety of BKP in treating thoracic and lumbar spinal metastatic fractures that result in pain or instability. Sixty-five patients (37 men, mean age: 66 years) underwent 99 BKP procedures. Patient-related outcomes of pain visual analogue scale (VAS) and Oswestry Disability Index were assessed pre- and post-operatively and after 3, 6, 12 and 24 months. Correction of vertebral height and kyphotic deformity were assessed by radiographic measurements. Mean pain VAS and Oswestry Disability Index significantly improved from pre- to post-treatment (P < 0.0001), this improvement being sustained up to 24-month follow up. A gain in height restoration and a reduction of the post-operative kyphotic angle were seen post-operatively and at 3 months although these radiographic outcomes returned to pre-operative levels at 12 months. BKP was associated with a rate of cement leakage and incidence vertebral fracture of 12 and 8%, respectively. No symptomatic cement leaks or serious adverse events were seen during the 24 months of follow up. BKP is a minimally invasive procedure that provides immediate and long-term pain relief and improvement in functional ability in selected patients with metastatic VCFs. The procedure appears to have good long-term safety.     

Total hip arthroplasty following failed fixation of proximal hip fractures

Background:

Most proximal femoral fractures are successfully treated with internal fixation but a failed surgery can be very distressing for the patient due to pain and disability. For the treating surgeon it can be a challenge to perform salvage operations. The purpose of this study was to evaluate the short-term functional outcome and complications of total hip arthroplasty (THA) following failed fixation of proximal hip fracture.

Materials and Methods:

In a retrospective study, 21 hips in 20 patients (13 females and seven males) with complications of operated hip fractures as indicated by either established nonunion or fracture collapse with hardware failure were analysed. Mean age of the patients was 62 years (range 38 years to 85 years). Nine patients were treated for femoral neck fracture, 10 for intertrochanteric (I/T) fracture and two for subtrochanteric (S/T) fracture of the hip. Uncemented THA was done in 11 cases, cemented THA in eight hip joints and hybrid THA in two patients.

Results:

The average duration of follow-up was four years (2-13 years). The mean duration of surgery was 125 min and blood loss was 1300 ml. There were three dislocations postoperatively. Two were managed conservatively and one was operated. There was one superficial infection and one deep infection. Only one patient required a walker while four required walking stick for ambulation. The mean Harris Hip score increased from 32 preoperatively to 79 postoperatively at one year interval.

Conclusion:

Total hip arthroplasty is an effective salvage procedure after failed osteosynthesis of hip fractures. Most patients have good pain relief and functional improvements inspite of technical difficulties and high complication rates than primary arthroplasty.     

The challenge of discovering patient-level cardiovascular risk factors in chronic kidney disease

The goal of developing a CKD-specific cardiovascular risk score remains elusive and difficult. One approach to develop such a score is to evaluate conventional cardiovascular risk factors in an outcomes model. Nontraditional risk factors such as albuminuria can then be tested to evaluate the predictive value of these markers over and above traditional risk factors for patient-level decision making.     

Giant cell tumor of bone in children and adolescents

BACKGROUND: There are very few series that document giant cell tumor of bone (GCT) in the immature skeleton, and the reported incidence in literature varies from 1.8% to 10.6%. The purpose of this study was to document the incidence of GCT in patients with open physis in the Indian population and study the course of the disease with respect to its adult counterpart to see if it behaved any differently. METHODS: Between January 2000 and December 2005, 17 (6%) of 285 surgically treated patients with histologically proven GCT had open physis on imaging. Treatment was directed toward local control without sacrificing joint function, with most lesions treated with intralesional curettage. RESULTS: Fourteen (82%) patients were girls. The most common site was around the knee (53%). Of 15 lesions in tubular bones, 13 were epiphysiometaphyseal in location. An open physis did not prevent GCT from penetrating the epiphyseal cartilage. Histologically, the tumors were typical of GCT. Of 15 patients available for follow-up, 3 (20%) developed local recurrence. CONCLUSIONS: Although the overall incidence of GCT may be higher in the Asian population, the percentage of skeletally immature patients or those nearing skeletal maturity is similar to that described in literature. The biological behavior of the disease is similar to that seen in adults, except a marked female preponderance, principles of treatment, recurrence patterns, and course of the disease mirror the behavior of its adult counterpart.     

Hypertension is harmful to dialysis patients and should be controlled

Managing hypertension is among the commonest and most challenging features of end-stage renal disease and many clinical trials have shown the benefit of treating hypertension in the general population. If associations between blood pressure levels and cardiovascular outcomes in dialysis patients mirrored those seen in general population studies, one could argue that dialysis population-specific antihypertensive trials are unnecessary. Associations between blood pressure levels and outcomes are complex in this population. Naturally, comparisons of observational and experimental findings within intervention in patients with chronic kidney disease often show a surprising degree of disparity. In addition, the possibility of serious unmeasured co-morbid illnesses masking the true causal relationship between blood pressure and outcomes in this population looms large. Unfortunately, therefore, observational studies appear to be highly unreliable guides to identifying the truth regarding optimal management of hypertension. It appears, then, that controlled trials, alone, can inform appropriate treatment. Of late, intervention trials of antihypertensives in dialysis patients have begun to emerge. Though mostly small, less than definitive, and heterogeneous regarding patient selection, interventions and outcomes, several suggest net benefit and none suggests net harm. As dialysis patients are at vast cardiovascular risk, these findings suggest that aggressive treatment of hypertension should be the default approach, until large clinical trials show otherwise.     

Association of methylenetetrahydrofolate reductase genetic polymorphisms with atlantoaxial dislocation

OBJECT: Genetic mechanisms of atlantoaxial dislocation (AAD) have not previously been elucidated. The authors studied association of polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes enzymes of the folate pathway (implicated in causation of neural tube defects [NTDs]), in patients with AAD. METHODS: Molecular analysis of MTHFR polymorphisms (677C-->T, cytosine to thymine and, 1298A-->C, adenine to cytosine, substitutions) was carried out using polymerase chain reaction and restriction enzyme digestion in 75 consecutive patients with AAD and in their reducible (nine patients, 12%) and irreducible (66 patients, 88%) subgroups. Controls were 60 age- and sex-matched patients of the same ethnicity. Comparisons of genotype and allele frequencies were performed using a chi-square test (with significance at p < 0.05). RESULTS: The CT genotype frequency of MTHFR 677C-->T polymorphism was significantly increased in the full group of patients with AAD (odds ratio [OR] 3.00, 95% confidence interval [CI] 1.28-7.14, p = 0.005) as well as in the irreducible subgroup (OR 2.81, 95% CI 1.17-6.86, p = 0.01). The frequency of T alleles was also higher in the AAD group (25.3%) than in controls (15%). The comparison of the combined frequency of CT and TT genotypes with the frequency of the CC genotype again showed significant association in AAD (OR 2.63, 95% CI 1.98-5.90, p = 0.009) and the irreducible (OR 2.5, 95% CI 1.1-5.74, p = 0.016) subgroup. There was, however, no significant association of MTHFR 1298A-->C polymorphism with AAD. CONCLUSIONS: Both MTHFR 677C-->T polymorphism and higher T allele frequency have significant associations with AAD, especially the irreducible variety. Perhaps adequate supplementation of periconceptional folic acid to circumvent effects of this missense mutation (as is done for prevention of NTDs) would reduce the incidence of AAD.