Prevalence of knee stiffness after arthroscopic bone suture fixation of tibial spine avulsion fractures in adults.

BACKGROUND: Tibial spine avulsion fractures (TSAFs) occur chiefly in adolescents. Few published data are available on outcomes after arthroscopic surgical treatment of TSAFs in adults. OBJECTIVES: To evaluate outcomes of consecutive patients with TSAFs managed by arthroscopic bone suture followed by a standardised non-aggressive rehabilitation programme. HYPOTHESIS: Arthroscopic bone suture followed by non-aggressive rehabilitation therapy reliably produces satisfactory outcomes in adults with TSAF. METHODS: Thirteen adults were included. Outcomes were evaluated based on the Tegner score, International Knee Documentation Committee (IKDC) score, anterior-posterior knee laxity, passive and active motion ranges, and radiological appearance. RESULTS: After a mean follow-up of 41±27months (12-94months), all 13 patients had healed fractures without secondary displacement. No patient had knee instability. Post-operative stiffness was noted in 5 patients (2 with complex regional pain syndrome and 3 with extension lag), 1 of whom required surgical release. The mean IKDC score was 91.3±11.7. The mean Tegner score was 5.46±1.37 compared to 6.38±0.70 before surgery. Mean tibial translation (measured using the Rolimeter) was 1.09±1.22mm, compared to 5.9±1.85mm before surgery. CONCLUSION: The outcomes reported here support the reliability of arthroscopic bone suture for TSAF fixation. Nevertheless, a substantial proportion of patients experienced post-operative stiffness, whose contributory factors may include stunning of the quadriceps due to the short time from injury to surgery and the use of a gentle rehabilitation programme. LEVEL OF EVIDENCE: IV, retrospective study of treatment outcomes.

Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta-Analysis.

Despite their clinical efficacy, concerns about calcineurin inhibitor (CNI) toxicity make alternative regimens that reduce CNI exposure attractive for renal transplant recipients. In this systematic review and meta-analysis, we assessed four CNI immunosuppression strategies (minimization, conversion, withdrawal, and avoidance) designed to reduce CNI exposure and assessed the impact of each on patient and allograft survival, acute rejection and renal function. We evaluated 92 comparisons from 88 randomized controlled trials and found moderate- to high-strength evidence suggesting that minimization strategies result in better clinical outcomes compared with standard-dose regimens; moderate-strength evidence indicating that conversion to a mammalian target of rapamycin inhibitor or belatacept was associated with improved renal function but increased rejection risk; and moderate- to high-strength evidence suggesting planned CNI withdrawal could result in improved renal function despite an association with increased rejection risk. The evidence base for avoidance studies was insufficient to draw meaningful conclusions. The applicability of the review is limited by the large number of studies examining cyclosporine-based strategies and low-risk populations. Additional research is needed with tacrolimus-based regimens and higher risk populations. Moreover, research is necessary to clarify the effect of induction and adjunctive agents in alternative immunosuppression strategies and should include more comprehensive and consistent reporting of patient-centered outcomes.

Diaphyseal tibiofibular synostosis in professional athletes: Report of 2 cases.

Anterior leg pain is common in professional athletes and tibiofibular synostosis is reported to be a rare cause of anterior compartment pain or ankle pain related to sports activities. The management and appropriate treatment of this condition in professional athletes is controversial and the literature on the topic is sparse. Distal synostosis is usually related to ankle sprain and syndesmotic ligament injury, and proximal synostosis has been linked to leg length discrepancy and exostosis. Mid-shaft synostosis is even less common than proximal and distal forms. We present the treatment of mid-shaft tibiofibular synostosis in 2 cases of professional athletes (soccer and basketball player), along with a review of the literature. When diaphyseal synostosis is diagnosed, first-line conservative treatment, including ultrasound-guided steroid injection is recommended. However, if it does not respond to conservative management, surgical resection may be indicated to relieve symptoms.

High-density lipoproteins in the prevention of cardiovascular disease: changing the paradigm.

High-density-lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent inverse predictor of cardiovascular events. Although the causal nature of this association has been questioned, HDL and its major protein, apolipoprotein (apo)A1, have been shown to prevent and reverse atherosclerosis in animal models. In addition, HDL and apoA1 have several putatively atheroprotective functions, such as the ability to promote efflux of cholesterol from macrophages in the artery wall, inhibit vascular inflammation, and enhance endothelial function. Therefore, HDL-C and apoA1 have been investigated as therapeutic targets for coronary heart disease. However, recent clinical trials with drugs that raise HDL-C, such as niacin and inhibitors of cholesteryl ester transfer protein, have been disappointing. Here, we review the current state of the science regarding HDL as a therapeutic target.

Late acute kidney transplant rejection: clinicopathological correlates and response to corticosteroid therapy.

Acute rejection is a major cause of kidney allograft dysfunction. It is important to distinguish between cellular and antibody-mediated rejection to guide the treatment strategy. The management of acute antibody-mediated rejection includes aggressive therapy with plasmapheresis and intravenous immunoglobulin. C4d staining of peritubular capillaries has emerged as a valuable tool in identifying antibody-mediated rejection. Late acute rejection has a worse prognosis than early acute rejection. The clinical and pathological features of late acute kidney allograft rejection are not fully understood. We studied the clinicopathological correlates of late acute rejection in our patient population. During an 8-year period, all patients who had late acute rejection (6 months posttransplant) were identified. Patients with severe chronic changes and transplant glomerulopathy were excluded. Patients were divided into C4d+ and C4d- groups [corrected]. Histopathological features and treatment response were evaluated. Nine patients met inclusion criteria (4 C4d+, 5 C4d-). Maintenance therapy consisted of mycophenolate mofetil, calcineurin inhibitors, and low-dose prednisone. All patients received intravenous methlyprednisolone or high-dose oral prednisone as antirejection therapy. Seventy-five percent of patients in the C4d+ group and 80% of patients in the C4d- group had a clinical response to antirejection therapy. The majority of C4d+ patients with late acute rejection who were treated with corticosteroids alone responded to treatment. The study raises the possibility that a subset of C4d+ patients with acute rejection who do not have severe chronic changes might respond to corticosteroid therapy alone.

Unrecognized acute phosphate nephropathy in a kidney donor with consequent poor allograft outcome.

Acute phosphate nephropathy following a large phosphate load is a potentially irreversible cause of kidney failure. Here, we report on the unfavorable graft outcome in two recipients of deceased donor kidneys from a donor who had evolving acute phosphate nephropathy at the time of organ procurement. The donor, a 30-year-old with cerebral infarction, developed hypophosphatemia associated with diabetic ketoacidosis and was treated with intravenous phosphate resulting in a rise in serum phosphorus from 0.9 to 6.1 mg/dL. Renal biopsies performed on both recipients for suboptimal kidney function revealed acute tubular injury and diffuse calcium phosphate microcrystal deposits in the tubules, which were persistent in subsequent biopsies. A retrospective review of preimplantation biopsies performed on both kidneys revealed similar findings. Even though initial renal histology in both recipients was negative for BK virus, they eventually developed BK viremia with nephropathy but both had a substantive virologic response with therapy. The first patient returned to dialysis at 6 months, while the other has an estimated glomerular filtration rate of 12 mL/min, 17 months following his transplant. We conclude that unrecognized acute phosphate nephropathy in a deceased donor contributed substantially to poor graft outcome in the two recipients.

The Miami experience with almost 100 multivisceral transplants.

We report our experience with 98 patients who received primary multivisceral transplantations. Three eras can be distinguished based on the evolution of technique, immunosuppression, and monitoring: August 1994 to December 1997 (first era); January 1998 to December 2000 (second era); and January 2001 to present (third era). Sixteen patients were transplanted during the first era, 18 during the second era, and 64 during the third era. Fifty-three patients are alive with a median follow-up of 37.5 months (range: 1 to 116 months). The leading cause of mortality was infection (n = 17), followed by rejection (n = 6). Seven patients required retransplantation and five of them subsequently died. The estimated 3-year survival was 25% +/- 11% for era 1; 44% +/- 12% for era 2; and 58% +/- 7% for era 3. Additionally, 45.3% (29/64) of patients in the third era never developed rejection versus 23.5% (8/34) of patients in the first two eras combined. The percentage of patients who developed a moderate or severe rejection was significantly less in the third era compared with the first two eras combined, 31.6% (20/64) versus 67.6% (23/34). A comparison of the hazard rate of developing severe rejection showed a protective effect of the multivisceral graft (P = .0001). In conclusion, multivisceral transplantation is indicated for patients with short bowel syndrome and extended abdominal catastrophies. Evolution in surgical techniques, immunosuppression, and monitoring have improved patient survival, which is now similar to that of other complex solid organ transplants.

International grading scheme for acute rejection in small bowel transplantation: implementation and experience at the University of Miami.

In 2003, an international collection of pathologists and clinicians proposed a unified grading system for acute cellular rejection in endoscopically derived small intestine allograft biopsies. This grading system was implemented at the University of Miami over the past 2 years and the results are presented herein. A total of 1136 small bowel allograft biopsies with sufficient tissue for analysis were obtained from 123 hospitalized, clinic, and referral patients. The overall most common diagnosis assessing all time periods was grade IND (40%), and grade 1 rejection or greater was present in 19% percent of biopsies. A suspected vascular component to the acute rejection as identified by specific mucosal vascular changes was present in 6% of cases. Clinical decision making was very consistent with different grades. Our experience has confirmed that this new grading system is reliable and identifies clinical subsets of patients that can receive different therapy. We recommend that this international grading system be implemented for acute cellular rejection in bowel allografts as a means to standardize pathological assessment of alloimmune-induced graft injury, which will allow comparisons between different centers and clinical trials.

Analysis of rejection episodes in over 100 pediatric intestinal transplant recipients.

Rejection after intestinal transplant is a significant source of morbidity and mortality. We analyzed number of rejections, severity, and duration of episodes in pediatric recipients of intestinal transplants. One hundred eighteen intestinal transplants were performed: intestine (n = 27), liver-intestine (n = 27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186 rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27). Duration of episodes doubled for each increasing step in severity. Treatment of mild rejection was with steroids, moderate rejection was treated with OKT3, severe rejection required OKT3 and organ removal. Most rejections occurred during the first month posttransplant, with the incidence of all rejections declining after 6 months posttransplant. Intestine and liver-intestine recipients had significantly higher probability of developing severe rejections, as compared to MVT. In summary, recipients of MVT seemed to be protected from rejection as compared to intestine or liver-intestine recipients.

CD55 and CD59 deficiency in transplant patient populations: possible association with paroxysmal nocturnal hemoglobinuria-like symptoms in Campath-treated patients.

Campath-1H therapy is directed to CD52, a small mw protein that has a glycosylphosphatidylinositol (GPI) anchor, which has a conventional structure similar to other GPI anchors such as CD55 and CD59. Paroxysmal nocturnal hemoglobinuria (PNH) results when cells have a somatic defect in the synthesis of GPI anchors and lack CD55 and CD59, as well as CD52. Several patients treated with Campath developed PNH-like symptoms with hemolysis and thrombosis. These patients were followed after therapy by measurement of peripheral CD55 and CD59 levels and showed an increased number of cells deficient in the expression of these molecules. Thereafter we instituted a screening program for the presence of CD55/59 levels in all pretransplant patients. Our results show that 17.3% of all pretransplant samples contained abnormal (9.7% of samples) or slightly abnormal (7.6% of samples) levels of granulocytes deficient in CD55 or CD59. This high prevalence of CD55/59 deficiency in Campath-treated patients with PNH-like symptoms suggests that a lack of these molecules (including CD52) could predispose to a complication of this immunosuppressive therapy.

The effect of gut metabolism on tacrolimus bioavailability in renal transplant recipients.

BACKGROUND: Tacrolimus, a substrate of CYP3A, has low and variable bioavailability similar to cyclosporine. Co-administration of ketoconazole, potent inhibitor of gut and hepatic CYP3A, has been shown to increase tacrolimus bioavailability in healthy volunteers. The purpose of this study is to assess the role of gut metabolism in the overall bioavailability of tacrolimus in a renal transplant population. METHODS: We prospectively studied 19 adult renal transplant recipients who were receiving tacrolimus as part of a quadruple, sequential immunosuppression regimen. Each patient received tacrolimus (4-hr intravenous dose of 0.04 mg/kg between postoperative days 2 and 4). Whole blood samples were collected over 24 hr. After a 24-hr washout period, a single oral dose of ketoconazole (400 mg) was administered followed by the same intravenous dose of tacrolimus, and subsequent samples were obtained. Steady state oral pharmacokinetic profiles were obtained between 1 and 3 months after transplant while patients were receiving twice daily dosing of tacrolimus to maintain whole blood levels between 10 and 20 ng/ml. Two days later, 400 mg of ketoconazole was administered orally 2 hr before to the morning dose. Whole blood samples were collected over 12 hr. RESULTS: In the absence of ketoconazole, 8.0% of the tacrolimus dose underwent first pass metabolism (E(H)), whereas in the presence of ketoconazole, first pass metabolism was 6.2% (P=0.01). Based on this difference in first pass metabolism, an increase of 2% in bioavailability is expected, but an increase of 47% is observed (P=0.001). CONCLUSIONS: This indicates that the gut metabolism of tacrolimus is extensive and contributes significantly to its bioavailability.

HSP27 in signal transduction and association with contractile proteins in smooth muscle cells.

Sustained smooth muscle contraction is mediated by protein kinase C (PKC) through a signal transduction cascade leading to contraction. Heat-shock protein 27 (HSP27) appears to be the link between these two major events, i.e., signal transduction and sustained smooth muscle contraction. We have investigated the involvement of HSP27 in signal transduction and HSP27 association with contractile proteins (e.g., actin, myosin, tropomyosin, and caldesmon) resulting in sustained smooth muscle contraction. We have carried out confocal microscopy to investigate the cellular reorganization and colocalization of proteins and immunoprecipitation of HSP27 with actin, myosin, tropomyosin, and caldesmon as detected by sequential immunoblotting. Our results indicate that 1) translocation of Raf-1 to the membrane when stimulated with ceramide is inhibited by vasoactive intestinal peptide (VIP), a relaxant neuropeptide; 2) PKC-alpha and mitogen-activated protein kinase translocate and colocalize on the membrane in response to ceramide, and PKC-alpha translocation is inhibited by VIP; 3) HSP27 colocalizes with actin when contraction occurs; and 4) HSP27 immunoprecipitates with actin and with the contractile proteins myosin, tropomyosin, and caldesmon. We propose a model in which HSP27 is involved in sustained smooth muscle contraction and modulates the interaction of actin, myosin, tropomyosin, and caldesmon.

Indomethacin in the management of elevated intracranial pressure: a review.

Elevated intracranial pressure occurs frequently in patients with severe head injury. A number of studies in recent years suggest that indomethacin may be useful in the management of elevated intracranial pressure. Indomethacin acts primarily by reducing cerebral blood flow and decreasing cerebral edema following head injury. This review summarizes the basic and clinical studies of the effects of indomethacin on cerebral blood flow, brain edema, and intracranial pressure. The pharmacology of indomethacin, and issues for future investigation in the use of indomethacin in severe head injury, are discussed.

Mummified insect as foreign body in the respiratory tract.

A case report of a child with a cockroach in bronchus is described.