The role of Platelet Rich Plasma and other orthobiologics in bone healing and fracture management: A systematic review.

BACKGROUND: Treatment of large bone defects and fracture healing complications (delayed and non-union) presents a substantial challenge for orthopaedic surgeons. Given that bone healing requires mechanical stability as well as a favourable biological microenvironment, orthobiologics such as Platelet-Rich Plasma (PRP) may have a significant clinical role to play. AIMS: To perform a systematic review of the available literature to assess the clinical effect of PRP, with or without other orthobiologics, on bone healing. METHOD: Two independent reviewers performed the literature search based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Clinical studies of any evidence, assessing effect of PRP with or without other orthobiologics on bone healing, were included. A qualitative analysis was carried out on the clinical and radiological outcomes reported. RESULT: 27 articles with 1631 patients (mean age = 43.56, 57.1% male, mean follow-up = 17.27 months) were included in the qualitative. Of the 27 studies, 13 dealt with fracture complications (delayed or non-unions), 7 with acute fracture healing, 4 with tibial osteotomies and lengthening procedures and 3 with lumbar spine pathology. 18/27 studies showed a clinical benefit of PRP, 8/27 showed no significant effect, and 1/27 showed a worse outcome with PRP. CONCLUSION: Our review suggests PRP may play a clinical role in bone healing but further randomised controlled trials (RCTs) using standardised outcomes should be performed to establish its efficacy.

Trafficking of ATP-sensitive potassium channels in health and disease.

K(ATP) channels (ATP-sensitive potassium channels), comprising four subunits each of Kir6.2 (inwardly rectifying potassium channel 6.2) and the SUR1 (sulfonylurea receptor 1), play a central role in glucose-stimulated insulin secretion by the pancreatic beta-cell. Changes in the number of channels at the cell surface are associated with genetic diseases of aberrant insulin secretion, including CHI (congenital hyperinsulinism) and NDM (neonatal diabetes mellitus). The present review summarizes advances in our understanding of the vesicular trafficking of normal K(ATP) channels and how genetic mutations in Kir6.2 interfere with such trafficking. A mutation, E282K, causing CHI, was found to disrupt a DXE [di-acidic ER (endoplasmic reticulum)-exit signal], thereby preventing its assembly into COPII (coatamer protein II)-coated vesicles and subsequent ER exit. The resultant decrease in the cell-surface density of the channel could explain the disease phenotype. Two mutations, Y330C and F333I, reported in patients with NDM, disrupted an endocytic traffic signal, thereby impairing CCV (clathrin-coated vesicle) formation and endocytosis. The consequent increase in the density of K(ATP) channels, together with an attenuated sensitivity to ATP reported previously, may account for the severe form of NDM.

A rare complication following laparoscopic TEP repair: case report and discussion of the literature.

Transabdominal pre-peritoneal and totally extra-preperitoneal (TEP) are common laparoscopic techniques used to repair inguinal hernias. With better equipment and techniques for creation of pneumoperitoneum serious complications are now infrequent. However, complications from these techniques that are beyond the control of the surgeon do occur. This report details a rare complication related to infection. It is the first such documented complication of TEP hernia repair. There follows a short literature review of rare complications of laparoscopic hernia repair. Surgeons should familiarize themselves with these potential pitfalls for a number of reasons including, counseling when obtaining consent and heightened awareness for infrequent complications during postoperative follow-up.

Age, gender, and autonomic tone effects on surface electrocardiographic indices of ventricular repolarization.

BACKGROUND: Prolonged QT offset dispersion (QToD), an index of heterogeneity of ventricular repolarization, is thought to be an independent predictor of all-cause and cardiovascular mortality. However the influence of gender and autonomic tone in healthy adults on age-related changes in measures of ventricular repolarization are not well characterized. METHODS: QToD and T wave complexity were measured in 56 healthy subjects with no detectable heart disease (by echo and stress test)-38 young subjects with a mean age of 28 +/- 4 years and 18 old subjects with a mean age of 71 +/- 7 years. QToD and T wave complexity were computed from 12-lead ECGs using the GE Marquette QT Guard automated analysis program with manual overreading at rest (baseline), following exercise, and double autonomic blockade with atropine and propranolol. Data was analyzed using factorial ANOVA. RESULTS: Young males had a significantly greater QToD than young and old females at baseline (28 +/- 5 ms, 23 +/- 5 ms, and 22 +/- 5 ms, respectively, P < 0.01), an intrinsic effect independent of changes in autonomic tone. In contrast, females had significantly greater T wave complexity than males following exercise and double autonomic blockade with a definite trend at baseline. There was no correlation between T wave complexity and QToD. CONCLUSIONS: Age and gender demonstrate a complex interaction on indices of myocardial repolarization with different measures behaving differently. These findings have implications for better understanding age and gender effects on myocardial electrophysiology.

Excitable gap in canine fibrillating ventricular myocardium: effect of subacute and chronic myocardial infarction.

INTRODUCTION: The existence of an excitable gap during ventricular fibrillation (VF) has been suggested in several prior studies. However, the effects of myocardial infarction on the presence and duration of an excitable gap during VF have not been evaluated. METHODS AND RESULTS: Electrophysiologic study was performed in normal dogs and in dogs with subacute and chronic infarction. Experimental infarction was produced by left anterior descending coronary ligation. The excitable gap was determined indirectly using either evaluation of intrinsic wavefronts during VF or from the shortest activation interval at individual sites using recordings from a 112-electrode plaque sutured to the epicardial surface of the left ventricle. The excitable gap also was correlated to local electrophysiologic and anatomic properties. The excitable gap using the wavefront propagation method and shortest activation method was significantly longer in subacute infarction dogs (48 +/- 17 msec and 37 +/- 18 msec, respectively) and chronic infarction dogs (41 +/- 14 msec and 35 +/- 14 msec, respectively) than normal dogs (32 +/- 13 msec and 30 +/- 11 msec, respectively; P < 0.05 normal vs subacute and chronic infarction dogs in both methods). The excitable gap occupied approximately 30% and 27% of the VF cycle length in all three groups using the wavefront propagation and shortest activation method, respectively. The excitable gap correlated better with local ventricular refractoriness determined using the wavefront propagation method than with the shortest activation method, but not at all with refractoriness determined using extrastimulus testing. Tissue necrosis was noted in subacute infarction dogs and fibrosis in chronic infarction dogs, but the gap was not highly correlated with anatomic changes. CONCLUSION: During VF, an excitable gap exists in both normal and infarcted canine ventricular myocardium. It is significantly longer in the presence of infarction. These finding have implications for understanding the pathophysiology of VF and targeting antiarrhythmic therapies.

Effects of sex and age on electrocardiographic and cardiac electrophysiological properties in adults.

Although differences in patient sex in heart rate and QT interval have been well characterized, sexual differences in other cardiac electrophysiological properties have not been well defined. The study population consisted of 354 consecutive patients without structural heart disease or preexcitation who underwent clinically indicated electrophysiological testing in the drug-free state. Atrial, AV nodal, and ventricular effective refractory periods (AERP, AVNERP, VERP) were determined at a pacing cycle length of 500 ms using an 8-beat drive train and 3-second intertrain pause. There were 124 men and 230 women with a mean age of 45 +/- 19 and 47 +/- 18 years, respectively. The sinus cycle length (SCL) was longer in men than in women (864 +/- 186 and 824 +/- 172 ms, respectively, P < 0.05). The QRS duration was significantly longer in men (90 +/- 12 ms) than women (86 +/- 13 ms) (P < 0.005). The HV interval was 48 +/- 9 ms in men and 45 +/- 8 ms in women (P < 0.05). The sinus node recovery time (SNRT) was significantly longer in men than in women (1215 +/- 297 ms and 1135 +/- 214 ms, respectively, P < 0.05). AERP and VERP were similar in both sexes. Aging did not influence sexual differences in cardiac electrophysiological properties, although, it independently prolonged the SCL, PR, and QT intervals, AH and HV intervals, SNRT, AVNERP, and the AV Wenckebach cycle length. The SCL, QRS duration, HV interval, and SNRT were significantly longer in men than in women. Aging prolonged cardiac conduction and increased the SCL but the effects were similar in both sexes. AERP and VERP were unaffected by aging or sex.

Is all ventricular fibrillation the same? Influence of mode of induction on characteristics of ventricular fibrillation.

INTRODUCTION: Little information is available on the relationship between the mode of induction of ventricular fibrillation (VF) to VF characteristics. METHODS AND RESULTS: VF was induced from the anterior left ventricle by programmed electrical stimulation, burst pacing, alternating current (AC), high current S2 at a site remote from S1, T wave shock, and intersecting wavefronts in seven normal dogs and seven dogs with chronic myocardial infarction. Using two electrode arrays, 112 electrograms were recorded from the anterior and lateral wall. Cycle lengths were analyzed and activation vectors were created by summing orthogonally recorded bipolar electrograms. The magnitude of the vector loops was integrated over time to produce an "ensemble vector" index (EVI) whose magnitude is high when beat-to-beat activation direction is consistent and low when activation direction is variable. T wave shock-induced VF had a significantly longer cycle length 1 to 5 seconds after VF onset than other modes of induction (P < 0.05). The frequency-corrected EVI was significantly larger for AC current and T wave shock-induced VF as opposed to all other modes of VF induction in early VF (P < 0.0001). After 10 seconds of VF, these differences persisted only on the anterior wall. CONCLUSION: VF induced in animals by T wave shock and AC current had different characteristics than VF induced by other methods. These findings may have implications for our understanding of VF pathophysiology.

The baculovirus antiapoptotic p35 gene also functions via an oxidant-dependent pathway.

Cellular imbalance in the levels of antioxidants and reactive oxygen species resulting in apoptosis is directly associated with a number of parasitic infections, aging, and several genetic and multifactorial diseases. The baculovirus AcNPV-encoded antiapoptotic p35 gene prevents apoptosis induced by a variety of apoptotic agents in different systems. We demonstrate the ability of the p35 gene to inhibit oxidative stress-induced apoptosis. In vitro cultured Spodoptera frugiperda (Sf9) insect cells infected with wild-type AcNPV carrying the antiapoptotic p35 gene did not undergo apoptosis when subjected to oxidative stress generated by the exogenous application of oxidants or in vivo generation of reactive oxygen species or on direct exposure of cells to UV radiations. An AcNPV mutant carrying a deletion of the p35 gene failed to arrest cell death. Transfection of cells with a recombinant plasmid containing the p35 gene under the transcriptional control of a stress promoter (Drosophila hsp70) was also able to rescue cells from oxidative stress-induced cell death, demonstrating the direct involvement of P35. ESR spin-trapping studies conducted in vitro and in vivo demonstrated that P35 functions directly as an antioxidant by mopping out free radicals and consequently prevents cell death by acting at an upstream step in the reactive oxygen species-mediated cell death pathway.

Intravenous therapy for chronic heart failure exacerbations.

Chronic heart failure (HF) will be the disease of the new millennium. The last decade has seen major developments in the management of HF, with beta-blockers and ACE inhibitors becoming the cornerstones of therapy by virtue of the reductions in total mortality. However, significant gaps remain. Hospitalization for exacerbations of HF are frequent and account for more than 6 million hospital days from this disease related group. Although a variety of intravenous (IV) agents are available for the management of exacerbations of HF, readmission rates are as high as 20%-47% at 6 months. Acute IV therapy for acute decompensation of chronic HF consists of inotropic agents most of which also have vasodilator properties, vasodilator, and diuretics. In addition, there are newer agents in various developmental stages, especially, calcium sensitizing drugs, vasopressin receptor antagonists, and natriuretic peptides. Despite the multiplicity of agents, there are no well designed, randomized, placebo controlled trials to guide IV inpatient therapy for HF exacerbations. (c)1999 by CHF, Inc.

Reproducibility of ventricular fibrillation characteristics in patients undergoing implantable cardioverter defibrillator implantation.

INTRODUCTION: The purpose of this study was to evaluate the immediate reproducibility of local electrogram characteristics recorded during repeated episodes of induced ventricular fibrillation (VF) in patients undergoing implantable cardioverter defibrillator (ICD) implantation. METHODS AND RESULTS: Power spectral analysis (using a fast Fourier transform algorithm) of electrograms recorded during 3 seconds of VF were analyzed in 24 patients undergoing ICD implantation using a Medtronic Transvene lead. Patients had 2 to 7 episodes of VF that were induced during defibrillation threshold testing. VF was induced by burst pacing (n = 20) or T wave shock (n = 4). Simultaneous electrograms during VF were recorded from a Medtronic Transvene lead with the following configurations: (1) a narrow spaced (12 mm) dedicated bipole used clinically for sensing; (2) a unipolar electrogram from the right ventricular coil; and (3) a widely spaced (18.3 mm) integrated bipole using the distal tip and the coil. Intraclass correlation coefficients (ICCs) were determined to examine the reproducibility of these VF characteristics among VF episodes in each patient. Recordings from both bipolar configurations had ICCs from 0.40 to 0.55, whereas unipolar recordings ICCs were below 0.40. Reproducibility was similar for dedicated and integrated recordings. CONCLUSIONS: Frequency characteristics of repeated episodes of VF induced in the same subjects show fair-to-good but not excellent reproducibility. Bipolar recordings were far more reproducible than unipolar recordings, but both bipolar configurations had similar reproducibility. These findings have implications for both the pathophysiology of induced VF and the design of VF detection algorithms.