No long-term tunnel enlargement following anterior cruciate ligament reconstruction using autograft hamstring tendon with dual suspensory fixation.

PURPOSE: Bone tunnel widening following anterior cruciate ligament reconstruction (ACLR) is well documented, although the aetiology and clinical significance of this phenomenon remain unclear. At mid-term follow-up, a greater prevalence of tunnel enlargement has been reported with the use of hamstring (HS) grafts. However, there are paucity of data on what happens in the longer term. The aim of this study was to assess the change in femoral and tibial tunnel dimensions 15 years after four-strand HS ACLR. METHODS: This is a retrospective review of 15 patients who underwent arthroscopic ACLR using HS autograft tendon and were followed up radiographically at 4 months, 2 years and 15 years. Suspensory fixation was used for both ends of the graft. The diameters of the bone tunnels on posteroanterior (PA) and lateral radiographs were measured using digital callipers. Repeated measures analysis of variance (ANOVA) was used to examine change in tunnel width over time. RESULTS: Radiographic tunnel width did not significantly change between 4 months and 2 years. However, a significant decrease in width was found for both the femoral and tibial tunnels between the 2- and 15-year follow-up (P < 0.01): the femoral tunnel decreased by 50% and 51% in the PA and lateral views, respectively; the tibial tunnel decreased by 77% and 91% in the PA and lateral views respectively. There was no significant correlation between femoral or tibial tunnel width and flexion and extension deficits or with side to side differences in anterior tibial laxity at 15 years. CONCLUSIONS: This radiographic follow-up study of bone tunnel widening following HS ACLR with suspensory fixation demonstrated that tunnel width did not increase beyond 4 months and in fact had decreased significantly at long-term (15 years) follow-up. There was no correlation between tunnel width changes and clinical assessment of flexion and extension deficits or with side-to-side anterior knee laxity at 15-years. LEVEL OF EVIDENCE: IV.

Focal laser ablation as clinical treatment of prostate cancer: report from a Delphi consensus project.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

Retrospective study found that outpatient care for infants exposed to drugs during pregnancy was sustainable and safe.

AIM: We determined the safety, feasibility and sustainability of an outpatient model of care for infants exposed to intra-uterine drugs. METHODS: This was a retrospective chart review of 774 drug-exposed infants born between 1998 and 2016 at the Royal Hospital for Women, Sydney, Australia. RESULTS: Most (86%) of the mothers used multiple drugs, including opioids (58%). More than three-quarters (78%) of the infants were born full term at a mean gestation of 38 weeks and hospitalised for a median of seven days. This rose to 14 days if they were medicated for neonatal abstinence syndrome (NAS). Most of the NAS patients (83%) were discharged on medication, namely morphine, and the median duration of NAS treatment was 76 (interquartile range 35-120). Three medication errors occurred: two extra doses of phenobarbitone and one infant weaned off morphine faster than prescribed. No infants were rehospitalised for NAS. Four died from sudden infant death syndrome at 2.2-5.8 months after discharge and one drowned at 15 months. None were medicated at the time of death. CONCLUSION: Outpatient care for drug-exposed infants was sustainable and had low complication rates, even for those with NAS. The optimum duration of follow-up and impact on hospital costs should be examined.

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project.

PURPOSE: To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). METHODS: An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. RESULTS: mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. CONCLUSIONS: The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.

Post-discharge oral antimicrobial use among hospitalized patients across an integrated national healthcare network.

OBJECTIVES: Antimicrobial stewardship programmes have focused on reducing inappropriate inpatient antimicrobial prescribing, but several small studies have found a large portion of antimicrobial exposure occurs immediately after hospital discharge. In this study, we describe the prescribing of oral antimicrobials at hospital discharge across an integrated national healthcare system. At the hospital level, we also compare total inpatient antimicrobial use and post-discharge oral antimicrobial use. METHODS: This retrospective cross-sectional study used national administrative data to identify all acute-care admissions during 2014-2016 within the Veterans Health Administration (VHA). We evaluated inpatient days of therapy (DOT) and post-discharge DOT, defined as oral outpatient antimicrobials dispensed at the time of hospital discharge. At the hospital level, inpatient DOT/100 admissions were compared with post-discharge DOT/100 admissions using Spearman's rank-order correlation. RESULTS: There were 1 681 701 acute-care admissions across 122 hospitals, and 335 369 (19.9%) were prescribed an oral antimicrobial at discharge. Fluoroquinolones (38.3%) were the most common post-discharge antimicrobial. At the hospital level, median inpatient antimicrobial use was 331.3 (interquartile range (IQR) 284.9-367.9) DOT/100 admissions and median post-discharge use was 209.5 (IQR 181.5-239.6) DOT/100 admissions. Thirty-nine per cent of the total duration of antimicrobial exposure occurred after discharge. At the hospital-level, the metrics of inpatient DOT/100 admissions and post-discharge DOT/100 admissions were weakly positively correlated with rho=0.44 (p < 0.001). CONCLUSIONS: A large proportion of antimicrobial exposure among hospitalized patients occurred immediately following discharge. Antimicrobial-prescribing at hospital discharge provides an opportunity for antimicrobial stewardship. Hospital-level stewardship metrics need to include both inpatient and post-discharge antimicrobial-prescribing to provide a comprehensive assessment of hospital-associated antimicrobial use.

Fragile X mental retardation protein replacement restores hippocampal synaptic function in a mouse model of fragile X syndrome.

Fragile X syndrome (FXS) is caused by a mutation that silences the fragile X mental retardation gene (FMR1), which encodes the fragile X mental retardation protein (FMRP). To determine whether FMRP replacement can rescue phenotypic deficits in a fmr1-knockout (KO) mouse model of FXS, we constructed an adeno-associated virus-based viral vector that expresses the major central nervous system (CNS) isoform of FMRP. Using this vector, we tested whether FMRP replacement could rescue the fmr1-KO phenotype of enhanced long-term depression (LTD), a form of synaptic plasticity that may be linked to cognitive impairments associated with FXS. Extracellular excitatory postsynaptic field potentials were recorded from CA3-CA1 synaptic contacts in hippocampal slices from wild-type (WT) and fmr1-KO mice in the presence of AP-5 and anisomycin. Paired-pulse low-frequency stimulation (PP-LFS)-induced LTD is enhanced in slices obtained from fmr1 KO compared with WT mice. Analyses of hippocampal synaptic function in fmr1-KO mice that received hippocampal injections of vector showed that the PP-LFS-induced LTD was restored to WT levels. These results indicate that expression of the major CNS isoform of FMRP alone is sufficient to rescue this phenotype and suggest that post-developmental protein replacement may have the potential to improve cognitive function in FXS.

A prospective longitudinal study to assess psychological changes following anterior cruciate ligament reconstruction surgery.

OBJECTIVE: To determine whether the psychological characteristics of athletes who have undergone an anterior cruciate ligament (ACL) reconstruction change during rehabilitation are related to returning to competitive sport. DESIGN: Prospective longitudinal study. METHOD: 87 athletes completed the Emotional Response of Athletes to Injury Questionnaire (ERAIQ) and the ACL Return to Sport after Injury scale (ACL-RSI) at 3, 6 and 12 months following ACL reconstruction surgery. Physical outcome measures were also taken at each time point. RESULTS: At 12 months 44 (51%) participants had returned to competitive sport and 43 (49%) participants had not returned. There were no differences in physical recovery or scores on the ERAIQ between the two groups. Participants who had returned to competitive sport at 12 months, however, scored significantly higher on the ACL-RSI scale (reflecting a more positive psychological response about sport participation) at both 6 and 12 months than participants who had not returned to competitive sport. CONCLUSIONS: During rehabilitation there are significant psychological differences regarding sport resumption between athletes who do, and do not, resume competitive sport 12 months following ACL reconstruction. These differences occur as early as 6 months postoperatively and highlight the importance of addressing all aspects of an athlete's recovery in order to help facilitate the athlete returning to sport.

Manganese release linked to carbonate dissolution during the start-up phase of a subsurface iron removal well in Khabarovsk, Russia.

Subsurface iron removal (SIR) is a proven pre-treatment technology for removing dissolved iron and manganese from groundwater. The start-up phase of a SIR well and the proper development of the reaction zone around the well are crucial for its subsequent performance. This study evaluates the start-up phase of a SIR production well in Khabarovsk, Russia during the first 194 SIR cycles. A strong release of manganese was observed, which led to concentrations twice as high as the background value of the pristine groundwater. Regular monitoring of the production well and its three adjacent observation wells showed that iron removal began immediately after start-up and that the reaction zone was completely formed within 25 SIR cycles. Closed-bottle batch tests and a flow-through leaching test revealed that the grain size of the aquifer material and groundwater pH are the primary controls on manganese release. During infiltration phases the dissolution of manganese-bearing carbonate minerals was caused by direct oxidation by O2, whereas the low groundwater pH of 6 seemed to be responsible for the manganese release during extraction.

Impact of combined C1 esterase inhibitor/coagulation factor XIII or N-acetylcysteine/tirilazad mesylate administration on leucocyte adherence and cytokine release in experimental endotoxaemia.

We determined the effects of combinations of C1 esterase inhibitor (C1-INH) with factor XIII and of N-acetylcysteine (NAC) with tirilazad mesylate (TM) during lipo-polysaccharide (LPS)-induced endotoxaemia in rats. Forty Wistar rats were divided into four groups: the control (CON) group received no LPS; the LPS, C1-INH + factor XIII and NAC + TM groups received endotoxin infusions (5 mg/kg per h). After 30 min of endotoxaemia, 100 U/kg C1-INH + 50 U/kg factor XIII was administered to the C1-INH + factor XIII group, and 150 mg/kg NAC + 10 mg/kg TM was administered in the NAC + TM group. Administration of C1-INH + factor XIII and NAC + TM both resulted in reduced leucocyte adherence and reduced levels of interleukin-1beta (IL-1beta). The LPS-induced increase in IL-6 levels was amplified by both drug combinations. There was no significant effect on mesenteric plasma extravasation. In conclusion, the administration of C1-INH + factor XIII and NAC + TM reduced endothelial leucocyte adherence and IL-1beta plasma levels, but increased IL-6 levels.

Kinematic patterns associated with accuracy of the drop punt kick in Australian Football.

Research into the kinematics of movement associated with the accuracy of the drop punt kick in Australian Football has been limited. The aim of this study was to examine pelvic and lower limb kinematics during the performance of a drop punt kick, in order to identify factors associated with accurate kicking performance. Ten professional Australian Football League (AFL) players performed 20 drop punt kicks towards a target situated 15m away, using their preferred leg. A three-dimensional motion analysis system was used to record the kicking motion from heel contact of the support limb through to ball contact. The subjects were divided into an accurate group (> or =50% accuracy; n=5) and an inaccurate group (<50% accuracy; n=5) based on target hit rate. Kinematic profiles for both kicking and support limbs were compared between the two groups. Results showed that the accurate group had significantly greater hip flexion in both limbs and greater knee flexion in the support limb throughout the kicking movement. The accurate group also had significantly greater anterior pelvic tilt at heel contact (accurate 20.8 degrees ; inaccurate 12.7 degrees ). These data show that kinematic differences in lower limb joint angles may be related to kicking accuracy.

A preliminary report of the efficacy of Debrisan (dextranomer) in the debridement of cutaneous ulcers.

A randomized trial involving 50 patients has demonstrated that a new type of debriding agent, cross-linked dextran beads with the trade name Debrisan (dextranomer, Pharmacia, Inc.), will produce rapid healing of cutaneous ulcers which have been resistant to conventional therapy over the long-term. Evaluation in terms of a number of therapeutic parameters, including rate of healing, dehydration, sterilization, loss of symptoms, and improvement in physiology, is included in this preliminary study.

Abnormal tenocyte morphology is more prevalent than collagen disruption in asymptomatic athletes' patellar tendons.

This study investigated the prevalence of each of the four features of patellar tendinosis in asymptomatic athletic subjects undergoing patellar tendon anterior cruciate ligament (ACL) reconstruction. Fifty subjects (39 males and 11 females) undergoing ACL reconstruction using a patellar tendon graft were screened for previous tendon symptoms, training and playing history and had their patellar tendons examined with ultrasound prior to surgery. During surgery, a small piece of proximal posterocentral tendon was harvested, fixed and examined under light microscopy. Histopathological changes were graded for severity. Results demonstrate that 18 tendons were abnormal on light microscopy and 32 were normal. There were no differences between subjects with and without pathology in respect of training, recovery after surgery and basic anthropometric measures. Three tendons were abnormal on ultrasound but only one had proximal and central changes. Tendons showed a consistent series of changes. Tenocyte changes were found in all but one of the abnormal tendons. In all but one of the tendons with increased ground substance there were tenocyte changes, and collagen separation was always associated with both tenocyte changes and increased ground substance. No tendons demonstrated neovascularization. It appears that cellular changes must be present if there is an increase in ground substance, or collagen and vascular changes. Further research is required to confirm these findings.

Construction of recombinant vaccinia virus expressing HCV genes.

Hepatitis C virus (HCV) remains the leading cause of non-A, non-B hepatitis, and a major indicator for orthotopic liver transplantation. To date, finding a cure or even a commonly effective therapy for infection with HCV has proven to be an elusive goal. One major problem that has hampered attempts to develop antiviral agents is the ongoing inability to grow the virus in tissue culture. Without an efficient in vitro system for the propagation of HCV, it is difficult to generate the large amounts of viral protein needed for this sort of study; nor can the effects of known antiviral agents be assessed on the replication of HCV. Recently, some laboratories have reported preliminary evidence of HCV replication in cultured cells (1,2), but even the best of these systems does not produce significant amounts of progeny virus. Although these methods may be applicable in the future, at present they are not yet practical.

Use of a discistronic vector for the quantitation of HCV IRES activity.

The 5'-untranslated region of hepatitis C virus (HCV) has been shown to function as an internal ribosomal entry site, or IRES. The biological function of the HCV IRES has been shown to be essential for initiation of translation of the viral proteins by host ribosomes. With this critical role in HCV replication, the IRES makes an attractive target for the development of antiviral compounds Furthermore, since eukaryotic translation is not initiated via an IRES, agents that specifically interfere with function of the HCV IRES may be relatively nontoxic to the host Fundamental to the testing of any of these antivirals is a system to evaluate their efficacy. This chapter describes the use of a dicistromc vector in an in vitro system to assess the translational initiation efficiency of isolated HCV IRES elements.

Patellar resurfacing versus retention in total knee arthroplasty.

We studied 40 patients in whom the patella was not severely deformed and who were undergoing primary total knee arthroplasty (TKA) for osteoarthritis by one surgeon using one type of prosthesis. They were randomly allocated either to have the patella retained or resurfaced with a cemented, all-polyethylene component regardless of the state of the patellar articular cartilage. Apart from removal of osteophytes, no surgery was undertaken on the retained patellae. All 38 surviving patients were evaluated at three years using the HSS knee score and a new, specifically designed Patellar score (maximum score of 30). No TKA was revised, but two patients in the resurfacing group had a further unrelated procedure. The mean HSS and Patellar scores at follow-up were 89 and 28 in the patellar retention group and 83 and 26 in the patellar resurfacing group. Statistically significant lower scores for both were recorded in women and in heavier patients. Stair-climbing ability was significantly better in the retention group. Although there were no complications related to patellar resurfacing, in the medium term we did not find any significant benefit from resurfacing the patella during TKA for osteoarthritis if it was not severely deformed.

MR arthrography of the shoulder.

Although conventional MR imaging allows direct visualization of major anatomic structures, smaller intraarticular structures, including the glenoid labrum, glenohumeral ligaments, and articular surface of the rotator cuff tendon can be difficult to evaluate in the absence of a joint effusion. The authors review the techniques employed in performing MR arthrography, imaging characteristics of MR arthrography, and diagnostic utilization of the technique. Suggested indications are provided.

Clinical value of magnetic resonance imaging of the knee.

BACKGROUND: Magnetic resonance (MR) imaging is an accurate imaging modality of the knee. The role of MR in clinical practice has not been precisely defined, largely due to the relative expense of the technique. METHODS: For each new patient with a knee problem who was referred for MR, a provisional diagnosis was made together with a level of certainty regarding the diagnosis. The waiting time for the scan was recorded. To assess clinical usefulness the MR diagnosis was compared with the provisional diagnosis and classified according to the following descending order of value: unexpected negative (no intra-articular pathology), confirmatory negative, unexpected positive or confirmatory positive. To assess accuracy of the MR diagnosis, the operative diagnosis was compared to the MR diagnosis in those patients who underwent arthroscopy. RESULTS: Fifty-two per cent of scans were assessed as being very useful and a further 20% were assessed as being moderately useful. Magnetic resonance had a 95% accuracy for medial meniscal tears, 91% accuracy for lateral meniscal tears, and 98% accuracy for anterior cruciate ligament tears, similar to previously reported studies. The diagnostic arthroscopy rate in the patients who underwent MR scanning was similar to that in patients for whom the surgeon was more confident about the diagnosis and who therefore did not undergo MR scanning. The diagnostic arthroscopy rate could have been reduced if surgery had not been performed in 14 patients who had a negative MR scan. CONCLUSIONS: There is a role for selective use of MR in the assessment of knee conditions. In particular, MR can be used to reduce the diagnostic arthroscopy rate.

New approaches in the therapy of the peripheral vascular ulcer.

It can readily be seen that Debrisan represents a more effective mode of therapy for several groups of patients which tend to have chronic disabling ulcers of limbs of various etiologies, including venous stasis ulcers, chronic sickle-cell ulcers, decubiti, etc. The more effective treatment of this patient populations, which is provided by Debrisan, would provide a very significant decrease in the total cost of health care in the United States, approximating half a billion dollars per year.

The effect of gas loading on the RUS spectra of spheres

Resonant Ultrasound Spectroscopy (RUS) of a spherical sample in a pressurizing gas atmosphere was investigated experimentally and theoretically. Measurements were made on a fused silica sphere in He, Ar, and N2 gases up to pressures of 120 bar. The pressure-dependent shift in the resonant frequency, delta f, and the Q-factor were measured for the S00, S11, and T02 modes. A theoretical model based on acoustic radiation impedance was used to calculate delta f and the radiation-resistance component, Qr, of the Q-factor. Agreement between theory and experiment was good for Qr, but there were discrepancies for delta f. It was found that the theoretical delta f due to gas-loading effects associated with acoustic radiation was very small and consistent with the observed dependence on pressure and gas species for the T02 mode but not for the S00 and S11 modes. We conclude that the T02 mode is the most reliable of these modes to use in measuring third-order elastic constants by RUS.

Evaluation of swinepox virus as a vaccine vector in pigs using an Aujeszky's disease (pseudorabies) virus gene insert coding for glycoproteins gp50 and gp63.

Pigs were vaccinated by scarification or intramuscular injection with a swinepox virus-Aujeszky's disease (pseudorabies) recombinant (rSPV-AD) constructed by inserting the linked Aujeszky's disease virus genes coding for glycoproteins gp50 and gp63, attached to a vaccinia virus p7.5 promoter, into the thymidine kinase gene of swinepox virus. By 21 days after vaccination, 90 and 100 per cent of the animals vaccinated by scarification or intramuscular injection, respectively, had developed serum neutralising antibodies to Aujeszky's disease virus. Upon challenge with virulent virus, significantly fewer vaccinated pigs developed clinical Aujeszky's disease, nasal shedding of challenge virus was markedly reduced, and the vaccinated groups of pigs maintained or gained weight during the week after challenge whereas the unvaccinated control group lost weight. No transmission of rSPV-AD to in-contact controls was detected during the three weeks before challenge. In a second experiment, serum neutralising antibodies to Aujeszky's disease virus persisted for 150 days after the pigs were vaccinated with rSPV-AD by scarification or intramuscular injection and all the pigs showed an anamnestic response when they were revaccinated.