Long-term functional success and patient-reported outcomes after female one-stage buccal mucosal graft urethroplasty.

INTRODUCTION AND OBJECTIVES: Female urethral strictures are a rare condition that significantly impacts patients' quality of life. Patient-reported outcomes are crucial, yet data regarding sexual function and treatment satisfaction are scarce. We aimed to provide insights from a reconstructive referral center. PATIENTS AND METHODS: We conducted a retrospective analysis of women treated with ventral onlay one-stage buccal mucosa graft urethroplasty for urethral strictures between 2009-2023. We assessed objective (retreatment-free survival, ΔQmax) and subjective outcomes (validated patient-reported outcomes). RESULTS: Of 12 women, 83% and 17% had iatrogenic and idiopathic strictures, respectively. Median number of prior interventions was 6. Strictures were located meatal and mid-urethral in 25% and 75%, respectively, 22% had the bladder neck involved. Median graft length was 2 cm. At median follow-up of 66 months, 33% of patients underwent stricture retreatment, but only one case occurred within the first 2 years postoperatively. The median improvement in maximum flow rate (ΔQmax) was 10 ml/s. Median International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS) scores were 8 for filling symptoms, 6 for voiding symptoms, and 3 for incontinence symptoms. Median ICIQ-FLUTSsex score was 4. Higher scores indicate a higher symptom burden. Median ICIQ-Satisfaction outcome and satisfaction scores were 18 and 7, respectively, reflecting high treatment satisfaction. CONCLUSIONS: Buccal mucosal graft urethroplasty by ventral onlay for female urethral strictures yields effective, durable, and positively received outcomes. However, larger studies across multiple institutions are necessary to further assess its efficacy, especially regarding patient-reported experiences and sexual function.

Mortality and mental health funding-do the dollars add up? Eating disorder research funding in Australia from 2009 to 2021: a portfolio analysis.

Background: Eating Disorders (EDs) are among the deadliest of the mental disorders and carry a sizeable public health burden, however their research and treatment is consistently underfunded, contributing to protracted illness and ongoing paucity of treatment innovation. Methods: We compare absolute levels and growth rates of Australian mental health research funding by illness group for the years 2009-2021, with a specific focus on eating disorders analysed at the portfolio level. Findings: Actual and adjusted data obtained from Australia's three national medical research funding bodies (NHMRC, ARC and MRFF) shows eating disorders receive a disproportionately low allocation of mental health research funding despite having amongst the highest mortality rates. Forty-one category one research grants totalling $AUD28.1 million were funded for eating disorders over the period. When adjusted for inflation, this equates to $2.05 per affected individual, compared with $19.56 for depression, $32.11 for autism, and $176.19 for schizophrenia. Half of all research funded for eating disorders was 'basic' research (e.g., illness underpinning), with little investment in the development of innovative treatment models, novel therapeutics or translation, well reflected by recovery rates of less than 50% in individuals with Anorexia Nervosa. Interpretation: Significant discrepancy remains between research funding dollars and disease burden associated with the mental health disorders. The extent to which eating disorders are underfunded may in part be attributable to inaccuracies in epidemiological and burden of disease data. Funding: This work was in-part funded by the Australian Government Department of Health and the National Eating Disorder Research & Translation Strategy. The funder was not directly involved in informing the development of the current study.

Development of an intervention to manage knee osteoarthritis risk and symptoms following anterior cruciate ligament injury.

INTRODUCTION: Anterior cruciate ligament (ACL) injury is a risk factor for developing knee osteoarthritis (OA). We developed an intervention to support people manage risk factors for OA. METHODS: We conducted one-on-one interviews with 20 individuals with OA symptoms 6-15 years post ACL injury and used a nominal group process during a workshop with 40 patients and healthcare professionals (HCPs) to elicit information on the intervention content and delivery characteristics (timing, HCPs, and methods). Interview data were analyzed using content analysis. Nominal group ideas with importance ratings ≥5 of 7 met criteria for inclusion. Results were integrated, considering similarities and differences. RESULTS: Eight content categories were identified: 1. understanding knee injury and expectations about recovery; 2. understanding OA risk; 3. understanding OA signs and symptoms; 4. managing OA risk; 5. managing knee OA symptoms; 6. information for influencers; 7. credible sources; and, 8. updates on new evidence and treatments. Delivery timing reflected a lifespan approach from time of injury through symptomatic knee OA management. Although multiple media for delivery were identified, introductory face-to-face discussions and opportunity for re-accessing HCPs were critical. All HCPs who treat people with ACL should be familiar with and able to deliver the intervention. CONCLUSIONS: This co-development approach identified that an intervention to support people with ACL injury to limit and manage knee OA requires content embedded within an easily accessible, multi-media delivery model with capacity for check-back with HCPs that is appealing to different age groups and personal preferences over the lifespan post injury.

[Vesicovaginal fistulas: diagnosis and surgical management]. / Vesikovaginale Fisteln: Diagnostik und operatives Management.

Vesicovaginal fistulas (VVF) represent a detrimental condition causing psychological, physical and social strain on patients. In developed countries they are predominantly the result of pelvic surgery or radiation therapy, whilst obstetric VVF are common in developing countries due to prolonged and complicated births. The majority of VVF require surgical therapy, thus a comprehensive diagnostic workup is needed. Depending on diagnostic characteristics fistula repair can be performed by a transvaginal, transabdominal or minimally invasive approach. Timing of surgery, appropriate interposition of vascularized grafts, optimized postoperative management and surgical expertise are determining factors for successful treatment. This review describes the diagnostic workup and therapeutic management of VVF including various surgical techniques.

Guidance on prevention of unintended and accidental radiation exposures in nuclear medicine.

Nuclear medicine (NM) procedures for diagnosis and treatment of disease are performed routinely in hospitals throughout the world. These involve preparation and administration to patients of pharmaceuticals labelled with radioactive material. The International Atomic Energy Agency (IAEA) and the World Health Organisation highlighted the need for improvement in prevention of medical radiation incidents and accidents in the Bonn Call-for-Action in 2012. An IAEA Technical Meeting was held on prevention of unintended exposures and accidents in NM in 2018 to address the issue. Exposures can take place at any time when radioactive material is being produced and used, and the risk continues after procedures have been completed. Thus there is potential for staff or members of the general public to be exposed, as well as patients. This paper sets out guidelines for incident prevention based on presentations and discussions at the meeting, and review of reports from the literature. It deals with potential incidents in in-house radionuclide production, radiopharmaceutical preparation, administration to patients, and following a procedure, as well as aspects in management of radioactive materials. Special attention has been paid to therapeutic procedures, as these have the potential to cause more harm to patients from erroneous administrations, including tissue reactions from extravasation of radiopharmaceutical, and could lead to significant contamination events. Administration of NM therapy is generally contraindicated in pregnancy. Identification of any patient who may be pregnant is crucial and it might be necessary to verify this with a pregnancy test for patients within the age band considered to be fertile. Inclusion of NM therapy incidents in the IAEA automated reporting system SAFRON is recommended. In summary, the paper aims to highlight errors that could occur during different phases of NM procedures in order to aid prevention of incidents. The value of periodic audit in evaluating systems in place on a regular basis is emphasised. Approaches to incident investigation and follow-up are described, and the need to ensure corrective action is taken to address any deficiencies stressed.

Shortened therapy of eight weeks with paritaprevir/ritonavir/ombitasvir and dasabuvir is highly effective in people with recent HCV genotype 1 infection.

Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved for treatment of chronic HCV genotype 1 infection. This study assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks among people with recent HCV infection. In this open-label single-arm trial conducted in Australia, England and New Zealand, adults with recent HCV (duration of infection <12 months) received paritaprevir/ritonavir/ombitasvir and dasabuvir (with weight-based ribavirin for genotypes 1a and 1, no subtype) for 8 weeks. The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) population. Thirty people (median age 38 years, male 93%) commenced treatment (with ribavirin, 97%), of whom 77% (n = 23) were HIV-positive, 93% (n = 28) had genotype 1a infection and 53% (n = 16) had ever injected drugs. Median maximum ALT in the preceding 12 months was 433 IU/L (IQR 321, 1012). Acute clinical hepatitis with ALT > 10 x ULN was documented in 83% (n = 25); one participant (3%) had jaundice. At baseline, median estimated duration of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log10 IU/mL (range 2.7, 7.3). SVR12 was achieved in 97% (29/30; early discontinuation at week 2, n = 1; per protocol 100%, 29/29). No relapse or reinfection was observed. In conclusion, paritaprevir/ritonavir/ombitasvir and dasabuvir (with ribavirin) for eight weeks were highly effective among HIV-positive and HIV-negative individuals with recent HCV infection. These data support the use of this shortened duration direct-acting antiviral regimen in this population.

Ultrasound Determination of the Femoral Head-Neck Alpha Angle.

The femoral head-neck alpha angle is used to quantify the degree of femoral head asphericity in patients suspected of cam-type femoroacetabular impingement. The measurement was first performed using magnetic resonance imaging and, more recently, three-dimensional computed tomography (CT). We set out to determine whether the alpha angle could be reliably measured using ultrasound. Patients were recruited from a cohort presenting for CT of the hip. Alpha angles were calculated following the departmental protocol by institutionally accredited radiographers. After the CT, patients were imaged with ultrasound and the alpha angle calculated from the ultrasound image by a sonographer blinded to the CT result. Statistical comparison of the two methods was performed with the Bland-Altman test using SPSS (version 21.0, Chicago, USA), and a p < 0.05 afforded significance. Twenty-eight patients were recruited. Eleven patients were bilateral examinations, providing 39 hips for analysis. There were 15 females and 13 males, with 21 right and 18 left hips examined. Average patient age (±standard deviation) was 40 y (±13.9 y). Mean (±standard deviation) measurements for CT and ultrasound were 62.5° (±14.2°) and 64.5° (±12.6°), respectively. The mean absolute difference between the two methods was 10.5° (95% confidence interval 6.9°-14.0°). Sensitivity of each individual ultrasound measurement was 91.3%. The specificity of ultrasound was 43.75%. The positive predictive value was 0.7, and the negative predictive value was 0.78. Overall accuracy of the ultrasound-derived alpha angle was calculated at 0.718. Ultrasound demonstrates good sensitivity and good negative predictive value in calculation of the femoral head-neck alpha angle compared with CT; however, specificity is low. Ultrasound measurement of the alpha angle can provide objective evidence of cam-type femoroacetabular impingement in symptomatic patients and can direct patients to more established imaging techniques where appropriate.

Modeling complete removal of risk assessment questions in the USA predicts the risk of HIV exposure in blood recipients could increase despite the use of nucleic acid testing.

BACKGROUND AND OBJECTIVES: The safety of the blood supply in a number of countries is achieved by interventions that include behaviour-based time-limited or indefinite deferrals and screening of donated units for transfusion-transmitted infections. The relatively high sensitivity of nucleic acid testing (NAT) used in blood donor screening has raised the question of whether such time-based deferrals can be eliminated in favour of individual risk assessment. MATERIALS AND METHODS: Data on the annual number of incident human immunodeficiency virus (HIV) infections associated with various behaviours and on the performance characteristics of NAT applied to donor screening were used to model the number of potentially infected units that might escape detection in the worst-case scenario in which individual risk assessment was implemented, but was not effective as a screening tool, and donors did not otherwise self-select for lower risk. RESULTS: In the absence of effective individual risk-based screening or donor self-selection, the model predicts that in the United States, an additional 39 (95% CI 35-43) HIV-infected units would escape detection by nucleic acid testing, potentially capable of exposing approximately 68 (95% CI 61-75) individuals to the risk of HIV infection through the administration of prepared blood components. CONCLUSION: Despite some inherent uncertainty, the worst-case scenario of completely ineffective individual risk assessment, absence of donor self-selection and increased reliance on NAT for blood screening is estimated to be associated with an approximately fourfold increase in the risk of HIV exposure through transfusion in the United States.

Evidence of dose saving in routine CT practice using iterative reconstruction derived from a national diagnostic reference level survey.

OBJECTIVE: To assess the influence and significance of the use of iterative reconstruction (IR) algorithms on patient dose in CT in Australia. METHODS: We examined survey data submitted to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) National Diagnostic Reference Level Service (NDRLS) during 2013 and 2014. We compared median survey dose metrics with categorization by scan region and use of IR. RESULTS: The use of IR results in a reduction in volume CT dose index of between 17% and 44% and a reduction in dose-length product of between 14% and 34% depending on the specific scan region. The reduction was highly significant (p < 0.001, Wilcoxon rank-sum test) for all six scan regions included in the NDRLS. Overall, 69% (806/1167) of surveys included in the analysis used IR. CONCLUSION: The use of IR in CT is achieving dose savings of 20-30% in routine practice in Australia. IR appears to be widely used by participants in the ARPANSA NDRLS with approximately 70% of surveys submitted employing this technique. ADVANCES IN KNOWLEDGE: This study examines the impact of the use of IR on patient dose in CT on a national scale.

Australian per caput dose from diagnostic imaging and nuclear medicine.

The largest man-made contributor to the ionising radiation dose to the Australian population is from diagnostic imaging and nuclear medicine. The last estimation of this dose was made in 2004 (1.3 mSv), this paper describes a recent re-evaluation of this dose to reflect the changes in imaging trends and technology. The estimation was calculated by summing the dose from five modalities, computed tomography (CT), general radiography/fluoroscopy, interventional procedures, mammography and nuclear medicine. Estimates were made using Australian frequency data and dose data from a range of Australian and international sources of average effective dose values. The ionising radiation dose to the Australian population in 2010 from diagnostic imaging and nuclear medicine is estimated to be 1.7 mSv (1.11 mSv CT, 0.30 mSv general radiography/fluoroscopy, 0.17 mSv interventional procedures, 0.03 mSv mammography and 0.10 mSv nuclear medicine). This exceeds the estimate of 1.5 mSv per person from natural background and cosmic radiation.

Relapsing and remitting severe hypoglycemia due to a monoclonal anti-insulin antibody heralding a case of multiple myeloma.

CONTEXT: We report a novel case of insulin autoimmune syndrome (IAS) presenting with hypoglycemia due to production of a monoclonal anti-insulin antibody in a patient subsequently found to have multiple myeloma (MM). OBJECTIVE: The aim of the study was to describe the 5-yr clinical course of a patient with IAS and MM and to characterize the origin and function of the pathogenic antibody. METHODS: We conducted a longitudinal case history with laboratory investigations to characterize the anti-insulin antibody subtype, specificity, affinity, and origin. RESULTS: The patient presented with IAS, which worsened during treatment of hepatitis C. The patient was then discovered to have a monoclonal gammopathy that progressed to MM. Treatment of the MM induced remission of the neoplasia and IAS, which then followed a synchronized course of progression and response to therapy. An anti-insulin IgG(3)-λ that bound specifically but with low affinity to the insulin B chain (amino acids 9-30) and that was distinct from the primary MM IgG(3)-κ clone was recovered from the patient and cloned. The antibody bound insulin and showed mutations of normal affinity maturation. CONCLUSIONS: We describe a case of MM heralded by IAS, where full characterization of the pathogenic antibody revealed that the monoclonal anti-insulin antibody had originated from a self-reactive clone.

Serum non-coding RNAs as biomarkers for osteoarthritis progression after ACL injury.

OBJECTIVE: The aim of this study was to examine serum non-coding RNAs as potential biomarkers for cartilage damage associated with anterior cruciate ligament (ACL) injury. METHODS: Serum was obtained from 80 patients 1 year after surgery for ACL injury and 60 normal donors without overt skeletal injury. Total serum RNA was isolated, small non-coding RNAs profiled by TaqMan array MicroRNA (miRNA) analysis and individual small RNA assays performed by quantitative TaqMan RT-PCR (qPCR). Semi-quantitative magnetic resonance imaging (MRI) analysis was performed using Whole Organ Magnetic Resonance Knee Score (WORMS) scoring for analysis of cartilage damage. RESULTS: Initial TaqMan array miRNA profiling showed an increased serum concentration of a small nucleolar RNA (snoRNA), U48, in five patients with cartilage damage compared with that in five patients without cartilage damage and six normal donors. Independent qPCR analysis of snoRNAs in serum from all patients and normal donors showed a strong association between the serum level of another snoRNA, U38, and cartilage damage in ACL injury patients and together with snoRNA, U48, clear distinction between ACL injury patients and normal donors. CONCLUSION: SnoRNAs U38 and U48 are significantly elevated in the serum of patients developing cartilage damage at 1 year after ACL injury. Serum levels of U38 have the potential to facilitate early diagnosis of patients with cartilage damage after ACL injury. This study suggests serum non-coding RNAs may serve as novel noninvasive biomarkers for the detection and assessment of cartilage damage after ACL injury.

The effect of the sitting upright or 'beachchair' position on cerebral blood flow during anaesthesia for shoulder surgery.

The sitting upright or 'beachchair' position is commonly used for shoulder arthroscopic surgery. There is a theoretical concern that anaesthetised patients placed in this posture are at risk of reduced cerebral blood flow (CBF), especially if there is associated hypotension. This study investigated the effect of anaesthetic-induced hypotension on estimated cerebral blood flow in patients placed in the beachchair position for shoulder surgery. Forty patients were randomised to either sedation (propofol infusion 10 to 20 mg x hour 1, n = 20) or general anaesthesia using sub minimum alveolar concentration of sevoflurane (n = 20). All patients received an interscalene brachial plexus regional block. Internal carotid artery blood flow was measured using the time averaged velocity of the spectral Doppler waveform, and was then used as an estimate of global CBF. Following a pre-anaesthesia study, measurement of internal carotid artery blood flow was made before and after beachchair positioning, and at five-minute intervals during surgery. Beachchair positioning during general anaesthesia significantly decreased the mean arterial pressure (34 +/- 10 mmHg) compared to sedation (4 +/- 2 mmHg, P < 0.01), and vasopressor therapy was required more often. However, CBF remained constant in both anaesthetised (P = 0.83) and sedated patients (P = 0.68) despite beachchair positioning, and the fall in mean arterial pressure in the anaesthetised patients. There was no significant difference in CBF between groups (P = 0.91). These findings indicate that in patients in the beachchair position receiving sevoflurane anaesthesia, CBF is maintained when mean arterial pressure is above 70 mmHg, consistent with intact autoregulation.

Patterns and characteristics of hepatitis C transmission clusters among HIV-positive and HIV-negative individuals in the Australian trial in acute hepatitis C.

BACKGROUND: Injecting drug users remain the population at greatest risk of acquiring hepatitis C virus (HCV) infection, although a recent increase in cases of sexually transmitted HCV infection has been observed among human immunodeficiency virus (HIV)-infected individuals. The extent to which these separate epidemics overlap is unknown. METHODS: The Australian Trial in Acute Hepatitis C (ATAHC) enrolled 163 individuals (29% of whom were HIV infected) with recent HCV infection. E1/HVR1 sequences were used to construct phylogenetic trees demonstrating monophyletic clusters or pairs, and viral epidemic history and phylogeography were assessed using molecular clock analysis. Individual clusters were characterized by clinical and demographic characteristics. RESULTS: Transmission through injection drug use occurred for 73% of subjects, with sexual transmission occurring for 18% (92% of whom were HIV infected). Among 112 individuals with available E1/HVR1 sequences, 23 (20%) were infected with a strain of HCV identical to that of another subject, comprising 4 homologous clusters and 3 monophyletic pairs, the majority of which (78%) were HIV infected. Clusters contained individuals with both injection drug use-related and sex-related acquisition, and in all clusters (except for 1 female HIV-uninfected pair), individuals identified as men who have sex with men, irrespective of HIV status. CONCLUSIONS: This large unique study of HIV-infected and HIV-uninfected individuals with recently acquired HCV infection demonstrates that clustering is common in the HIV-infected population and that it occurred almost invariably among men who have sex with men, irrespective of the actual mode of acquisition. These findings suggest the coexistence of both injection drug use and sexual risk behaviors for individuals in the same social networks and have implications for the development of public health messages. Clinical trial registration. NCT00192569.

Ultrasound of the posterior circumflex humeral artery.

Quadrilateral space syndrome (QSS) is described as compression neuropathy of the axillary neurovascular bundle in the quadrilateral space of the shoulder. This neurovascular bundle includes the posterior circumflex humeral artery (PCHA). Historically, angiography and more recently magnetic resonance angiography have been used to assess occlusion and stenosis of the PCHA in cases of suspected QSS. These traditional imaging techniques have a number of disadvantages in terms of cost, availability, invasiveness and patient comfort. We undertook to examine the ability of ultrasound to reliably visualise the PCHA. Asymptomatic adult volunteers were recruited from staff, and patients attending the radiology department who presented for pathologies unrelated to the shoulder. We used a new technique to assess blood flow in the PCHA, performing the scan from a posterolateral approach on the upper arm just above the level of the surgical neck of the humerus. This technique enabled the scan to be undertaken with the patient seated comfortably. Fifty volunteers were recruited into the study. The mean (+/-SD) age was 35 (+/-14 years). The PCHA was visualised in all patients. Our method was able to maximise Doppler sensitivity and visualisation of the artery without discomfort to the patient in less than 10 min. Ultrasound can be used to reliably visualise the PCHA. Ultrasound has potential to be used in the assessment of the PCHA in cases of QSS.

WAG-F8(m1Ycb) rats harboring a factor VIII gene mutation provide a new animal model for hemophilia A.

BACKGROUND: We recently described an inherited coagulopathy arising in an inbred colony of WAG/RijYcb rats. The bleeding phenotype, demonstrated by both male and female rats, included periarticular hemorrhage, spontaneous bruising, prolonged bleeding from minor wounds and maternal peripartum deaths. Coagulation testing of affected rats revealed normal prothrombin time but prolongation of activated partial thromboplastin time to twice that of controls. OBJECTIVE: To determine the specific coagulation factor and the underlying genetic defect responsible for the inherited coagulopathy in the WAG/RijYcb rats. RESULTS: Evaluation of individual clotting factor activities revealed that the affected animals had a specific deficiency of factor (F) VIII (FVIII). The FVIII gene (F8) has an autosomal location on chromosome 18 in rats, in contrast to its location on the X chromosome in mice and humans. Sequencing of F8 cDNA led to the identification of a point mutation resulting in a substitution, Leu176Pro, in the A1 domain, that is predicted to disrupt the tertiary structure of the FVIII molecule. Administration of human plasma or human recombinant FVIII corrects the coagulation abnormality in the affected animals. CONCLUSIONS: We have now identified the genetic basis of the hemostatic defect in the WAG/RijYcb rat colony. The larger size of rats relative to mice and the presence of this coagulation defect in both sexes provide a unique model, well-suited to the development of novel therapies for acquired and hereditary FVIII deficiencies.

Factors associated with uptake of treatment for recent hepatitis C virus infection in a predominantly injecting drug user cohort: The ATAHC Study.

Despite that the majority of hepatitis C virus (HCV) infection occurs among injection drug users (IDUs), little is known about HCV treatment uptake in this group, particularly during recent infection. We evaluated uptake of treatment for recent HCV infection, including associated factors, within a population predominantly made up of IDUs. The Australian Trial in Acute Hepatitis C was a study of the natural history and treatment of recent HCV infection. All participants with detectable HCV RNA at screening were offered HCV treatment, assessed for eligibility and those initiating treatment were identified. Logistic regression analyses were used to identify predictors of HCV treatment uptake. Between June 2004 and February 2008, 163 were enrolled, with 146 positive for HCV RNA at enrolment. The mean age was 35 years, 77% (n=113) participants had ever injected illicit drugs and 23% (n=34) reported having ever received methadone or buprenorphine treatment. The uptake of HCV treatment was 76% (111 of 146) among those who were eligible on the basis of positive HCV RNA. Estimated duration of HCV infection (OR=1.03 per week, 95% CI=1.00-1.06, P=0.035) and log(10) HCV RNA (OR=1.92 per log(10) increase, 95% CI=1.36-2.73, P<0.001) were independently associated with treatment uptake whereas injection drug use was not. This study demonstrates that a high uptake of HCV treatment can be achieved among participants with recently acquired HCV infection. Decisions about whether to initiate treatment for recently acquired HCV were mainly driven by clinical factors, rather than factors related to sociodemographics or injecting behaviors.

Histone deacetylase inhibitors: Potential in cancer therapy.

The role of histone deacetylases (HDAC) and the potential of these enzymes as therapeutic targets for cancer, neurodegenerative diseases and a number of other disorders is an area of rapidly expanding investigation. There are 18 HDACs in humans. These enzymes are not redundant in function. Eleven of the HDACs are zinc dependent, classified on the basis of homology to yeast HDACs: Class I includes HDACs 1, 2, 3, and 8; Class IIA includes HDACs 4, 5, 7, and 9; Class IIB, HDACs 6 and 10; and Class IV, HDAC 11. Class III HDACs, sirtuins 1-7, have an absolute requirement for NAD(+), are not zinc dependent and generally not inhibited by compounds that inhibit zinc dependent deacetylases. In addition to histones, HDACs have many nonhistone protein substrates which have a role in regulation of gene expression, cell proliferation, cell migration, cell death, and angiogenesis. HDAC inhibitors (HDACi) have been discovered of different chemical structure. HDACi cause accumulation of acetylated forms of proteins which can alter their structure and function. HDACi can induce different phenotypes in various transformed cells, including growth arrest, apoptosis, reactive oxygen species facilitated cell death and mitotic cell death. Normal cells are relatively resistant to HDACi induced cell death. Several HDACi are in various stages of development, including clinical trials as monotherapy and in combination with other anti-cancer drugs and radiation. The first HDACi approved by the FDA for cancer therapy is suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza), approved for treatment of cutaneous T-cell lymphoma.

Quantitative MR imaging evaluation of the cartilage thickness and subchondral bone area in patients with ACL-reconstructions 7 years after surgery.

OBJECTIVE: To evaluate the cartilage thickness (ThC) and subchondral bone area (tAB) of the operated and contra-lateral non-operated (healthy) knees in patients with anterior cruciate ligament (ACL)-reconstruction 7 years after surgery using a quantitative and regional cartilage MR imaging (qMRI) technique. METHODS: Charts of 410 patients with ACL-reconstructions were retrospectively reviewed. Fifty-two patients (male/female, 28/24; mean age, 33.3 years) were included. Patients underwent KT-1000 testing and qMRI of both knees using coronal fat-saturated 3D spoiled gradient-recalled echo (SPGR) sequences (TR/TE, 44/4 ms) at 1.5 T. Quantitative analyses of ThC and tAB in the femoro-tibial cartilage plates were performed using a subregional approach. In addition, qualitative and quantitative assessment of femoral condyle shapes was performed. t tests with Bonferroni corrections were used for statistical analysis of side-to-side differences between the operated and non-operated knees. RESULTS: KT-1000 testing was abnormal in 3/52 patients (6%). Lateral femoral tAB was significantly lower (-9.2%), and medial tibial tAB was significantly larger (+2%) in the operated vs non-operated knee (P<0.001). Regional and subregional ThC side-to-side differences were less than 0.1mm and, except for the external lateral femoral subregion, they were not statistically significant. Flattened and broader shapes of medial femoral condyles (P<0.001) were found in operated knees. No significant association of presence of cartilage or meniscus lesions at surgery with ThC 7 years post-operatively was found (P=0.06-0.98). CONCLUSION: There is evidence for changes in the tAB and femoral shape 7 years post-ACL-reconstruction, but no side-to-side differences in subregional ThC were found between the operated and contra-lateral non-operated knees.