Medication Development For Aud: A Systematic Review Of Clinical Trial Methodology.

Refining clinical trial methodology has become increasingly important as study design is shown to influence treatment efficacy. To maximize the efficiency of randomized clinical trials (RCTs), researchers aim to establish standardized practices. The goal of this systematic review is to describe methodological practices of clinical trials for alcohol use disorder (AUD) over the past 40 years. To achieve this goal, a PubMed search was conducted in April 2023 for RCTs on AUD medications published between July 2018 through April 2023. Resulting studies were combined with a previous search from 1985 through 2018. Inclusion criteria for the RCT studies were: (1) a randomized controlled trial, (2) double or single blinded, (3) placebo or active control condition, (4) alcohol use as the primary endpoint, (5) 4 or more weeks of treatment, and (6) 12 or more weeks of follow-up. In total, methodological data from 139 RCTs representing 19 medications and spanning the past four decades were summarized. Results indicated that the most common medications tested were naltrexone (k=42), acamprosate (k=24), and baclofen (k=11). On average, participants were 74% male and consumed 226 drinks per month pre-randomization. The median length of treatment was 12 weeks (IQR= 12-16; min=4 max=52) and the median follow-up duration was 12.5 weeks (IQR: 12-26; min=7 max= 104). There were two broad domains of outcomes (i.e., abstinence and heavy drinking), with most studies featuring outcomes from both domains (k=87; 63%). Reporting practices were summarized by decade, revealing an increased enrollment of females, better reporting of race and ethnicity data, and less studies requiring pre-trial abstinence. This review summarizes the current state of the literature on randomized clinical trials for AUD including effect sizes for individual studies and summaries of key methodological features across this representative set of clinical trials.

Multiscale X-ray phase-contrast tomography: From breast CT to micro-CT for virtual histology.

Phase-contrast imaging techniques address the issue of poor soft-tissue contrast encountered in traditional X-ray imaging. This can be accomplished with the propagation-based phase-contrast technique by employing a coherent photon beam, which is available at synchrotron facilities, as well as long sample-to-detector distances. This study demonstrates the optimization of propagation-based phase-contrast computed tomography (CT) techniques for multiscale X-ray imaging of the breast at the Elettra synchrotron facility (Trieste, Italy). Two whole breast mastectomy samples were acquired with propagation-based breast-CT using a monochromatic synchrotron beam at a pixel size of 60 µm. Paraffin-embedded blocks sampled from the same tissues were scanned with propagation-based micro-CT imaging using a polychromatic synchrotron beam at a pixel size of 4 µm. Images of both methodologies and of the same sample were spatially registered. The resulting images showed the transition from whole breast imaging with propagation-based breast-CT methodology to virtual histology with propagation-based micro-CT imaging of the same sample. Additionally, conventional histological images were matched to virtual histology images. Phase-contrast images offer a high resolution with low noise, which allows for a highly precise match between virtual and conventional histology. Furthermore, those techniques allow a clear discernment of breast structures, lesions, and microcalcifications, being a promising clinically-compatible tool for breast imaging in a multiscale approach, to either assist in the detection of cancer in full volume breast samples or to complement structure identification in paraffin-embedded breast tissue samples.

Splinting Open Tray Impression Copings Using Long Shank Carbide Burs during Definitive Impression: A Dental Technique.

AIM: To splint implant impression copings using long shank carbide burs for definitive implant impressions. BACKGROUND: The accurate transfer of the orientation recorded by impression copings to a definitive cast is a challenging step in implant prosthodontics. For achieving a passive fit from the mouth to the cast may include some discrepancies. Traditional methods of splinting can be time-consuming and troublesome to handle. TECHNIQUE: This article describes a technique by using long shank carbide burs for splinting implant impression copings. CONCLUSION: The favored implant splinting, evidence was inconclusive, and the data supporting splint pickup was the better performing technique, especially with an increased number of implants. CLINICAL SIGNIFICANCE: This technique causes minimal discomfort and is straightforward when compared to other techniques.

Optimization of a customized simultaneous algebraic reconstruction technique algorithm for phase-contrast breast computed tomography.

Objective.To introduce the optimization of a customized GPU-based simultaneous algebraic reconstruction technique (cSART) in the field of phase-contrast breast computed tomography (bCT). The presented algorithm features a 3D bilateral regularization filter that can be tuned to yield optimal performance for clinical image visualization and tissues segmentation.Approach.Acquisitions of a dedicated test object and a breast specimen were performed at Elettra, the Italian synchrotron radiation (SR) facility (Trieste, Italy) using a large area CdTe single-photon counting detector. Tomographic images were obtained at 5 mGy of mean glandular dose, with a 32 keV monochromatic x-ray beam in the free-space propagation mode. Three independent algorithms parameters were optimized by using contrast-to-noise ratio (CNR), spatial resolution, and noise texture metrics. The results obtained with the cSART algorithm were compared with conventional SART and filtered back projection (FBP) reconstructions. Image segmentation was performed both with gray scale-based and supervised machine-learning approaches.Main results.Compared to conventional FBP reconstructions, results indicate that the proposed algorithm can yield images with a higher CNR (by 35% or more), retaining a high spatial resolution while preserving their textural properties. Alternatively, at the cost of an increased image 'patchiness', the cSART can be tuned to achieve a high-quality tissue segmentation, suggesting the possibility of performing an accurate glandularity estimation potentially of use in the realization of realistic 3D breast models starting from low radiation dose images.Significance.The study indicates that dedicated iterative reconstruction techniques could provide significant advantages in phase-contrast bCT imaging. The proposed algorithm offers great flexibility in terms of image reconstruction optimization, either toward diagnostic evaluation or image segmentation.

Growth hormone deficiency and other endocrinopathies after childhood brain tumors: results from a close follow-up in a cohort of 242 patients.

PURPOSE: Brain tumors are the most common solid tumor in children. The prevalence of survivors from these cancers has been increasing, presenting endocrine sequelae in more than 40% of the cases. Our aim was to characterize the endocrinopathies diagnosed in this population, exploring the outcomes of growth hormone treatment. METHODS: We have performed a retrospective analysis of the survivors that were followed-up through a close protocol at our endocrine late-effects clinic. RESULTS: 242 survivors, followed during 6.4 (0-23.4) years, were considered. The median age at tumor diagnosis was 6.7 (0-18) years and pilocytic astrocytoma was the most frequent neoplasm (33.5%). The prevalence of endocrinopathies was of 71.5%, with growth hormone deficiency being the most frequent (52.9%). An indirect correlation between the age at the beginning of somatropin and growth velocity in the first year of treatment was observed. Those treated with craniospinal radiotherapy presented a smaller final upper/lower segments ratio comparing with those that only received cranial radiotherapy. However, their final height was not compromised when compared to their family height target. We found pubertal delay in 12%; accelerated/precocious puberty in 13.2%; central and primary hypogonadism in 21.9% and 3.3%, respectively; primary and central hypothyroidism in 23.6% and 14.5%, respectively; thyroid nodules in 7.4%; ACTH deficiency in 10.3% and diabetes insipidus in 12%. CONCLUSION: This study reveals a higher prevalence of endocrinopathies in brain tumors survivors and explores the influence of craniospinal irradiation in the adult body proportions. It reinforces the importance of routine follow-up among survivors.

All-inside repair of meniscal bucket handle tears: a retrospective study at mean 4-years follow-up evaluation.

Bucket-handle tears represent approximately 10% of all meniscal tears. Despite the common treatment is subtotal meniscectomy, repair is technically feasible although complex, and represents a key strategy to avoid severe meniscal tissue loss that could accelerate joint degeneration over time. The aim of this retrospective study was to determine the outcomes of arthroscopically-assisted bucket-handle tear repair, and to identify factors correlating with clinical results. Fifty-four patients affected by meniscal bucket handle tear were included in the present retrospective analysis and evaluated up to mean 4-years follow-up. All patients were treated by arthroscopic-assisted all-inside repair. The primary outcome was considered the need for a re-operation due to failure of meniscal repair. Patients were also evaluated by the following items: KOOS, Lysholm, Tegner, IKDC-subjective and Quadruple-VAS score. Subgroup analysis was performed to identify whether concurrent ACL reconstruction, side of the lesion, age at surgery and time from injury to repair could influence clinical outcome. Ten out 54 patients (18.5%) were considered failed and needed reoperation, mainly within one year from surgery. Overall, there was a significant increase in all clinical scores considered and patients were able to get back to previous sport activity level. Patients with concurrent ACL reconstruction presented a lower risk of failure (p=0.025). Patients with lateral meniscus repair showed better clinical outcome compared to medial meniscus. Timing from injury and age at surgery did not correlated with clinical outcome. Our series showed fair results in bucket handle repair up to middle term evaluation. Concomitant ACL reconstruction was associated with lower failure rate whereas lateral meniscus involvement was associated with higher functional scores at final follow-up evaluation.

Incidental finding of adenocarcinoma in a gallbladder lumen with no wall involvement.

Gallbladder cancer (GBC) is a rare disease characterized by its aggressiveness. Resection with free tumour margins is the sole curative treatment and, in incidental findings, surgical reapproach is recommended for segmentectomy IVb and V or wedge resection of the gallbladder fossa and lymphadenectomy. Here we report a case of gallbladder adenocarcinoma as an incidental finding in a fragment in its lumen with no wall involvement evidentiated. The patient was reoperated for resection of the gallbladder bed with hepatic hilum and cystic duct lymphadenectomy, later evidentiated as free of residual disease. The normality of the bile ducts evidenced by imaging studies, in addition to signs of chronic cholecystitis corroborate to GBC diagnosis. We suspect that the fragment was detached gallbladder polypoid neoplastic lesion. Despite the lack of clinical manifestations, the fast surgical interventions and the histopathological analysis of the material was probably a prognostic determinant for the patient.

First 3D imaging characterization of Pele's hair from Kilauea volcano (Hawaii).

In this work the morphologic features of Pele's hair formed during three different eruptions of Kilauea volcano have been investigated: fountaining from Kilauea Iki's 1959 Episode 1, weak explosive activity from Halemaumau lava lake and littoral explosions at Waikupanaha (2009). Morphological studies were performed by optical, stereo- and scanning electron microscopy. For the first time 3D image analysis was carried out by synchrotron radiation X-ray computed microtomography, which allowed a high-resolution 3D reconstruction of the internal structure of each Pele's hair, highlighting several differences in terms of number density, elongation and shape of the vesicles between the samples from the three eruptions. We identified three main parameters determining these differences: initial size of the magma droplet, ejection velocity and magma viscosity. Pele's hair erupted during the Kilauea Iki's fountaining shows the highest thickness and the least elongated shape of the vesicles, though it is related to fast ejection of a low viscosity magma. We therefore suggest that the size of magma droplets is the main parameter influencing the morphology and inner textures of the Pele's hair. The comparison with Pele's hair of similar eruptions elsewhere demonstrates that there is no univocal correspondence between eruptive style and Pele's hair texture.

Autologous micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis: an update at 3 year follow-up.

BACKGROUND: Conservative therapies for the treatment of knee degenerative processes are used before resorting to surgery; nonetheless, they may offer only short-term benefits. Encouraging preliminary results have been reported using mesenchymal stem cells (MSCs), either alone or in association with surgery. Among the many sources, adipose tissue has created a huge interest, because of its anti-inflammatory and regenerative properties ascribed to the cells of its stromal vascular fraction. We previously reported the safety and feasibility of autologous micro-fragmented adipose tissue as adjuvant for the surgical treatment of diffuse degenerative chondral lesions at 1 year. Here we present the outcomes of the same cohort of patients evaluated at 3 year follow-up. Micro-fragmented adipose tissue was obtained using a minimal manipulation technique in a closed system. The safety of the procedure was evaluated by recording type and incidence of any adverse event. The clinical outcomes were determined using the KOOS, IKDC-subjective, Tegner Lysholm Knee, and VAS pain scales taken pre-operatively and at 12 and 36 months follow-up. FINDINGS: No adverse events, lipodystrophy cases at the harvesting site nor atypical inflammatory reactions at the joint level were reported. Of the 30 patients previously treated, one was lost, and seven received additional treatments in the period of observation. On average, the 22 patients that had no other treatments in the 3-year period showed that the results observed at 1 year were maintained. Moreover, 41, 55, 55 and 64% of the patients improved with respect to the 1-year follow-up in the Tegner Lysholm Knee, VAS, IKDC-subjective and total KOOS, respectively. CONCLUSION: Our results point to autologous and micro-fragmented adipose tissue injection as an innovative and safe approach for the management of diffuse degenerative knee chondropathy in the mid-term. The procedure is simple, affordable, minimally invasive, and compliant with the regulatory panorama.

Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO.

Background: Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial. Patients and methods: Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR < 3) versus high (NLR ≥ 3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution. Results: NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS) [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the multivariable model, NLR retained a significant association with OS [HR 1.44 (95% CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P = 0.375]. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI 0.59-1.12) for high NLR]. Conclusion: This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.

Knee Septic Arthritis after Arthroscopy: Incidence, Risk Factors, Functional Outcome, and Infection Eradication Rate.

Purpose Septic knee arthritis following arthroscopy is a rare but dreaded complication. Definition and management of knee deep infections are quite discussed in literature. In this review, literature regarding infections after knee arthroscopy is analyzed highlighting the incidence, causative bacteria, risk factors as well as clinical outcomes. Methods We performed a review of the literature matching the following key words: "septic arthritis" OR "infection" AND "arthroscopy" AND "knee." Knee arthroscopic procedures, such as debridement, meniscectomy, meniscus repair, synovectomy, microfracture, and lateral release, were considered. Complex procedures, such as ligament reconstruction, fractures, or complex cartilage repair techniques, were not included. Results Thirteen studies were included in this review. Incidence of infection ranged from 0.009 to 1.1% in patients undergoing simple arthroscopic procedures. Staphylococci are the most commonly isolated organisms from postarthroscopy infection. Use of intraoperative intra-articular steroids, smoking, obesity, male sex, diabetes, number of procedures performed during surgery, time of surgery, and tourniquet time of more than 60 minutes have been certified as risk factors for knee infection. Conclusion Postarthroscopy septic arthritis of the knee causes significant morbidity, usually requiring readmission to the hospital, at least one additional operation, and prolonged antibiotic therapy, both intravenous and oral. Prompt diagnosis and treatment are associated with a high success rate. Level of Evidence Level IV, systematic review of I-IV studies.

Heat shock induces the expression of pro-inflammatory cytokines in human Achilles tendon tenocytes.

The aim of our study is to investigate the behaviour of healthy and tendinopathic human tenocytes after a heat shock. After we harvested tendinopathic and healthy human tendon samples, we split tenocytes into 4 groups: 3 groups were submitted to heat shock, followed by different periods of post-heating (2, 4 and 20 h). The other group represents our negative control. The target genes were analysed using Real Time PCR. IL-1ß and IL-6 expression were significantly increased in tendinopathic samples after heat shock. COL1 and COL3 expression were increased in non-stimulated tendinopathic tenocytes, but their levels significantly decreased after heat shock (p less than 0.01). COL3 levels increase in healthy samples after 20 h post-heating (p less than 0.01). COL1 and COL3 decreased after heat shock as a sign of the failure of repair mechanisms in tendinopathic tendons. Heat shock in in vitro models was insufficient to trigger pro-inflammatory cytokines in healthy human tenocytes.

Surgical treatment of sacral chordoma: survival and prognostic factors.

INTRODUCTION: Sacral chordoma is a rare low-to-intermediate grade malignant tumour. The mainstay of treatment is still surgery with en bloc and wide resection margins, which can grant the best chances of a long-term control or cure of this disease. The first aim of this paper is to collect data about survival, time to local recurrence and metastasis among patients affected by sacral chordoma and primarily treated with surgery. The second aim is to analyze the influence of level resection, tumor volume and surgical margins on local recurrence. MATERIALS AND METHODS: The study population was composed of 14 patients treated with sacral chordoma resection at the National Tumour Institute of Naples-Pascale (Italy) from January 2000 to June 2013. The median follow-up was 84 months (range 24-132 months). The follow-up was characterized by: standard radiographs, MRI, and a CT scan of the chest annually. Time to recurrence or metastasis was calculated from the date of resection to the date of diagnosis of first recurrence or metastasis. RESULTS: Out of all the patients, six died (42.86 %) during the follow-up; 6 (42.86 %) had local recurrence; 4 (28.57 %) had metastasis. At univariate analysis wide surgical margins (R0) were associated with increased survival up to a local recurrence (OR = 0.0286; 95 % CI = 0.0014-0.5739; P = 0.026); the level of resection (OR = 3.33; 95 % CI = 0.3619-30.7025; P = 0.592) and tumour volume (P = 1) did not show a statistically significant correlation. DISCUSSION: Based on our experience, we hope all patients to be treated by surgery, the only good standard treatment of this disease. The resection should result in margins as wide as possible. For these reasons, it is essential for this disease to be treated in highly specialized centres because only a complete surgery can offer a chance to care for these patients. CONCLUSIONS: Solid survival at long-term follow-up can be achieved by a surgical resection performed with wide margins.

Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest.

BACKGROUND: Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line trials of chemotherapy ± anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). These associations and the predictive accuracy of response measurements for survival parameters were investigated in the phase III TRIBE trial of FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev. PATIENTS AND METHODS: A landmark approach was adopted to define the assessable population. The distribution of RECIST response rate, ETS and DoR was compared in the two arms. Associations between response measurements and progression-free survival (PFS), post-progression survival (PPS) and OS were tested by univariate and multivariate Cox models. Prediction performance of each factor was estimated by C-index. RESULTS: A significantly higher percentage of patients in the FOLFOXIRI plus bev arm achieved ETS ≥20%, when compared with the control arm (62.7% versus 51.9%, P = 0.025). Also the DoR was significantly higher in the triplet plus bev arm (43.4% versus 37.8%, P = 0.003). Both ETS and DoR were associated with PFS, PPS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. Both ETS and DoR were able to predict survival as accurately as RECIST response. CONCLUSION: FOLFOXIRI plus bev improves ETS and DoR when compared with FOLFIRI plus bev. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus bev. ETS is a promising and valuable end point for clinical trials' design deserving further investigation.

Whole-body vibration improves functional capacity and quality of life in patients with severe chronic obstructive pulmonary disease (COPD): a pilot study.

BACKGROUND: Exercise intolerance is a common development in patients with chronic obstructive pulmonary disease (COPD). There is little data on the use of an isolated program using vibration platform training on functional capacity in these patients, which is an area that deserves investigation. AIM: To investigate the effect of training on a vibrating platform (whole-body vibration [WBV]) on functional performance and quality of life of subjects with COPD. METHODS: A randomized controlled crossover pilot study with eleven subjects with COPD (forced expiratory volume in 1 second [FEV1]% predicted =14.63±11.14; forced vital capacity [FVC]% predicted =48.84±15.21; FEV1/FVC =47.39±11.63) underwent a 12-week WBV training program. Participants were randomized into the intervention group (IG) undergoing three sessions per week for a total of 12 weeks and control group (CG) without intervention. We evaluated the 6-minute walk test (6MWT), distance walked (DW), duration of the walk (TW), and index of perceived exertion (IPE), quality of life using St George's Respiratory Questionnaire (SGRQ) and developed a 12-week program of training on a vibrating platform. RESULTS: The mean age was 62.91±8.82 years old (72.7% male). The DW increased at the end of training with a difference between groups of 75 m; all domains of the SGRQ improved at the end of training. The effect size Cohen's d ranged from small to large for all the measured results. CONCLUSION: These preliminary results suggest that WBV may potentially be a safe and feasible way to improve functional capacity in the 6MWT of patients with COPD undergoing a training program on the vibrating platform as well as in all domains of the SGRQ quality of life. However, further studies with a larger number of patients are needed to establish the long-term effect on functional capacity and quality of life in these patients.

Influence of posture on the ventilatory pattern and the thoraco-abdominal kinematics of patients with chronic obstructive pulmonary disease (COPD).

OBJECTIVE: Evaluate the influence of posture on ventilatory pattern, compartmental distribution of volume of chest wall and thoraco-abdominal kinematics of patients with severe chronic obstructive pulmonary disease (COPD). DESIGN: Cross-sectional study. METHODS: Twelve, male patients with severe COPD (Forced Expiratory Volume in the first second (FEV1) = 24.35 ± 4.52%, Forced Vital Capacity% (FVC%) = 60 ± 13.39% and relationship FEV1/FVC = 53.42 ± 14.47). The distribution of the volume of the ribcage [pulmonary rib cage (Rcp), abdominal ribcage (Rca) and abdomen (Ab)] during quiet breathing in a sitting position without back support (SWB), sitting with backrest (SB) and supine position (SUP) was determined using an opto-electronic plethysmograph. RESULTS: The following differences were observed: a greater tidal volume in the SWB position when compared to the SB position (p = 0.01); greater expiratory time in the SUP position in relation to the SWB (p = 0.03) and SB (p = 0.01); and increased abdominal contribution to the tidal volume in the SUP position in relation to the SWB (p < 0.01) and SB (p < 0.001). No difference was found in the thoraco-abdominal synchrony among the positions. CONCLUSION: Sitting position without back support enhances the activation of respiratory muscles by increasing the tidal volume and supine position seems to favor lung deflation by increasing the expiratory time. It seems appropriate to adopt these positions to optimize the ventilation/perfusion relationship and physiotherapeutic intervention in different clinical conditions.

Factors associated with the need for blood transfusion during hysterectomy.

OBJECTIVE: To identify the preoperative clinical conditions associated with the need to perform a blood transfusion among patients undergoing hysterectomy. METHODS: In a retrospective, comparative, case-control trial at the University Hospital, Nuevo León, Mexico, the records of patients who underwent elective hysterectomy between 2007 and 2009 were reviewed. Patients were grouped depending on whether or not they required blood transfusion. Clinical features were compared and statistical analysis was performed via the χ(2) test. RESULTS: Among 794 patients who underwent hysterectomy, 89 (11.2%) required transfusion. The factors significantly associated with transfusion were history of abnormal uterine bleeding (67.0% versus 52.1%), preoperative hemoglobin level (10.1g/dL versus 12.3g/dL), magnitude of intra-operative bleeding (410 mL versus 298 mL), and operative time (172 min versus 144 min); P<0.001. A significant number of patients who underwent transfusion had increased preoperative prothrombin levels; P=0.04. CONCLUSION: Hemoglobin level before surgery and a history of abnormal uterine bleeding can be identified preoperatively and might warn about the possibility of a need for transfusion among patients undergoing hysterectomy. For young patients, alterations in clotting mechanisms should be ruled out.

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion.

OBJECTIVE: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. METHODS: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. RESULTS: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. CONCLUSIONS: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors.

Oxidative stress, inflammation, and muscle soreness in an 894-km relay trail run.

We describe the effects of multi-day relay trail running on muscle soreness and damage, and systemic immune, inflammatory, and oxidative responses. 16 male and 4 female athletes ran 894 km in 47 stages over 95 h, with mean (SD) 6.4 (1.0) stages per athlete and 19.0 (1.7) km per stage. We observed post-pre run increases in serum creatine kinase (qualified effect size extremely large, p = 0.002), IL-6 (extremely large, p < 0.001), urinary 8-isoprostane/creatinine (extremely large, p = 0.04), TNF-α (large, p = 0.002), leukocyte count (very large, p < 0.0001) and neutrophil fraction (very large, p < 0.001); and reductions in hemoglobin (moderate, p < 0.001), hematocrit (moderate, p < 0.001), and lymphocyte fraction (trivial, p < 0.001). An increase in ORAC total antioxidant capacity (TAC, small, p = 0.3) and decrease in urinary 8-OHdG/creatinine (small, p = 0.1) were not statistically significant. During the run, muscle soreness was most frequent in the quadriceps. The threshold for muscle pain (pain-pressure algometry) in the vastus lateralis and gastrocnemius was lower post-run (small, p = 0.04 and 0.03). Average running speed was correlated with algometer pain and leukocyte count (large, r = 0.52), and TAC was correlated with IL-6 (very large, r = 0.76) and 8-isoprostane/creatinine (very large, r = -0.72). Multi-day stage-racing increases inflammation, lipid peroxidation, muscle damage and soreness without oxidative DNA damage. High TAC is associated with reduced exercise-induced lipid peroxidation, but is not related to immune response or muscle damage.