Melanogenic effect of dersimelagon (MT-7117), a novel oral melanocortin 1 receptor agonist.

Background: The activation of melanocortin 1 receptor (MC1R) on melanocytes stimulates the production of eumelanin. A tridecapeptide α melanocyte-stimulating hormone (αMSH) is known to induce skin pigmentation. Objectives: We characterised the properties of a novel oral MC1R agonist dersimelagon (MT-7117) with respect to its specific binding to MC1R, downstream signalling and eumelanin production in experimental models. Methods: The competitive binding and production of intracellular cyclic adenosine 3', 5'-monophosphate in cells expressing recombinant melanocortin receptors were examined. A mouse melanoma cell line B16F1 was used for the evaluation of in vitro melanin production. The in vitro activity of MT-7117 was determined with αMSH and [Nle4, D-Phe7]-αMSH (NDP-αMSH) as reference comparators. The change of coat colour and skin pigmentation were evaluated after repeat administration of MT-7117 by oral gavage to C57BL/6J-Ay/+ mice and cynomolgus monkeys, respectively. Results: MT-7117 showed the highest affinity for human MC1R compared to the other melanocortin receptors evaluated and agonistic activity for human, cynomolgus monkey and mouse MC1R, with EC50 values in the nanomolar range. In B16F1 cells, MT-7117 increased melanin production in a concentration-dependent manner. In vivo, MT-7117 (≥0.3 mg/kg/day p.o.) significantly induced coat colour darkening in mice. MT-7117 (≥1 mg/kg/day p.o.) induced significant skin pigmentation in monkeys and complete reversibility was observed after cessation of its administration. Conclusions: MT-7117 is a novel oral MC1R agonist that induces melanogenesis in vitro and in vivo, suggesting its potential application for the prevention of phototoxic reactions in patients with photodermatoses, such as erythropoietic protoporphyria and X-linked protoporphyria.

Association between BIA-derived Phase Angle and Sarcopenia and Improvement in Activities of Daily Living and Dysphagia in Patients undergoing Post-Stroke Rehabilitation.

OBJECTIVES: To investigate the predictive value of the BIA-derived phase angle with respect to the functional prognosis and baseline sarcopenia in patients undergoing post-stroke rehabilitation. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Overall, 577 Japanese patients admitted to a post-acute care hospital from 2016 to 2020 were recruited. MEASUREMENTS: Body composition analysis, which included BIA-derived phase angle and skeletal muscle mass, was performed using bioelectrical impedance analysis (BIA). Study outcomes included physical function assessed using the Functional Independence Measure (FIM-motor) and the level of dysphagia assessed using the Food Intake LEVEL Scale (FILS). Sarcopenia was defined as the loss of skeletal muscle mass and decreased muscle strength. Receiver operating characteristic curves were used to calculate the optimal cutoff value of BIA-derived phase angle to diagnose sarcopenia. Multivariate analyses were used to determine whether the BIA-derived phase angle at admission was associated with outcomes at discharge and baseline sarcopenia. RESULTS: After enrollment, 499 patients (mean age: 74.0 ± 13.1 years; 52.0% men) were examined. The median FIM-motor and FILS scores at admission were 47 (20-69) and 8 (7-10), respectively. Sarcopenia was observed in 43.2% of patients. After adjusting for potential confounders, BIA-derived phase angle was positively associated with FIM-motor scores at discharge (ß = 0.134, P < 0.001), FIM-motor score gain (ß = 2.504, P < 0.001), and FILS scores at discharge (ß = 0.120, P = 0.039). BIA-derived phase angle was negatively associated with the sarcopenia diagnosis at baseline (odds ratio = -0.409, P < 0.001); its cutoff value was 4.76° (sensitivity 0.800, specificity 0.790, P < 0.001) for sarcopenia diagnosis in men and 4.11° (sensitivity 0.735, specificity 0.829, P < 0.001) in women. CONCLUSION: BIA-derived phase angle was positively associated with the recovery of physical function and dysphagia level and negatively associated with baseline sarcopenia in patients undergoing post-stroke rehabilitation. The BIA-derived phase angle cutoff for sarcopenia diagnosis was 4.76° for men and 4.11° for women.

Five-year point prevalence survey of healthcare-associated infections and antimicrobial use in a Japanese university hospital.

BACKGROUND: Periodic point prevalence surveys (PPSs) provide a method for assessing changes in healthcare-associated infections (HAIs) and antimicrobial use over time. Following the introduction of an antimicrobial stewardship programme at Nagoya University Hospital (Aichi, Japan) a five-year PPS study was performed to highlight any epidemiological changes. METHODS: One-day PPSs were performed annually in July at Nagoya University Hospital. Data on patient characteristics, medical devices, active HAIs and antimicrobial use were collected using a standard data-collection form. RESULTS: A total of 4339 patients were included. Over the five-year study period the median patient age was 62 years, median duration of hospital admission was nine days, 9% of patients had an HAI and 35.2% received at least one antimicrobial. Overall there were 406 HAIs (95% confidence interval, 369-447) with surgical site infection, pneumonia and febrile neutropenia occurring most frequently. Enterobacterales were the most common pathogens (N = 78, 28.6%) and 32.1% were third-generation cephalosporin-resistant. Meropenem was the most frequently prescribed antimicrobial for HAIs. Surgical antimicrobial prophylaxis changed drastically, with shorter durations and a marked reduction in oral cephalosporin use. However, antimicrobials for medical prophylaxis gradually increased. CONCLUSIONS: This five-year PPS study shows consistent data for patient background, HAIs and causative pathogens and highlights changes in antimicrobial use during the era of the National Action Plan on Antimicrobial Resistance. To describe the epidemiology of Japanese hospitals by PPS, multicentre PPSs including in community hospitals should be performed annually.

Laparoscopic and open surgery in patients with transverse colon cancer: short-term and oncological outcomes.

BACKGROUND: Studies evaluating the outcomes after laparoscopic resections of transverse colon cancers are scant. This manuscript aimed to compare surgical and oncological outcomes after laparoscopic (Lap) and open procedures for transverse colon carcinomas. METHODS: All consecutive patients who underwent resection for a cancer located in the transverse colon between 2003 and 2019 were reviewed. Patients were categorized according to the surgical approach (Lap versus open) and groups were compared. Outcome measures were the short-term results, complications and functional recovery; moreover, recurrence-free survival (RFS) and overall survival (OS) rates were compared overall and after propensity score matching (PSM) based on age, sex, ASA classification, BMI, carcinoembryonic antigen (CEA) level, use of postoperative chemotherapy, location of tumour, stage and grading, operation time, blood loss and complications. RESULTS: Of 248 transverse resections reviewed, 146 (81 Lap and 65 open) were selected for data analysis. Blood loss, fluid intake and the incidence of wound infection were significantly lower and the hospital stay was significantly shorter in the Lap group (P < 0.001). The operation time and incidence of complications (Clavien-Dindo classification grade 3 or above) did not differ significantly between the two groups. Mean follow-up was of 75.4 months in the Lap group and 78.6 months in the open group. Regression analyses showed that OS was associated with the postoperative carcinoembryonic antigen (CEA) level (hazard ratio 1.18 (95 per cent c.i. 1.10 to 1.27); P < 0.001), BMI (hazard ratio 0.81 (95 per cent c.i. 0.68 to 0.96); P = 0.017), operation time (hazard ratio 0.99 (95 per cent c.i. 0.97 to 1.00; P = 0.010), and postoperative chemotherapy (hazard ratio 0.27 (95 per cent c.i. 0.08 to 0.96); P = 0.042), while RFS was associated with the postoperative CEA level (hazard ratio 1.13 (95 per cent c.i. 1.07 to 1.20); P < 0.001). PSM selected 42 patients for data comparison of long-term results, and showed no significant differences between groups (RFS: P = 0.530; OS: P = 0.561). CONCLUSION: Lap and open resections for transverse colon cancer provided similar outcomes in terms of severe post-operative complication and long-term results.

Bifidobacterium Breve A1 Supplementation Improved Cognitive Decline in Older Adults with Mild Cognitive Impairment: An Open-Label, Single-Arm Study.

OBJECTIVES: We previously reported the therapeutic potential of Bifidobacterium breve A1 (B. breve A1) for preventing cognitive impairment in Alzheimer's disease model mice, which suggested that supplementation of the probiotics could be an effective therapeutic strategy for managing cognitive function in mild cognitive impairment (MCI). DESIGN AND SETTINGS: We conducted an open-label, single-arm study to examine the effects of 24-week supplementation of B. breve A1 on elderly with MCI in Aki Orthopedics Rehabilitation Clinic in Japan. PARTICIPANTS: 27 participants were screened by their Mini Mental State Examination (MMSE) scores. MEASUREMENTS: Cognitive function was assessed using MMSE and Digit Symbol Substitution Test (DSST) at baseline and every 8 weeks. Mental condition and quality of life for gastrointestinal symptoms were measured using the Profile of Mood States 2nd Edition (POMS2), and the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: Of the 27 participants enrolled, 19 completed the study. MMSE scores were significantly increased during the intervention by mixed model Dunnett's test and Wilcoxon signed-rank tests (+1.7, P < 0.01). POMS2 and GSRS scores were significantly improved during intervention when analyzed by Wilcoxon signed-rank tests. CONCLUSION: The present study showed that oral supplementation of B. breve A1 in participants with MCI improved cognitive function, thus suggesting the potential of B. breve A1 for improving cognitive function and maintaining quality of life of the elderly. Further randomized, double-blind placebo-controlled studies are worth conducting to examine the beneficial effect of B. breve A1.

Heterocyclic boronic acids display sialic acid selective binding in a hypoxic tumor relevant acidic environment.

Boronic acids are well known for their ability to reversibly interact with the diol groups found in sugars and glycoproteins. However, they are generally indiscriminate in their binding. Herein we describe the discovery of a group of heterocyclic boronic acids demonstrating unusually high affinity and selectivity for sialic acids (SAs or N-acetylneuraminic acid), which are sugar residues that are intimately linked with tumor growth and cancer progression. Remarkably, these interactions strengthen under the weakly acidic pH conditions associated with a hypoxic tumoral microenvironment. In vitro competitive binding assays uncovered a significantly higher ability of 5-boronopicolinic acid, one of the derivatives identified in this work as a strong SA-binder, to interact with cell surface SA in comparison to a gold-standard structure, 3-propionamidophenylboronic acid, which has proven to be an efficient SA-binder in numerous reports. This structure also proved to be suitable for further chemical conjugation with a well-preserved SA-binding capability. These findings suggest an attractive alternative to other ongoing boronic acid based chemistry techniques aiming to achieve tumor-specific chemotherapies and diagnoses.

Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women.

Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation. SUMMARY: Background Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 µg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

Streptozotocin induces neurite outgrowth via PI3K-Akt and glycogen synthase kinase 3ß in Neuro2a cells.

Streptozotocin (STZ), a naturally occurring chemical, is toxic to the various kinds of cells such as insulin-producing beta cells. However, the beneficial effect of STZ on neuronal cells such as neurite outgrowth-inducing activity has been unknown. In this study, we examined the effect of STZ on neurite outgrowth in mouse neuronal Neuro2a cells. STZ (0.01 mM~5 mM) exerted remarkable neurite outgrowth-inducing activity in Neuro2a cells in a concentration dependent manner. STZ also had the same neurite outgrowth-inducing activity as that of retinoic acid (RA), which is well known neurite outgrowth inducer. As with the result of RA treatment, STZ administration increased MAP2-positive cells. The MAP2-positive cells reflect neurite outgrowth-induced cells. STZ (0.01 mM~5 mM) did not induce cell death, but significantly decreased cell proliferation. The serine/threonine kinase Akt, a downstream target of phosphatidylinositol-3 kinase (PI3K), was transiently phosphorylated at Ser473 and at Thr303 by STZ (5 mM) administration. Glycogen synthase kinase 3ß (GSK3ß), which has been reported to be inactivated by Akt, was also transiently phosphorylated at Ser9 by STZ (5 mM) administration. In addition, a blocker of PI3K, LY294002 (10 µM), significantly attenuated STZ-induced neurite outgrowth. These results suggest that STZ induces neurite outgrowth via activation of PI3K-Akt signaling pathway and GSK3ß inhibition.

Comparison of oncological safety between nipple sparing mastectomy and total mastectomy using propensity score matching.

INTRODCUTION: Although nipple sparing mastectomy (NSM) has attracted increased recognition as an alternative to traditional mastectomy approaches, its oncological safety is unclear. The purpose of this study was to compare the local recurrence rate between NSM and total mastectomy (TM). METHODS: Between 2003 and 2013, 121 and 557 patients with stage 0-III breast cancer underwent NSM and TM respectively. Multivariate Cox regression and propensity score models were used to compare the two groups. RESULTS: There was no significant difference in the five-year local recurrence rate between the NSM and TM groups (7.6% vs 4.9%, p=0.398). In multivariate analysis, NSM was not a risk factor for local recurrence (hazard ratio: 1.653, 95% confidence interval: 0.586-4.663, p=0.343). Propensity score matching found similar five-year local recurrence free survival rates between the two groups (92.3% vs 93.7%, p=0.655). CONCLUSIONS: Our results suggest that NSM may provide oncological safety comparable with mastectomy for carefully selected patients.

Recent trends in testosterone testing, low testosterone levels, and testosterone treatment among Veterans.

Low serum testosterone (T) is common and increasingly prevalent with increased age. Recent studies report an 'epidemic' of T prescribing and concern about unnecessary T treatment. We investigated the number of men tested for T, the prevalence of low serum T levels, and initiation of T treatment among those with low T levels in men treated at Veterans Affairs (VA) facilities in the Northwest US (VISN 20). We identified male Veterans aged 40-89 years and examined yearly proportions of men tested for T, found to have low T levels (total T < 280 ng/dL, free T < 34 pg/mL, or bioavailable T < 84 ng/dL), and subsequently treated with T from 2002 to 2011. We excluded men who had T treatment in the year prior and men with diagnoses of prostate or breast cancer. Treatment initiation was defined as the first prescription for T within a year following a low T test. From 2002 to 2011, the yearly population of eligible men in VISN 20 increased from 129 247 to 163 572. The proportion of men who had serum T tests increased from 3.2% in 2002 to 5.8% in 2011. Among the tested men, the percentage of men with low T levels increased from 35.0 to 47.3%. However, the proportion of men with low T levels who were given T treatment within a year decreased from 31.0 to 28.0%. Despite large increases in T testing, and detection of men with low T levels, there was a slight decrease in the proportion of men with low T levels who were treated with T. The decrease in T treatment during this time period contrasts with other studies and may be related to higher comorbidity in Veterans and/or VA formulary restrictions on the use of transdermal T formulations.

Testosterone treatment of men with mild cognitive impairment and low testosterone levels.

INTRODUCTION: This study investigated the effects of testosterone (T) treatment on cognition, mood, and quality of life in men with mild cognitive impairment (MCI) and low serum T levels. METHODS: A total of 351 community-dwelling men were screened, and 37 men evidenced both MCI and low T of whom 27 agreed for further screening. Twenty-two met all the study inclusion/exclusion criteria and enrolled in a 6-month randomized, double-blind, placebo-controlled study. RESULTS: Total T levels significantly increased in the T treatment group. No significant changes were observed in measures of cognition, mood, or quality of life other than improvement in 1 objective measure of verbal memory (P < .05) and decreased depression symptoms (P < .02) in the treatment group. CONCLUSIONS: Testosterone treatment may modestly improve verbal memory and depression symptoms in men with both MCI and low T.

MRI in a case of osteosarcoma in the temporomandibular joint.

Osteosarcoma of the temporomandibular joint (TMJ) is rare. We report a case of osteosarcoma in the TMJ of a 62-year-old female, pre-operatively diagnosed to have a benign tumour, and discuss the usefulness and limits of MRI using a TMJ coil as a diagnosis.

Effect of ageing on healing of bilateral mandibular condyle fractures in a rat model.

To examine the hypothesis that conservative treatment is applicable to younger patients with bilateral mandibular condylar fractures, we studied the effect of ageing on the healing of bilateral mandibular condylar fractures in a rat model. Male Sprague-Dawley rats aged 3, 6, and 36 weeks (n=25/cohort, total n=75) were divided into a fracture group (n=12) and a sham control group (n=12); one rat from each cohort was used as a normal unoperated control. Cell proliferation was evaluated using the bromodeoxyuridine (BrdU) labelling index (LI). Osteochondrogenesis was assessed by the expression of Indian hedgehog (Ihh), type X collagen, and osteocalcin in the condylar head. Condylar fracture healing was found to be delayed by ageing. BrdU LI values in the fracture groups were higher in younger rats than in older rats at 8 weeks after fracture. The number of Ihh-positive cells in the fracture groups increased significantly up to 2 weeks after fracture, and then gradually decreased until 8 weeks after fracture. The findings of this study support the clinical concept of conservative treatment of bilateral condylar fractures in younger patients, but functional issues regarding ramus height and its consequences on occlusion have not been tested in this study.

Genetic polymorphism in IFNL4 and response to pegylated interferon-α and ribavirin in Japanese chronic hepatitis C patients.

A genetic polymorphism of the newly discovered interferon-λ 4 (IFNL4) gene was associated with hepatitis C virus (HCV) clearance in individuals of African ancestry. To assess whether a dinucleotide variant of IFNL4 (ss469415590) also affected treatment outcome of antiviral therapy in Japan, we genotyped 213 patients with chronic genotype 1 HCV infection and 176 healthy subjects. The ΔG allele was associated with treatment failure [odds ratio (OR) 4.73, P = 0.019], as was the IFL3 rs8099917 single nucleotide polymorphism (SNP) (OR 5.06, P = 0.068). The correlation between ss469415590 and rs8099917 was high (r(2) = 0.92, D' = 0.98). Multivariate analysis revealed that the rs8099917 SNP was independently associated with treatment failure (OR 5.28, P = 0.009). Therefore, ss469415590 may be another predictive marker of antiviral therapy outcome in the Japanese population.

Identification and antimicrobial activity of actinobacteria from soils in southern Thailand.

The aim of this research was to study on the identification and antimicrobial activity of actinobacteria from six soil samples collected around Krung Ching waterfall, Nakhon Si Thammarat province, the southern part of Thailand. Thirty-one isolates of actinobacteria were isolated using the dilution plating method on modified starch casein nitrate agar plates and potato starch-glycerol agar plates. On the primary screening, 9 isolates exhibited the antimicrobial activity against Bacillus subtilis, 8 isolates against Kocuria rhizophila, 6 isolates against Mucor racemosus, 2 isolates against Escherichia coli and Candida albicans and 5 isolates against Xanthomonas campestris pv. oryzae. All the isolates were identified based on their morphological and cultural characteristics including the 16S rRNA gene sequence analysis. Eighteen isolates were identified as Streptomyces, 8 isolates as Nocardia, 2 isolates as Kitasatospora, one of each isolate as Amycolatopsis, Rhodococcus and Gordonia.

Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole.

CONTEXT: The concentration of intratesticular testosterone (IT-T) required for human spermatogenesis is unknown because spermatogenesis can persist despite the markedly reduced IT-T concentrations observed with LH suppression. Methods to lower IT-T further are needed to determine the relationship between IT-T and spermatogenesis. OBJECTIVE: The objective of the study was to determine the effect of inhibiting the synthesis and metabolism of testosterone (T) on IT-T in gonadotropin-suppressed human testes. DESIGN/SETTING/PATIENTS: Forty normal men participated in a blinded, placebo-controlled, randomized trial at an academic center. INTERVENTION/OUTCOME MEASURES: All men were first administered the GnRH antagonist acyline to suppress LH. Forty-eight hours after acyline administration, subjects were randomly assigned to placebo, ketoconazole (to inhibit T synthesis) at 400 or 800 mg, dutasteride (to inhibit T metabolism) 2.5 mg, or anastrazole (to inhibit T metabolism) 1 mg, daily for 7 days (n = 8/group). Intratesticular steroid concentrations were measured 48 hours after acyline administration alone and again after 7 days of combination treatment. RESULTS: After 7 days of combination treatment, the median IT-T (25th, 75th percentile) in the placebo group was 14 (8.0, 21.2) ng/mL. IT-T was reduced to 3.7 (2.5, 7.1) ng/mL in the ketoconazole 400 mg group and 1.7 (0.8, 4.0) ng/mL in the ketoconazole 800 mg group (P < .001 vs placebo for both comparisons). IT-T concentrations in the dutasteride and anastrazole groups were similar to placebo. CONCLUSION: Combining inhibition of steroidogenesis with gonadotropin suppression lowers IT-T more than gonadotropin suppression alone. This combination might be useful to determine the minimum IT-T concentration necessary for human spermatogenesis, information essential for developing male hormonal contraceptives.

Ureteric embolization for lower urinary tract fistulae: use of two amplatzer vascular plugs and N-butyl cyanoacrylate employing the "sandwich" technique.

PURPOSE: This study describes and evaluated the effectiveness of occluding distal ureters in the clinical setting of urinary vaginal (vesicovaginal or enterovesicovaginal) fistulae utilizing a new technique which combines Amplatzer vascular plugs and N-butyl cyanoacrylate. MATERIALS: This is a retrospective study (January 2007-December 2010) of patients with urinary-vaginal fistulae undergoing distal ureter embolization utilizing an Amplatzer-N-butyl cyanoacrylate-Amplatzer sandwich technique. An 8-12-mm type-I or type-II Amplatzer vascular plug was delivered using the sheath and deployed in the ureter distal to the pelvic brim. Instillation of 0.8-1.5 cc of N-butyl cyanoacrylate into ureter proximal to the Amplatzer plug was performed. This was followed by another set of 8-12-mm type-I or type-II Amplatzer vascular plugs in a technique referred to as the "sandwich technique." RESULTS: Five ureters in three patients were occluded utilizing the above-described technique during the 4-year study period. Mean maximum size Amplatzer used per ureter was 10.8 mm (range, 8-12). One ureter required three Amplatzer plugs and the rest required two. Two patients (3 ureters) were clinically successful with complete resolution of symptoms in 36-48 h. The third patient (2 ureters) was partly successful and required a second Amplatzer-N-butyl cyanoacrylate sandwich technique embolization. The mean clinical follow-up was 11.3 months (range, 1.7-29.2). CONCLUSIONS: The Amplatzer-N-butyl cyanoacrylate-Amplatzer sandwich technique for occluding the distal ureter is safe and effective with a quick (probably due to the N-butyl cyanoacrylate) and durable (probably due to the Amplatzer plugs) clinical response.

The maturation of grafted bone after posterior lumbar interbody fusion with an interbody carbon cage: a prospective five-year study.

We evaluated the maturation of grafted bone in cases of successful fusion after a one- or two-level posterior lumbar interbody fusion (PLIF) using interbody carbon cages. We carried out a five-year prospective longitudinal radiological evaluation of patients using plain radiographs and CT scans. One year after surgery, 117 patients with an early successful fusion were selected for inclusion in the study. Radiological evaluation of interbody bone fusion was graded on a 4-point scale. The mean grades of all radiological and CT assessments increased in the five years after surgery, and differences compared to the previous time interval were statistically significant for three or four years after surgery. Because the grafted bone continues to mature for three years after surgery, the success of a fusion should not be assessed until at least three years have elapsed. There were no significant differences in the longitudinal patterns of grafted bone maturity between iliac bone and local bone. However, iliac bone grafting may remodel faster than local bone.

The effect of gonadotropin withdrawal and stimulation with human chorionic gonadotropin on intratesticular androstenedione and DHEA in normal men.

INTRODUCTION: Concentrations of intratesticular (IT) testosterone (T) are known to be 100-200 times those of serum T; however, the IT concentrations of T's precursors, their testicular to serum gradients, gonadotropin dependence, and response to stimulation with human chorionic gonadotropin (hCG) have not been studied in detail. We hypothesized that serum and IT androstenedione (ADD) and IT dehydroepiandrosterone (DHEA) would be significantly suppressed by the administration of a GnRH antagonist and increased when stimulated by hCG, without a similar suppression of serum DHEA. METHODS: We suppressed gonadotropins in 23 normal men with the GnRH antagonist acyline and randomly assigned them to one of four doses of hCG, 0, 15, 60, or 125 IU sc every other day for 10 d. Blood and IT fluid for the measurement of serum and IT hormones were obtained at baseline and after 10 d of treatment. RESULTS: Baseline IT ADD [median (25th, 75th percentile)] was 629 (308, 860) nmol/liter, and IT DHEA was 564 (411, 879) nmol/liter, which were 175 and 27 times higher than their respective serum concentrations. IT ADD and IT DHEA were suppressed by 98 and 82%, respectively, by acyline and significantly increased with hCG administration. Likewise, serum ADD was suppressed by 50%, but serum DHEA was unchanged. DISCUSSION: ADD and DHEA are highly concentrated within the human testes compared with serum. Serum and IT ADD and IT DHEA are markedly suppressed with GnRH administration and stimulated by hCG, but serum DHEA is not, suggesting that most circulating DHEA is not of testicular origin.

Rheolytic Thrombectomy with or without Adjunctive Indwelling Pharmacolysis in Patients Presenting with Acute Pulmonary Embolism Presenting with Right Heart Strain and/or Pulseless Electrical Activity.

Purpose. To evaluate the safety and efficacy of the Possis rheolytic thrombectomy with or without indwelling catheter-directed pharmacolysis for the treatment of massive pulmonary embolus in patients presenting with right heart strain and/or a pulseless electrical activity (PEA). Materials and Methods. Retrospective review of patients undergoing pulmonary pharmacolysis was performed (07/2004-06/2009). Pre- and posttreatment Miller index scoring weres calculated and compared. Patients were evaluated for tPA doses, ICU stay, hospital stay, and survival by Kaplan-Meier analysis. Results. 11 patients with massive PE were found, with 10/11 presenting with a Miller score of >17 (range: 16-27, mean: 23.2). CTPA and/or echocardiographic evidence of right heart strain was found in 10/11 patients. 3 (27%) patients presented with a PEA event. Two (18%) patients had a contraindication to pharmacolysis and were treated with mechanical thrombectomy alone. The intraprocedural mortality was 9% (n = 1/11). Of the 10 patients who survived the initial treatment, 7 patients underwent standard mechanical thrombectomy initially, while 5 received power pulse spray mechanical thrombectomy. Eight of these 10 patients underwent adjunctive indwelling catheter-directed thrombolysis. The mean catheter-directed infusion duration was 18 hours (range of 12-26 hours). The average intraprocedural, infusion, and total doses of tPA were 7 mg, 19.7 mg, and 26.7 mg, respectively. There was a 91% (10/11) technical success rate. The failure was the single mortality. Average reduction in Miller score was 9.5 or 41% (P = 0.009), obstructive index of 6.4 or 47% (P = 0.03), and perfusion index of 2.7 or 28% (P = 0.05). Average ICU and hospital stay were 7.4 days (range 2-27 days) and 21.3 days (range 6-60 days), respectively. Intent to treat survival was 90% at 6, 12, and 18 months. Conclusion. Rheolytic thrombectomy with or without adjunctive catheter-directed thrombolysis provides a safe and effective method for treatment of acute PE in patients who present with right heart strain and/or a PEA event.