Diabetic foot ulcers treated with hyperbaric oxygen therapy: a review of the literature

Hyperbaric oxygen therapy (HBO) has been used as an adjunct for healing diabetic foot ulcers (DFUs) for decades. However, its use remains controversial. A literature search was conducted to locate clinical studies and assess the available evidence. Ten prospective and seven retrospective studies evaluating HBO for DFUs were located. These were reviewed and the outcomes were discussed. One study reported no difference in outcomes between patients receiving hyperbaric oxygen and the control group. However, their regime differed from all other studies in that the patients received hyperbaric oxygen twice rather than once daily. Reduced amputation rates and improved healing were the most common outcomes observed.     

Intrathoracic papillary thyroid carcinoma from occult primary disease

A 42-year-old woman undertook a chest radiograph for a routine evaluation prior to surgery for pelvic endometrioma, which revealed a right paratracheal mass slightly displacing the trachea to the left. CT of the thorax disclosed a well demarcated, heterogeneous, lobular, right paratracheal mass, bearing punctate, coarse, and curvilinear calcifications. MRI further revealed two components within the lesion: a larger, cystic, exhibiting thin septations, and a solid component at the lower part exhibiting strong enhancement. No continuity of the mass with the thyroid gland was demonstrated, which had normal size and no focal lesion. Histological examination of the resected mass disclosed lymph node tissue infiltrated by papillary thyroid carcinoma; subsequent total thyroidectomy revealed small foci of papillary carcinoma within both lobes of the thyroid gland. Ablative dose I-131 was administered and the patient was put on daily thyroid supplements.     

Understanding bone safety zones during bone marrow aspiration from the iliac crest: the sector rule

Purpose

Should the trocar suddenly lose contact with bone during bone marrow aspiration, it may result in visceral injury. The anatomy of the ilium and the structures adjacent to the iliac bone were studied to determine the danger of breach by a trocar introduced into the iliac crest.

Methods

The authors followed two series of patients, one series to do measurements of distance and angles of the structures at risk to the iliac bone and the other to evaluate the risk of a trocar being directed outside the iliac wing during bone marrow aspiration. The authors also examined 24 pelvices by computed tomography (CT) scans of mature adults (48 iliac crests). Lines dividing the iliac wing into six equal sectors were used to form sectors (e.g. sector 1 anterior, sector 6 posterior). Vascular or neurological structures were considered at risk if they were accessible to the tip of a 10-cm trocar introduced into the iliac crest with a possible deviation of 20° from the plane of the iliac wing on the three-dimensional reconstruction. The authors tracked bone marrow aspiration of six different surgeons and calculated among 120 patients (480 entry points) the number of times the needle lost contact with bone in each sector of aspiration.

Results

The sector system reliably predicted safe and unsafe areas for trocar placement. Among the 480 entry points in the 120 patients, 94 breaches were observed and higher risks were observed in the thinner sectors. The risk was also higher in obese patients and the risk decreased with more experienced surgeons. The trocar could reach the external iliac artery on pelvic CT scans in the four most anterior sectors with a higher frequency in women. Posterior sectors were at risk for sciatic nerve and gluteal vessel damage when the trocar was pushed deeper than 6 cm into the posterior iliac crest. In cadavers, the dissection demonstrated nine vascular or neurological lesions.

Conclusions

Using the sector system, trocars can be directed away from neural and vascular structures and toward zones that are likely to contain larger bone marrow stock.     

Trabecular Bone Score and Hip Structural Analysis in Patients With Atypical Femur Fractures

Bisphosphonate use has declined dramatically in recent years, partly because of fear of rare side effects like atypical femur fractures (AFFs). It is therefore desirable to have a diagnostic method to identify those at risk of AFF to prevent this serious complication. We compared trabecular microarchitecture and hip geometry between 30 patients with AFF and 141 controls of similar age and sex, using bisphosphonates. Trabecular bone score (TBS) and hip structural analysis (HSA) were used to assess trabecular microarchitecture and macroscopic hip geometry from dual-energy X-ray absorptiometry images of the lumbar spine and hip, respectively. General characteristics, TBS, and HSA were compared between patients with AFF and controls using Student's t tests and chi-square statistics. Associations between AFF and TBS and femur geometric characteristics by HSA were adjusted for sex, age, height, weight, ethnicity, duration of bisphosphonate use, and glucocorticoid use. Additionally, the analysis of TBS was adjusted for lumbar spine bone mineral density and the time difference between dual-energy X-ray absorptiometry scanning and the diagnosis of AFF. Patients with AFF had significantly higher body mass index than controls, had used bisphosphonates longer, and glucocorticoids and proton pump inhibitors more frequently. Sex-specific T-score was significantly higher in patients with AFF at the lumbar spine (p?=?0.004), but not at the femoral neck (p?=?0.190) after adjustment for age, height, and weight. TBS did not differ significantly between patients with AFF and controls. Neither neck shaft angle nor any geometric variables at the femoral shaft measured by HSA differed between patients with AFF and controls. At the narrow neck, patients with AFF had lower buckling ratio and higher centroid position, consistent with a lower risk of classical fragility hip fractures. The findings at narrow neck and higher bone mineral density might be explained by the fact that the majority of patients with AFF used bisphosphonates to prevent glucocorticoid-induced osteoporosis. Based on our results, TBS and HSA do not appear to have value in detecting patients at risk of AFF.     

Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single‐center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r‐ATG/EVR, n = 88), or mycophenolate (r‐ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy‐proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06–0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r‐ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r‐ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).     

Predictive Value of Four Kallikrein Markers for Pathologically Insignificant Compared With Aggressive Prostate Cancer in Radical Prostatectomy Specimens: Results From the European Randomized Study of Screening for Prostate Cancer Section Rotterdam

Background

Treatment decisions can be difficult in men with low-risk prostate cancer (PCa).

Objective

To evaluate the ability of a panel of four kallikrein markers in blood—total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2—to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries.

Design, setting, and participants

The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004.

Outcome measurements and statistical analysis

We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3–T4, extracapsular extension, tumor volume >0.5 cm³, or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood.

Results and limitations

A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model.

Conclusions

Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment.     

High-resolution MRI and micro-CT in an ex vivo rabbit anterior cruciate ligament transection model of osteoarthritis

OBJECTIVE: The aim of this study was to investigate the potential of using non-invasive, multi-modality imaging techniques to quantify disease progression in a rabbit model of experimentally induced osteoarthritis (OA). METHODS: High-resolution 4-T magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) techniques were implemented and validated in an ex vivo rabbit anterior cruciate ligament transection (ACLT) model of OA. A three-dimensional (3-D) rigid body registration technique was executed and evaluated to allow combined MR-CT analysis in co-registered image volumes of the knee. RESULTS: The 3-D MRI and micro-CT data formats made it possible to quantify cartilage damage, joint-space, and osseous changes in the rabbit ACLT model of OA. Spoiled gradient-recalled echo and fast-spin echo (FSE) sequences were jointly used to evaluate femorotibial cartilage and determine the sensitivity (78.3%) and specificity (95.3%) of 4-T MRI to detect clinically significant cartilage lesions. Overall precision error of the micro-CT technique for analysis of joint-space, volumetric bone mineral density (vBMD), and bone volume fraction (BV/TV) was 1.8%, 1.2%, and 2.0%, respectively. Co-registration of the 3-D data sets was achieved to within 0.36 mm for completed intermodality registrations, 0.22 mm for extrapolated intramodality registrations, and 0.50mm for extrapolated intermodality registrations. CONCLUSIONS: These results indicate that high-resolution 4-T MRI and micro-CT can be used to accurately quantify cartilage damage and calcified tissue changes in the rabbit ACLT model of OA. In addition, image volumes can be successfully co-registered to facilitate a comprehensive multi-modality examination of localized changes in both soft tissue and bone within the rabbit femorotibial joint.     

Reduced variability of acetabular cup positioning with use of an imageless navigation system

Positioning the acetabular component is one of the most important steps in total hip arthroplasty; malpositioned components can result in dislocations, impingement, limited range of motion, and increased polyethylene wear. Conventional surgery makes use of specialized alignment guides provided by the manufacturers of the implants. The use of mechanical guides has been shown to result in large variations of cup inclination and version. We investigated acetabular cup alignment with the nonimage-based hip navigation system compared with a conventional mechanically guided procedure in 12 human cadavers. Postoperative cup position relative to the pelvic reference plane was assessed in both groups with the use of a three-dimensional digitizing arm. In the navigated group, a median inclination of 45.5 degrees and a median anteversion of 21.9 degrees (goals, 45 degrees and 20 degrees) were reached. In the control group, the median inclination was 41.8 degrees and the median anteversion was 24.6 degrees. The ninetieth percentile showed a much wider range for the control group (36.1 degrees-51.8 degrees inclination, 15 degrees-33.5 degrees anteversion) than for the navigated group (43.9 degrees-48.2 degrees inclination, 18.3 degrees-25.4 degrees anteversion). This cadaver study shows that computer-assisted cup positioning using a nonimage-based hip navigation system allowed for more consistent placement of the acetabular component.     

Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta‐analysis

Schwannomatosis is a genetic disorder characterized by the occurrence of multiple peripheral schwannomas. Segmental schwannomatosis is diagnosed when schwannomas are restricted to 1 extremity and is thought to be caused by genetic mosaicism. We studied 5 patients with segmental schwannomatosis through microstructural magnetic resonance neurography and mutation analysis of NF2, SMARCB1, and LZTR1. In 4 of 5 patients, subtle fascicular nerve lesions were detected in clinically unaffected extremities. Two patients exhibited LZTR1 germline mutations. This appears contrary to a simple concept of genetic mosaicism and suggests more complex and heterogeneous mechanisms underlying the phenotype of segmental schwannomatosis than previously thought. Ann Neurol 2016;80:625–628     

Four of the six Drosophila rhodopsin‐expressing photoreceptors can mediate circadian entrainment in low light

Light is the major stimulus for the synchronization of circadian clocks with day–night cycles. The light‐driven entrainment of the clock that controls rest–activity rhythms in Drosophila relies on different photoreceptive molecules. Cryptochrome (CRY) is expressed in most brain clock neurons, whereas six different rhodopsins (RH) are present in the light‐sensing organs. The compound eye includes outer photoreceptors that express RH1 and inner photoreceptors that each express one of the four rhodopsins RH3–RH6. RH6 is also expressed in the extraretinal Hofbauer–Buchner eyelet, whereas RH2 is only found in the ocelli. In low light, the synchronization of behavioral rhythms relies on either CRY or the canonical rhodopsin phototransduction pathway, which requires the phospholipase C‐β encoded by norpA (no receptor potential A). We used norpA^P24 cry⁰² double mutants that are circadianly blind in low light and restored NORPA function in each of the six types of photoreceptors, defined as expressing a particular rhodopsin. We first show that the NORPA pathway is less efficient than CRY for synchronizing rest–activity rhythms with delayed light–dark cycles but is important for proper phasing, whereas the two light‐sensing pathways can mediate efficient adjustments to phase advances. Four of the six rhodopsin‐expressing photoreceptors can mediate circadian entrainment, and all are more efficient for advancing than for delaying the behavioral clock. In contrast, neither RH5‐expressing retinal photoreceptors nor RH2‐expressing ocellar photoreceptors are sufficient to mediate synchronization through the NORPA pathway. Our results thus reveal different contributions of rhodopsin‐expressing photoreceptors and suggest the existence of several circuits for rhodopsin‐dependent circadian entrainment. J. Comp. Neurol. 524:2828–2844, 2016. © 2016 Wiley Periodicals, Inc.