Single-injection or continuous femoral nerve block for total knee arthroplasty?

BACKGROUND: The ideal local anesthetic regime for femoral nerve block that balances analgesia with mobility after total knee arthroplasty (TKA) remains undefined. QUESTIONS/PURPOSES: We compared two volumes and concentrations of a fixed dose of ropivacaine for continuous femoral nerve block after TKA to a single injection femoral nerve block with ropivacaine to determine (1) time to discharge readiness; (2) early pain scores and analgesic consumption; and (3) functional outcomes, including range of motion and WOMAC scores at the time of recovery. METHODS: Ninety-nine patients were allocated to one of three continuous femoral nerve block groups for this randomized, placebo-controlled, double-blind trial: a high concentration group (ropivacaine 0.2% infusion), a low concentration group (ropivacaine 0.1% infusion), or a placebo infusion group (saline 0.9% infusion). Infusions were discontinued on postoperative Day (POD) 2. The primary outcome was time to discharge readiness. Secondary outcomes included opioid consumption, pain, and functional outcomes. Ninety-three patients completed the study protocol; the study was halted early because of unanticipated changes to pain protocols at the host institution, by which time only 61% of the required number of patients had been enrolled. RESULTS: With the numbers available, the mean time to discharge readiness was not different between groups (high concentration group, 62 hours [95% confidence interval [CI], 51-72 hours]; low concentration group, 73 hours [95% CI, 63-83 hours]; placebo infusion group 65 hours [95% CI, 56-75 hours]; p = 0.27). Patients in the low concentration group consumed significantly less morphine during the period of infusion (POD 1, high concentration group, 56 mg [95% CI, 42-70 mg]; low concentration group, 35 mg [95% CI, 27-43 mg]; placebo infusion group, 48 mg [95% CI, 38-59 mg], p = 0.02; POD 2, high concentration group, 50 mg [95% CI, 41-60 mg]; low concentration group, 33 mg [95% CI, 24-42 mg]; placebo infusion group, 39 mg [95% CI, 30-48 mg], p = 0.04); however, there were no important differences in pain scores or opioid-related side effects with the numbers available. Likewise, there were no important differences in functional outcomes between groups. CONCLUSIONS: Based on this study, which was terminated prematurely before the desired sample size could be achieved, we were unable to demonstrate that varying the concentration and volume of a fixed-dose ropivacaine infusion for continuous femoral nerve block influences time to discharge readiness when compared with a conventional single-injection femoral nerve block after TKA. A low concentration of ropivacaine infusion can reduce postoperative opioid consumption but without any important differences in pain scores, side effects, or functional outcomes. These pilot data may be used to inform the statistical power of future randomized trials. LEVEL OF EVIDENCE: Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

ALDH1A3 loss of function causes bilateral anophthalmia/microphthalmia and hypoplasia of the optic nerve and optic chiasm.

The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease. We used homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes. We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems.

Alveolar overdistension as a cause of lung injury: differences among three animal species.

This study analyses characteristics of lung injuries produced by alveolar overdistension in three animal species. Mechanical ventilation at normal tidal volume (10 mL/Kg) and high tidal volume (50 mL/Kg) was applied for 30 min in each species. Data were gathered on wet/dry weight ratio, histological score, and area of alveolar collapse. Five out of six rabbits with high tidal volume developed tension pneumothorax, and the rabbit results were therefore not included in the histological analysis. Lungs from the pigs and rats showed minimal histological lesions. Pigs ventilated with high tidal volume had significantly greater oedema, higher neutrophil infiltration, and higher percentage area of alveolar collapse than rats ventilated with high tidal volume. We conclude that rabbits are not an appropriate species for in vivo studies of alveolar overdistension due to their fragility. Although some histological lesions are observed in pigs and rats, the lesions do not appear to be relevant.

Histopathological examination of nerve samples from pure neural leprosy patients: obtaining maximum information to improve diagnostic efficiency

Nerve biopsy examination is an important auxiliary procedure for diagnosing pure neural leprosy (PNL). When acid-fast bacilli (AFB) are not detected in the nerve sample, the value of other nonspecific histological alterations should be considered along with pertinent clinical, electroneuromyographical and laboratory data (the detection of Mycobacterium leprae DNA with polymerase chain reaction and the detection of serum anti-phenolic glycolipid 1 antibodies) to support a possible or probable PNL diagnosis. Three hundred forty nerve samples [144 from PNL patients and 196 from patients with non-leprosy peripheral neuropathies (NLN)] were examined. Both AFB-negative and AFB-positive PNL samples had more frequent histopathological alterations (epithelioid granulomas, mononuclear infiltrates, fibrosis, perineurial and subperineurial oedema and decreased numbers of myelinated fibres) than the NLN group. Multivariate analysis revealed that independently, mononuclear infiltrate and perineurial fibrosis were more common in the PNL group and were able to correctly classify AFB-negative PNL samples. These results indicate that even in the absence of AFB, these histopathological nerve alterations may justify a PNL diagnosis when observed in conjunction with pertinent clinical, epidemiological and laboratory data.

Cutaneous lesions sensory impairment recovery and nerve regeneration in leprosy patients

It is important to understand the mechanisms that enable peripheral neurons to regenerate after nerve injury in order to identify methods of improving this regeneration. Therefore, we studied nerve regeneration and sensory impairment recovery in the cutaneous lesions of leprosy patients (LPs) before and after treatment with multidrug therapy (MDT). The skin lesion sensory test results were compared to the histopathological and immunohistochemical protein gene product (PGP) 9.5 and the p75 nerve growth factor receptors (NGFr) findings. The cutaneous neural occupation ratio (CNOR) was evaluated for both neural markers. Thermal and pain sensations were the most frequently affected functions at the first visit and the most frequently recovered functions after MDT. The presence of a high cutaneous nerve damage index did not prevent the recovery of any type of sensory function. The CNOR was calculated for each biopsy, according to the presence of PGP and NGFr-immunostained fibres and it was not significantly different before or after the MDT. We observed a variable influence of MDT in the recovery from sensory impairment in the cutaneous lesions of LPs. Nociception and cold thermosensation were the most recovered sensations. The recovery of sensation in the skin lesions appeared to be associated with subsiding inflammation rather than with the regenerative activity of nerve fibres.

Alveolar echinococcosis of the liver: diffusionweighted MR imaging findings

Purpose: To report the diffusion-weighted MR imaging (DWI) findings in hepatic alveolar echinococcosis (AE). To evaluate the usefulness of apparent diffusion coefficients (ADCs) for differentiating the 5 types of AE lesions (as reported by Kodama, Radiology, 2003).Methods and Materials: We retrospectively included 17 patients (10 women, mean age 64.3years) with 48 AE liver lesions (>1cm2) that had been investigated by 3-Tesla MR imaging between March 2008 and August 2011 performing our standard protocol including DWI (b-values: 0, 300 and 600s/mm2). In consensus, two radiologists assessed lesion characteristics such as diameter, cystic and/or fibrotic components including Kodama classification, signal intensity, contrast enhancement, calcifications (on CT), and measured the ADC of each lesion. AE was confirmed by serology, biopsy and/or surgery in all patients.Results: Seventeen lesions of Kodama type 1, 10 of type 2, 19 of type 3, 1 of type 4 and 1 of type 5 were found. Mean(±SD) ADC of all AE lesions was 1.75±0.45 ×10-3mm2/s. Mean(±SD) ADCs of Kodama type 1, 2, 3, 4 and 5 lesions were 1.74±0.55, 1.71±0.49, 1.82±0.36, 1.46±0 and 1.43±0 ×10-3mm2/s, respectively. No significant difference was noted between the different Kodama types (p=0.89). Presence of fibrotic (p=0.24) and/or calcified (p=0.90) components, or contrast enhancement (p=0.84) of AE lesions were not correlated with significant differences in ADCs.Conclusion: ADCs of AE lesions are relatively low compared to other cystic liver lesions, which is helpful in suggesting the diagnosis. However, ADCs were not found to be useful for differentiating Kodama types of AE lesions.

New sonographic measures of peripheral nerves: a tool for the diagnosis of peripheral nerve involvement in leprosy

To evaluate ultrasonographic (US) cross-sectional areas (CSAs) of peripheral nerves, indexes of the differences between CSAs at the same point (∆CSAs) and between tunnel (T) and pre-tunnel (PT) ulnar CSAs (∆TPTs) in leprosy patients (LPs) and healthy volunteers (HVs). Seventy-seven LPs and 49 HVs underwent bilateral US at PT and T ulnar points, as well as along the median (M) and common fibular (CF) nerves, to calculate the CSAs, ∆CSAs and ∆TPTs. The CSA values in HVs were lower than those in LPs (p < 0.0001) at the PT (5.67/9.78 mm2) and T (6.50/10.94 mm2) points, as well as at the M (5.85/8.48 mm2) and CF (8.17/14.14 mm2) nerves. The optimum CSA- receiver operating characteristic (ROC) points and sensitivities/specificities were, respectively, 6.85 mm2 and 68-85% for the PT point, 7.35 mm2 and 71-78% for the T point, 6.75 mm2 and 62-75% for the M nerve and 9.55 mm2 and 81-72% for the CF nerve. The ∆CSAs of the LPs were greater than those of the HVs at the PT point (4.02/0.85; p = 0.007), T point (3.71/0.98; p = 0.0005) and CF nerve (2.93/1.14; p = 0.015), with no difference found for the M nerve (1.41/0.95; p = 0.17). The optimum ∆CSA-ROC points, sensitivities, specificities and p-values were, respectively, 1.35, 49%, 80% and 0.003 at the PT point, 1.55, 55-85% and 0.0006 at the T point, 0.70, 58-50% and 0.73 for the M nerve and 1.25, 54-67% and 0.022 for the CF nerve. The ∆TPT in the LPs was greater than that in the HVs (4.43/1.44; p <0.0001). The optimum ∆TPT-ROC point was 2.65 (90% sensitivity/41% specificity, p < 0.0001). The ROC analysis of CSAs showed the highest specificity and sensitivity at the PT point and CF nerve, respectively. The PT and T ∆CSAs had high specificities (> 80%) and ∆TPT had the highest specificity (> 90%). New sonographic peripheral nerve measurements (∆CSAs and ∆TPT) provide an important methodological improvement in the detection of leprosy neuropathy.

How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i) skin; (ii) cartilage; (iii) bone; (iv) nerve; and (v) cardiac.

Isolated trochlear nerve palsy secondary to dural carotid-cavernous sinus fistula.

Ophthalmoplegia associated with dural carotid-cavernous sinus fistula typically involves the third, fourth, and sixth cranial nerves. Occasionally, isolated palsy of the oculomotor or abducens nerve is noted. We report a patient with bilateral dural carotid-cavernous sinus fistulas who presented with an isolated trochlear nerve palsy.

Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alveolar bone resorption by mitochondrial-related mechanisms.

BACKGROUND/OBJECTIVES Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old) and old (24 months old) rats. METHODS/FINDINGS Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA) as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA), as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations. CONCLUSIONS The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease) associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.

Osteosarcoma extraóseo en extremidad inferior

INTRODUCTION: Extraoseus osteosarcoma is a rare tumor confined in soft tissues but with histological features similar to bone osteosarcoma. CLINICAL CASE: We report the case of a young male affected extraosseous osteosarcoma. A detailed analysis of the clinical symptoms and evolution from the beginning of the process to the death of the patient, three years later, is performed. DISCUSSION: The different types of treatment and prognostic factors involving this disease are discussed CONCLUSIONS: Radical surgery followed by chemotherapy is the preferred form of treatment in extraosseus osteosarcoma.The latest advances in chemotherapy have improved the prognosis in this type of tumor

Neuroprotection for optic nerve disorders.

The concept that optic nerve fiber loss might be reduced by neuroprotection arose in the mid 1990s. The subsequent research effort, focused mainly on rodent models, has not yet transformed into a successful clinical trial, but provides mechanistic understanding of retinal ganglion cell death and points to potential therapeutic strategies. This review highlights advances made over the last year. In excitotoxicity and axotomy models retinal ganglion cell death has been shown to result from a complex interaction between retinal neurons and Müller glia, which release toxic molecules including tumor necrosis factor alpha. This counteracts neuroprotection by neurotrophins such as nerve growth factor, which bind to p75NTR receptors on Müller glia stimulating the toxic release. Another negative effect against neurotrophin-mediated protection involves the action of LINGO-1 at trkB brain-derived neurotrophic factor (BDNF) receptors, and BDNF neuroprotection is enhanced by an antagonist to LINGO-1. As an alternative to pharmacotherapy, retinal defences can be stimulated by exposure to infrared radiation. The mechanisms involved in glaucoma and other optic nerve disorders are being clarified in rodent models, focusing on retrograde degeneration following axonal damage, excitotoxicity and inflammatory/autoimmune mechanisms. Neuroprotective strategies are being refined in the light of the mechanistic understanding.

Painful total hip replacement due to sciatic nerve entrapment in scar tissue and lipoma.

Painful total hip replacement remains a challenging problem because of the large amount of possible diagnoses. We report about a 64-year-old female patient who was misdiagnosed during 4 years as psychiatric. She suffered of excruciating left retrotrochanteric pain after the implantation of a cementless total hip replacement and revision because of recurrent hip dislocations. Walking was limited to short distances using two crutches. The work-up at this time included the usual diagnoses and remained unsuccessful. No loosening, infection or malposition of the prosthesis could be found, and she had no neurologic deficits in her operated leg. An MRI was obtained to visualize the retrotrochanteric soft tissues and showed a tight scar surrounding the sciatic nerve, which was also compressed by an adjacent lipoma. Therefore, she was reoperated on to remove the lipoma and the scar tissue around the sciatic nerve. To decrease the risk of recurrent scarring around the sciatic nerve, an adhesion barrier was applied before closure. One year after the operation, the patient has no neurologic deficit, no more pain and is able to walk unlimited distances without crutches. Scar tissue around the sciatic nerve is frequently observed during revision surgery. However, we feel that sciatic nerve entrapment by scar tissue should be a part of the differential diagnosis of painful THR. MRI may be a useful tool to achieve this diagnosis.