Treatment of presumed aseptic non-union of the humeral shaft by osteosynthesis combining intramedullary nailing and screw plate.

In 2020, the most common treatment for presumed aseptic non-union of the humeral shaft seems to be decortication, often associated with bone autografting, and stabilized by a screw plate. We propose to evaluate an original technique of rigid osteosynthesis combining intramedullary nailing and screw plate. Between January 2004 and January 2020, 45 patients underwent treatment of presumed aseptic non-union of the humeral shaft by osteosynthesis combining intramedullary nailing and a screw plate. The minimum radio-clinical follow-up was one year postoperatively. The series included 19 men and 26 women with a mean age of 53 years (range 19-84 years). Bone consolidation was achieved in 43 patients, a rate of 95.5%. Comparing patients who achieved bone consolidation with the two failed consolidations did not reveal any statistically significant factor. Interobserver agreement was almost perfect (k=0.93) for the use of the RUST for humeral shaft fractures treated with intramedullary nailing and screw plate. In our study, the treatment of presumed aseptic non- union of the humeral shaft with an osteosynthesis combining intramedullary nailing and screw plate gives, with 95.5% of bone consolidation, results equal to or even superior to the different treatments currently described in the literature.

Infection recurrence factors in one- and two-stage total knee prosthesis exchanges.

PURPOSE: Revision of infected total knee replacements (TKR) is usually delayed for a period in which the joint space is filled with an antibiotic-loaded acrylic spacer. In contrast, one-stage re-implantation supposes immediate re-implantation. Formal comparisons between the two methods are scarce. A retrospective multi-centre study was conducted to investigate the effects of surgery type (one-stage vs. two-stage) on cure rates. It was hypothesised that this parameter would not influence the results. METHOD: All infected TKR, treated consecutively between 2005 and 2010 by senior surgeons working in six referral hospitals, were included retrospectively. Two hundred and eighty-five patients, undergoing one-stage or two-stage TKR, with more than 2-year follow-up (clinical and radiological) were eligible for data collection and analysis. Of them, 108 underwent one-stage and 177 received two-stage TKR. Failure was defined as infection recurrence or persistence of the same or unknown pathogens. Factors linked with infection recurrence were analysed by uni- and multi-variate logistic regression with random intercept. RESULTS: Factors associated with infection recurrence were fistulae (odds ratio (OR) 3.4 [1.2-10.2], p = 0.03), infection by gram-negative bacteria (OR 3.3 [1.0-10.6], p = 0.05), and two-stage surgery with static spacers (OR 4.4 [1.1-17.9], p = 0.04). Gender and type of surgery interacted (p = 0.05). In men (133 patients), type of surgery showed no significant linkage with infection recurrence. In women (152 patients), two-stage surgery with static spacers was associated independently with infection recurrence (OR 5.9 [1.5-23.6], p = 0.01). Among patients without infection recurrence, International Knee Society scores were similar between those undergoing one-stage or two-stage exchanges. CONCLUSION: Two-stage procedures offered less benefit to female patients. It suggests that one-stage procedures are preferable, because they offer greater comfort without increasing the risk of recurrence. Routine one-stage procedures may be a reasonable option in the treatment of infected TKR. LEVEL OF EVIDENCE: III.

p38ß (MAPK11) mediates gemcitabine-associated radiosensitivity in sarcoma experimental models.

BACKGROUND AND PURPOSE: Gemcitabine is an antitumour agent currently used in the treatment of several types of cancer with known properties as a radiosensitizer. p38MAPK signalling pathway has been shown to be a major determinant in the cellular response to gemcitabine in different experimental models. However, the molecular mechanism implicated in gemcitabine-associated radiosensitivity remains unknown. MATERIALS AND METHODS: The human sarcoma cell lines A673 and HT1080, and a mouse cell line derived from a 3-methylcholanthrene induced sarcoma were used as experimental models. Modulation of p38MAPKs was performed by pharmacological approaches (SB203580) and genetic interference using lentiviral vectors coding for specific shRNAs. Viability was assessed by MTT. Gene expression was evaluated by western blot and RT-qPCR. Induction of apoptosis was monitored by caspase 3/7 activity. Response to ionizing radiation was evaluated by clonogenic assays. RESULTS: Our data demonstrate that chemical inhibition of p38MAPK signalling pathway blocks gemcitabine radiosensitizing potential. Genetic interference of MAPK14 (p38α), the most abundantly expressed and best characterized p38MAPK, despite promoting resistance to gemcitabine, it does not affect its radiosensitizing potential. Interestingly, specific knockdown of MAPK11 (p38ß) induces a total loss of the radiosensitivity associated to gemcitabine, as well as a marked increase in the resistance to the drug. CONCLUSION: The present work identifies p38ß as a major determinant of the radiosensitizing potential of gemcitabine without implication of p38α, suggesting that p38ß status should be analysed in those cases in which gemcitabine is combined with ionizing radiation.

MRI prostate contouring is not impaired by the use of a radiotherapy image acquisition set-up. An intra- and inter-observer paired comparative analysis with diagnostic set-up images.

PURPOSE: The use of MRI for radiotherapy planning purposes is growing but image acquisition using radiotherapy set-ups has impaired image quality. Whether differences in image acquisition set-up could modify organ contouring has not been evaluated. Therefore, we aimed to evaluate differences in contouring between paired of image sets that were acquired in the same scanning session using different parameters. MATERIAL AND METHODS: Ten patients underwent RT treatment planning with MRI co-registration. MRI was carried out using two different set-ups during the same session, MRI radiotherapy set-ups and MRI diagnostic set-ups. Prostates and rectums were retrospectively contoured in both image sets by 5 radiation oncologists and 4 radiologists. Intra-observer analysis was carried out comparing organ volumes, the Dice coefficient and hausdorff distance values between two contouring rounds. Inter-observer analysis was carried out by comparing individual contours to a generated STAPLE consensus contour, which is considered the gold standard reference. RESULTS: No significant differences were observed between MRI acquisition set-ups. Significant differences were observed for the dice and hausdorff parameters, comparing individual contours to the STAPLE consensus contour, when analysing diagnostic images between rounds, although raw values were similar. CONCLUSION: Prostate and rectum contours did not differ significantly when using diagnostic or radiotherapy MRI acquisition set-ups.

Discovery of potent and selective histamine H3 receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold.

A novel series of potent histamine H(3) receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold has been discovered. Several compounds display high selectivity over other histamine receptor subtypes and have favorable physicochemical properties, low potential for CYP450 enzyme inhibition and high metabolic stability in microsomal preparations. (R)-2-Cyclopropylmethyl-8-(1-isopropyl-piperidin-4-yloxy)-3-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (8t) showed good in vivo efficacy after per os application in an acute rat dipsogenia model of water intake.

Acoustic probing of the particle concentration in turbulent granular suspensions in air.

Dilute gas-particle suspensions in which the particles are carried by the fluid are found in various industrial and geophysical contexts. One fundamental issue that limits our understanding of such systems is the difficulty to obtain information on the particle concentration inside these often optically opaque suspensions. To overcome this difficulty, we develop ultrasonic spectroscopy to monitor the local particle concentration [Formula: see text] of glass particles (with diameters [Formula: see text] 77 [Formula: see text]m or 155 [Formula: see text]m) suspended in air. First, we determine the minimal air velocity, [Formula: see text], necessary to suspend the particles from the maximum decrease in the transmitted wave amplitude and velocity of ultrasound propagating through the suspension. Next, setting the air velocity at [Formula: see text], we increase the mass of particles and monitor acoustically the local solid volume fraction, [Formula: see text], by measuring the ultrasound wave attenuation coefficient and phase velocity as a function of frequency on the basis of classical scattering and hydrodynamic models. For the frequency ranges and suspensions considered here, the viscous dissipation dominates over scattering and thermal conduction losses. We show that, for a characteristic air velocity [Formula: see text], the locally measured [Formula: see text] reaches a critical value, in agreement with a recent study on turbulent gas-particle mixtures. Moreover, we find that this critical [Formula: see text] increases with the size of the particles. Finally, analysis of the temporal fluctuations of the locally measured solid volume fraction, suggests that high density regions (clusters) are present even in suspensions with concentrations below the critical concentration. This differs from the current hypothesis according to which the critical concentration coincides with the onset of cluster formation.

Radiotherapy is safe in patients with implantable cardiac devices. Analysis of a systematic interrogation follow-up.

INTRODUCTION: The number of patients who have a cardiac implantable electronic device (CIEDs) that undergo a course of radiotherapy is increasing due to the ageing population. The majority of clinical studies only evaluate any CIED malfunction at the end of a course of irradiation or in a case of there being symptoms of possible malfunction. As a result, little data has been collected on CIED status acquired during an active course of irradiation. MATERIAL AND METHODS: We aimed to evaluate the correct functioning of a CIED during a course of radiotherapy. So, a retrospective analysis was made of all patients having CIEDS in a single institution during their course of radiotherapy. All CIEDs were systematically checked before and during the course of radiotherapy according to the risk of device failure and patient dependence. RESULTS: Data was analysed from 56 patients (43 men, 13 women) with a mean age of 78.2 years, of whom 87.5% of the patients carried a pacemaker (PM), the 39% of the patients were PM dependent, and the remaining patients carried an implantable cardioverter-defibrillator (ICD). An observable dose of irradiation was evident in only 10 cases. 69.1% of the CIEDs were checked daily and the remainder were checked weekly. During the radiotherapy course, 82% of the patients did not complain of any cardiological event. The CIED of five patients experienced an increase in the threshold and, in another case, a sudden reduction in the duration of the battery was reported. Another patient with a CIED experienced a cardiac insufficiency episode triggered by a ventricular tachycardia. CONCLUSION: In conclusions, although adverse clinical events from exposure of a CIED to irradiation are rare, they can appear in any group of risk. No dose-dependency was observed on the malfunction of the CIED.

P53 pathway is a major determinant in the radiosensitizing effect of Palbociclib: Implication in cancer therapy.

Targeting cell cycle has become one of the major challenges in cancer therapy, being Palbociclib, a CDK4/6 inhibitor, an excellent example. Recently, it has been reported that Palbociclib could be a novel radiosensitizer agent. In an attempt to clarify the molecular basis of this effect we have used cell lines from colorectal (HT29, HCT116) lung (A549, H1299) and breast cancer (MCF-7). Our results indicate that the presence of a p53 wild type is strictly required for Palbociclib to exert its radiosensitizing effect, independently of the inhibitory effect exerted on CDK4/6. In fact, abrogation of p53 in cells with functional p53 blocks the radiosensitizing effect of Palbociclib. Moreover, no radiosensitizing effect is observed in cells with non-functional p53, but restoration of p53 function promotes radiosensitivity associated to Palbociclib. Furthermore, the presence of Palbociclib blocks the transcriptional activity of p53 in an ATM-dependent-fashion after ionizing radiation exposure, as the blockage of p21/WAF1 expression demonstrates. These observations are a proof of concept for a more selective therapy, based on the combination of CDK4/6 inhibition and radiotherapy, which would only benefit to those patients with a functional p53 pathway.

Blockage of autophagic flux is associated with lymphocytosis and higher percentage of tumoral cells in chronic lymphocytic leukemia of B cells.

PURPOSE: Autophagy has lately emerged as an important biological process with implications in several hematological pathologies. Recently, a growing body of evidence supports a putative role of autophagy in chronic lymphocytic leukemia; however, no definitive clue has been established so far. To elucidate this issue, we have developed a pilot study to measure autophagic flux in peripheral blood mononuclear cells from chronic lymphocytic leukemia patients, and explored its correlation with classical clinical/analytical parameters. METHODS/PATIENTS: Thirty-three chronic lymphocytic leukemia patients participated in the study. Autophagic flux in peripheral blood mononuclear cells was determined by western blot measuring the levels of the proteins p62 and lipidated LC3. Moreover, p62 mRNA levels were analyzed by RT-qPCR. RESULTS: Lymphocytosis and the percentage of tumoral lymphocytes in chronic lymphocytic leukemia patients statistically correlate with a blocked autophagic flux. CONCLUSION: Alterations in autophagic flux could play an important role in the physiopathology of chronic lymphocytic leukemia.

New VMD2 gene mutations identified in patients affected by Best vitelliform macular dystrophy.

PURPOSE: The mutations responsible for Best vitelliform macular dystrophy (BVMD) are found in a gene called VMD2. The VMD2 gene encodes a transmembrane protein named bestrophin-1 (hBest1) which is a Ca(2+)-sensitive chloride channel. This study was performed to identify disease-specific mutations in 27 patients with BVMD. Because this disease is characterised by an alteration in Cl(-) channel function, patch clamp analysis was used to test the hypothesis that one of the VMD2 mutated variants causes the disease. METHODS: Direct sequencing analysis of the 11 VMD2 exons was performed to detect new abnormal sequences. The mutant of hBest1 was expressed in HEK-293 cells and the associated Cl(-) current was examined using whole-cell patch clamp analysis. RESULTS: Six new VMD2 mutations were identified, located exclusively in exons four, six and eight. One of these mutations (Q293H) was particularly severe. Patch clamp analysis of human embryonic kidney cells expressing the Q293H mutant showed that this mutant channel is non-functional. Furthermore, the Q293H mutant inhibited the function of wild-type bestrophin-1 channels in a dominant negative manner. CONCLUSIONS: This study provides further support for the idea that mutations in VMD2 are a necessary factor for Best disease. However, because variable expressivity of VMD2 was observed in a family with the Q293H mutation, it is also clear that a disease-linked mutation in VMD2 is not sufficient to produce BVMD. The finding that the Q293H mutant does not form functional channels in the membrane could be explained either by disruption of channel conductance or gating mechanisms or by improper trafficking of the protein to the plasma membrane.

Assessment of a press-fit proximal femoral modular reconstruction implant (PFMR®) at 14.5 years. A 48-case series with a disturbing rate of implant fracture.

INTRODUCTION: The PFMR® proximal femoral modular reconstruction implant (Protek, Sulzer Orthopedics, Switzerland) is a straight modular stem in sanded titanium with press-fit anchorage, intended to achieve spontaneous bone reconstruction following Wagner's principle. The aim of the present study was to analyze long-term clinical and radiological outcome. MATERIAL AND METHOD: A single-center retrospective study included 48 PFMR stems implanted in 47 patients between 1998 and 2002. Results in this series were previously reported at 7 years' follow-up. Clinical assessment used PMA and Harris scores. Radiologic assessment focused on stem stability and osseointegration, and bone stock following Le Béguec. RESULTS: Twenty-three patients were seen at a mean 14.5 years' follow-up (13 deceased, 11 lost to follow-up), including 1 with bilateral implants, i.e., 24 stems. PMA and Harris scores, stem stability and osseointegration and bone stock were stable with respect to the 7-year findings. Radiology found 7 stem fractures in the Morse taper, i.e., in 29% of implants. Two of these cases required femoral implant replacement; 5 were asymptomatic. DISCUSSION AND CONCLUSION: Long-term outcome for PFMR stems was clinically and radiologically satisfactory for the 16 patients free of mechanical complications. The Morse taper fracture rate was high, and higher than reported elsewhere. The usual risk factors for implant fracture were not found in the present series. The modular design of the press-fit revision implant is its weak point; monoblock implants should be used in patients with good life-expectancy. LEVEL OF EVIDENCE: IV (retrospective study).

Nutritional optic neuropathies.

Nutritional deficiency may be the cause of a genuine optic neuropathy, sometimes associated with involvement of the peripheral nervous system. Nutritional optic neuropathies are usually bilateral, painless, chronic, insidious and slowly progressive. Most often, they present as a non-specific retrobulbar optic neuropathy. The differential diagnosis with other causes of optic nerve involvement, in particular of toxic origin, may be particularly difficult. Nutritional deficits are often associated with toxic effects from alcohol and tobacco; therefore, the separation of the nutritional and toxic components is often illusory and artificial. The pathophysiological mechanisms involved in nutritional -- and toxic -- optic neuropathies affect biochemical pathways involved in cell energetic production, correction of oxidative stress and quenching of free radicals. The recognition of these mechanisms could provide future therapeutic alternatives. Currently, the treatment is limited to the intensive use of vitamins with variable results in individual cases, and to the implementation of preventive measures, when feasible.

[Pediatric aspects of Fabry's disease]. / Aspects pédiatriques de la maladie de Fabry.

Fabry's disease is a rare X-linked inborn error of glycosphingolipid metabolism characterised by an abnormal lipid storage due to a defect of lysozomal alphagalactosidase. The consequence is a storage of glycosphingolipides in all tissues. This storage in vessels's endothelial cells is responsible, in males, for severe ischemic lesions leading to progressive kidney failure, cardiac and cerebral dysfunctions. Similarly, it involves ocular tissues, mainly the cornea, the conjunctiva and the lens. The corneal storage, known as cornea verticillata, is a clinical marker easy to recognize by slit lamp examination of the affected males and carrier females. The enzymatic activity of alphagalactosidase is reduced in tears. Characteristic lamellar bodies can be observed by electron microscopy study of a conjunctival biopsy. Until recently, treatment was limited to symptomatic management of pain, and end-stage complications of renal failure, cardiac or brain disease. Recent studies have demonstrated that enzyme replacement therapy by genetic engineering is now shown to be promising for affected patients.

[Painful ophthalmoplegia in children: Tolosa-Hunt syndrome or ophthalmoplegic migraine?]. / Les ophtalmoplégies douloureuses de l'enfant: place du syndrome de Tolosa-Hunt et de la migraine ophtalmoplégique.

In children with painful ophthalmoplegia, the diagnosis of Tolosa-Hunt syndrome or of ophthalmoplegic migraine should only be considered when tumoral, infectious, inflammatory or vascular causes have been excluded by appropriate investigations. Both entities are classified as "neuralgia" by the International Headache Society, and seem to share a similar pathogenic mechanism. Both diseases have many clinical similarities with slight differences concerning pain characteristics or ocular associated symptoms. High resolution CT scan or contrast enhanced MRI can be necessary to exclude other causes of painful ophthalmoplegia. They can sometimes objectify an inflammatory process of the cavernous sinus in Tolosa-Hunt syndrome or a reversible enhancement and thickening of the cisternal segment of the oculomotor nerve during an ophthalmoplegic migraine. Pain and ophthalmoplegia quickly resolve with corticosteroids. Such treatment may decrease the risk of recurrence. It is important to follow-up these patients for a 2 years period and to repeat the etiologic assessment. We report here 2 cases of children with painful ophtalmoplegia.

[Arthroscopic treatment of capsular shoulder stiffness]. / Traitement arthroscopique des raideurs capsulaires de l'épaule.

The shoulder capsular sitffness must be managed first by a physiotherapist and the arthroscopic release is indicated after failure. The clinical assessment is essential and reveals the loss of passive motion in specified direction. The x-rays and imaging are necessary for excluding the other etiologies of shoulder stiffness. The arthroscopic treatment is part of he treatment strategy which has to be explained to the patient. The arthroscopic treatment starts by measuring under anesthesia the loss of passive motion. The next step consists of the release of the rotator interval followed by resection of the anterior capsule. Finally, the posterior capsule is cut according to the location of the capsular retraction. The interest of the subacromial debridement is still of debate. The postoperative pain control and the rehabilitation are part of the treatment. The literature analysis demonstrates the efficiency of the arthroscopic treatment, even if the post-op care are often long. A delay of 6 months is currently necessary to obtain the final results. The main advantages of the arthroscopic treatment is to address specifically the retracted capsule and to perform a selective release which allow to start rehabilitation program early.

Slow-moving and far-travelled dense pyroclastic flows during the Peach Spring super-eruption.

Explosive volcanic super-eruptions of several hundred cubic kilometres or more generate long run-out pyroclastic density currents the dynamics of which are poorly understood and controversial. Deposits of one such event in the southwestern USA, the 18.8 Ma Peach Spring Tuff, were formed by pyroclastic flows that travelled >170 km from the eruptive centre and entrained blocks up to ∼ 70-90 cm diameter from the substrates along the flow paths. Here we combine these data with new experimental results to show that the flow's base had high-particle concentration and relatively modest speeds of ∼ 5-20 m s(-1), fed by an eruption discharging magma at rates up to ∼ 10(7)-10(8) m(3) s(-1) for a minimum of 2.5-10 h. We conclude that sustained high-eruption discharge and long-lived high-pore pressure in dense granular dispersion can be more important than large initial velocity and turbulent transport with dilute suspension in promoting long pyroclastic flow distance.

Two-stage total hip arthroplasty for complex pelvic abnormalities: Example of hip arthrodesis conversion with concomitant treatment of pelvic and acetabular non-union.

Hip prosthesis implantation requires a stable pelvic foundation, which may be lacking in patients with complex pelvic abnormalities (e.g., arthrodesis conversion, tumour excision, or revision with large bony defects). Many reconstructive options exist for these situations, but their outcomes vary with the initial amount of bone loss and with the technique used. We describe a two-stage arthroplasty technique (acetabular cup first, then femoral stem) and report its use in a case of arthrodesis conversion with concomitant treatment of pelvic and acetabular non-union. Clinical and radiological outcomes after 5 years are reported. This procedure can be adapted to the most complex cases of pelvic reconstruction.

Influence of fixation with two vs. three screws on union of arthroscopic tibio-talar arthrodesis: Comparative radiographic study of 111 cases.

BACKGROUND: Ankle arthrodesis is a treatment of choice for advanced tibio-talar disease unresponsive to conservative treatment. Using arthroscopy to perform this procedure minimises soft-tissue trauma while providing similar outcomes to those of open surgery. Union rates have ranged across studies from 85% to 100%. The objective of this study was to assess the potential influence on union of the number of screws used for arthrodesis fixation. HYPOTHESIS: The working hypothesis was that using three screws for arthrodesis produced a higher union rate than did using only two screws. MATERIAL AND METHODS: This single-centre retrospective comparative study included 111 cases of arthroscopic ankle arthrodesis (in 108 patients) carried out between February 1994 and October 2012. The number of screws was two in 75 cases and three in 36 cases. Union was assessed on radiographs taken 2, 6, and 12months postoperatively. RESULTS: Mean age at surgery was 55.8years. After 12months, union was achieved in 87.4% cases overall. The non-union rate was 16% with two screws and 5.6% with three screws. Three-screw fixation was associated with a significantly higher rate of union of the medial gutter after 6months and of the lateral gutter after 12months. DISCUSSION: Our findings support the use of three screws for fixation of arthroscopic tibio-talar arthrodesis. Adding a third screw seems associated with a lower risk of non-union and a shorter time to union. These effects can be ascribed to greater stability of the construct. LEVEL OF EVIDENCE: Level IV, retrospective study.

Developments in imaging methods used in hip arthroplasty: A diagnostic algorithm.

BACKGROUND: Several imaging modalities can be used to diagnose complications of hip prosthesis placement. Despite progress in these imaging techniques, there are, as yet, no guidelines as to their respective indications. METHODS: We formed a panel of experts in fields related to prosthesis imaging (radiology, nuclear medicine, orthopedic surgery) and conducted a review of the literature to determine the value of each modality for diagnosing complications following hip replacement. RESULTS: Few recent studies have investigated the benefits related to the use of the latest technical developments, and studies comparing different methods are extremely rare. CONCLUSIONS: We have developed a diagnostic tree based on the characteristics of each imaging technique and recommend its use. Computed topography was found to be the most versatile and cost-effective imaging solution and therefore a key tool for diagnosing the complications of hip replacement surgery.

[Computer-assisted diagnosis and therapy for glaucoma]. / Diagnostic et traitement des glaucomes.

Boolean algebra, or combinatory analysis and their related computer routines, can provide invaluable help in resolving classic diagnostic problems. However complex each case may be, the diagnosis is always made from a finite set of data, and the fundamental problem is thus how to exploit this data. Invention no longer has a place in ascertaining a diagnosis. Traditional ways of reasoning are numerous, personal, and fragile, but fortunately redundant. They may give rise to four types of error: omission or mistake (an error of judgment), either during the semiotic or the dialectic stages. Whereas the physiological capacity of the human brain and memory only enables it to make a limited number of hypotheses concerning certain aspects of glaucoma, computer programs can take the total number of hypotheses into account, i.e., 3000. For every input the program explores each of the 3,000 items, thus eliminating the four types of error. The probabilistic nature of data, which compromises the confidence one can have in conclusions resulting from such complex reasoning, is treated by the adjusted probabilities. The use of such diagnostic aids, whose thesaurus is updated regularly, is reserved for ophthalmologists, the only authority capable of assessing the pertinence of the computer responses. Consequently, the specialist can rest assured that the patient has benefited from the most comprehensive and updated knowledge in medical science.