Risk assessment of personnel exposure in a central cytotoxic preparation unit using the FMECA method.

INTRODUCTION: Personnel involved in the preparation of cytotoxics are exposed to them and the resulting risks. To protect themselves, many means of protection are currently implemented. Nevertheless, the exposure of these manipulators remains a possibility to be considered. MATERIALS AND METHODS: The study was conducted during the period (October-November 2022) in the pharmacy of the National Institute of Oncology (INO), a hospital structure specializing in cancer care. The Failure Mode, Effects and Criticality Analysis method was used to assess the risks of exposure of personnel in a central cytotoxic preparation unit and then calculate the criticality index (CI = severity × frequency × detectability). The risks were classified into toxic, traumatic, chemical, and environmental risks. We have cited 12 failure modes of which nine are minor and three are major. The three major modes cited are essentially related to the particulate environment, direct contact and daily passive inhalation of handling. CONCLUSION: Our study shows that in our institution, the analysis of the risk of exposure of personnel to cytotoxics remains important, hence the interest of automaton in charge of preparations and which will gradually take charge of all the preparations. The existing procedures and the pharmacotechnical equipment used also contribute to protection and risk reduction.

Retrospective analysis of failures of ambulatory elastomeric pumps containing 5-FU in a hospital pharmacy unit.

INTRODUCTION: Ambulatory chemotherapy is an important and major advance in clinical oncology practice since it allows the administration of chemotherapy in the comfort of the patient's home without the assistance of a health professional by means of an elastomeric pump. However, these pumps are not without risks and can be the cause of incidents due to technical failures. Our objective is to study the technical failures of elastomeric pumps in the Cytotoxic Preparation Unit and in the patient's home, to evaluate the possible impact of these failures on the patient and on the staff and to propose measures to reduce them. MATERIALS AND METHODS: This is a retrospective study conducted at the pharmacy of the National Institute of Oncology in Rabat. It gathered all the specific reports on elastomeric pumps issued during the period (January 2017-May 2021) by the cytotoxic preparation unit to the materiovigilance cell via a notification form. RESULTS: 205 cases of elastomeric pump materialovigilance were identified during the study period. The main technical failures were: chemotherapy product leakage (44%), flow rate anomalies (30%) and injection difficulties (20%). Following these incidents, certain actions were undertaken such as alerts sent to the supplier and letters sent to the competent health authorities. CONCLUSION: Despite the failures that may have occurred, elastomeric pumps have revolutionized home chemotherapy delivery. They are considered reliable, consistent, easy to use and handle, and are well accepted in the population.

Adaptive finite element simulation of fretting wear and fatigue in a taper junction of modular hip prosthesis.

Modular taper junctions are commonly used in total hip arthroplasty to offer a wide range of intraoperative choices to surgeons. The damage at the taper surfaces can lead to the implant failure either by material removal (wear) or by cracks nucleation (fatigue). This paper presents a methodology based on the finite element approach to study both fretting wear and fatigue, taking into account their interaction in the modular taper. The modified Archard's law was employed to compute wear depth and the corresponding volume loss while the fatigue life was predicted using two critical plane fatigue parameters (Smith-Watson-Topper and Fatemi-Socie). An adaptive meshing technique was implemented to take into account the geometry changes and the material removal effect on fatigue life. The methodology developed was discussed and validated against available experimental data from the literature. In this case considered, a transition from a partial slip regime to a large slip one, which is mainly controlled by the contact slip amplitude, was found to reduce the fatigue life and a critical slip value was identified. This provides an efficient tool for an in-depth understanding of fretting in taper junctions and for future design.

Large field-of-view phase and fluorescence mesoscope with microscopic resolution.

Phase and fluorescence are complementary contrasts that are commonly used in biology. However, the coupling of these two modalities is traditionally limited to high magnification and complex imaging systems. For statistical studies of biological populations, a large field-of-view is required. We describe a 30 mm2 field-of-view dual-modality mesoscope with a 4-µm resolution. The potential of the system to address biological questions is illustrated on white blood cell numeration in whole blood and multiwavelength imaging of the human osteosarcoma (U2-OS) cells.

Hemolysis by surfactants--A review.

An overview of the use of surfactants for erythrocyte lysis and their cell membrane action mechanisms is given. Erythrocyte membrane characteristics and its association with the cell cytoskeleton are presented in order to complete understanding of the erythrocyte membrane distortion. Cell homeostasis disturbances caused by surfactants might induce changes starting from shape modification to cell lysis. Two main mechanisms are hypothesized in literature which are osmotic lysis and lysis by solubilization even if the boundary between them is not clearly defined. Another specific mechanism based on the formation of membrane pores is suggested in the particular case of saponins. The lytic potency of a surfactant is related to its affinity for the membrane and the modification of the lipid membrane curvature. This is to be related to the surfactant shape defined by its hydrophobic and hydrophilic moieties but also by experimental conditions. As a consequence, prediction of the hemolytic potency of a given surfactant is challenging. Several studies are focused on the relation between surfactant erythrolytic potency and their physico-chemical parameters such as the critical micellar concentration (CMC), the hydrophile-lipophile balance (HLB), the surfactant membrane/water partition coefficient (K) or the packing parameter (P). The CMC is one of the most important factors considered even if a lytic activity cut-off effect points out that the only consideration of CMC not enough predictive. The relation K.CMC must be considered in addition to the CMC to predict the surfactant lytic capacity within the same family of non ionic surfactant. Those surfactant structure/lytic activity studies demonstrate the requirement to take into account a combination of physico-chemical parameters to understand and foresee surfactant lytic potency.

ISAR Imaging of Maneuvering Targets Based on the Modified Discrete Polynomial-Phase Transform.

Inverse synthetic aperture radar (ISAR) imaging of a maneuvering target is a challenging task in the field of radar signal processing. The azimuth echo can be characterized as a multi-component polynomial phase signal (PPS) after the translational compensation, and the high quality ISAR images can be obtained by the parameters estimation of it combined with the Range-Instantaneous-Doppler (RID) technique. In this paper, a novel parameters estimation algorithm of the multi-component PPS with order three (cubic phase signal-CPS) based on the modified discrete polynomial-phase transform (MDPT) is proposed, and the corresponding new ISAR imaging algorithm is presented consequently. This algorithm is efficient and accurate to generate a focused ISAR image, and the results of real data demonstrate the effectiveness of it.

Ganser-like syndrome after loss of psychic self-activation syndrome: psychogenic or organic?

Very few data are available on the long-term changes in the cognitive abilities of patients with loss of psychic self-activation syndrome (LPSAS). Here, we present a 25-year follow-up study on a case of LPSAS resulting from bilateral pallidal lesions caused by carbon monoxide intoxication. Typical signs of LPSAS were observed, showing no changes in severity, but Ganser syndrome (GS) gradually developed and worsened during the follow-up period. GS is generally assumed to be a psychogenic syndrome, but an organic etiology has been suspected by the authors of several case reports. Here, atypical features of GS plead against the independence of GS and LPSAS. DaTSCAN and brain 18FDG-PET were performed. Since left hippocampal hypometabolism has been previously described in patients with functional amnesia, it is possible that long periods of mental inactivity may have psychological consequences, but the atypical features of GS also suggest that an organic mechanism may be involved.

A low cost and high throughput magnetic bead-based immuno-agglutination assay in confined droplets.

Although passive immuno-agglutination assays consist of one step and simple procedures, they are usually not adapted for high throughput analyses and they require expensive and bulky equipment for quantitation steps. Here we demonstrate a low cost, multimodal and high throughput immuno-agglutination assay that relies on a combination of magnetic beads (MBs), droplets microfluidics and magnetic tweezers. Antibody coated MBs were used as a capture support in the homogeneous phase. Following the immune interaction, water in oil droplets containing MBs and analytes were generated and transported in Teflon tubing. When passing in between magnetic tweezers, the MBs contained in the droplets were magnetically confined in order to enhance the agglutination rate and kinetics. When releasing the magnetic field, the internal recirculation flows in the droplet induce shear forces that favor MBs redispersion. In the presence of the analyte, the system preserves specific interactions and MBs stay in the aggregated state while in the case of a non-specific analyte, redispersion of particles occurs. The analyte quantitation procedure relies on the MBs redispersion rate within the droplet. The influence of different parameters such as magnetic field intensity, flow rate and MBs concentration on the agglutination performances have been investigated and optimized. Although the immuno-agglutination assay described in this work may not compete with enzyme linked immunosorbent assay (ELISA) in terms of sensitivity, it offers major advantages regarding the reagents consumption (analysis is performed in sub microliter droplet) and the platform cost that yields to very cheap analyses. Moreover the fully automated analysis procedure provides reproducible analyses with throughput well above those of existing technologies. We demonstrated the detection of biotinylated phosphatase alkaline in 100 nL sample volumes with an analysis rate of 300 assays per hour and a limit of detection of 100 pM.

Motor evoked potentials in clinically isolated syndrome suggestive of multiple sclerosis.

The aim of the present study was to determine the sensitivity and the profile of motor evoked potentials (MEP) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). We measured the central motor conduction time (CMCT), amplitude ratio (AR), and surface ratio (SR) in tibialis anterior and first dorsal interosseous muscles in 22 patients with CIS. In 12 patients, the triple stimulation technique (TST) was also performed. AR was abnormal in 50% of patients, CMCT in 18% of patients, and TST in 25% of patients. AR had the highest sub-clinical sensitivity and the best positive predictive value. In the absence of clinical pyramidal signs, an early AR decrease seems to result from demyelination inducing excessive temporal dispersion of the MEP, while in territories with clinical pyramidal signs, it seems to result from conduction failure, which suggests that clinical pyramidal signs may be attributable to conduction failure. This study demonstrates that MEP, especially the AR, is sensitive to motor pathway dysfunction right from the early stages of MS.

[Esophageal achalasia, sleep disorders and chorea in a tauopathy without ophthalmoplegia, parkinsonian syndrome, nor dementia (progressive supranuclear palsy?): clinicopathological study]. / Achalasie de l'aesophage, troubles du sommeil et mouvements choréiques au cours d'une taupathie sans ophtalmoplégie, syndrome parkinsonien ni démence (paralysie supranucléaire progressive?): étude clinicopathologique.

CONTEXT: Progressive supranuclear palsy (PSP) is classically characterized by supranuclear ophthalmoplegia, paroxysmal imbalance with backward falling, axial dystonia, rigidity, pseudobulbar palsy and cognitive dysfunction. However, incomplete or atypical clinical presentation has been previously reported, but in all these cases, the patients had at least one of the main clinical features of the disease (ophthalmoplegia, parkinsonian syndrome or cognitive dysfunction). CASE REPORT: A 60-year-old woman presented with nocturnal agitation and choreiform movements. A few months later she developed severe swallowing disorders, caused by achalasia of the upper esophageal sphincter, and responsible for recurrent acute respiratory distress and pneumonia, prevailing to tracheotomy and gastrostomy. She died suddenly two years after the onset of the symptoms. RESULTS: Postmortem examination of brain revealed a tauopathy, with deposition of abnormal phosphorylated tau in threads and in coiled-shaped as well as globose tangles in the brainstem, subthalamic nuclei and hippocampus. Nuclei of the medulla, including the vagus/solitarius complex and the region of the nucleus ambiguous were especially rich in tau positive inclusions. Ultrastructural analysis of globoid-shaped tangles in the brainstem revealed the presence of straight and paired helicoidal filaments compatible with a PSP. CONCLUSIONS: This case contributes to improve knowledge of the clinical phenotypic range of PSP. In this case, the neuropathological lesions accounted for most of the symptoms. However, the early death of the patient was probably related to the particular distribution of the neuropathological lesions. This case suggests that the initial neuropathological changes in PSP is located in the dorsal brainstem.

Intact subliminal processing and delayed conscious access in multiple sclerosis.

Periventricular white matter damage affecting large bundles connecting distant cortical areas may constitute the main neuronal mechanism for the deficit of controlled information processing observed in patients with early multiple sclerosis (MS). Visual backward masking has been demonstrated to affect late stages of conscious perception involving long-range interactions between visual perceptual areas and higher level integrative cortices while leaving intact early feed-forward visual processing and even complex processing such as object recognition or semantic processing. We therefore hypothesized that patients with early MS would have an elevated masking threshold, because of an impairment of conscious perception whereas subliminal processing of masked stimuli would be preserved. Twenty-two patients with early MS and 22 normal controls performed two backward-masking experiments. We used Arabic digits as stimuli and varied quasi-continuously the temporal interval with a subsequent mask, thus allowing us to progressively "unmask" the stimuli. We finely quantified the visibility of the masked stimuli using both objective and subjective measures, thus obtaining accurate estimates of the threshold duration for access to consciousness. We also studied the priming effect caused by the variably masked numbers on a comparison task performed on a subsequently presented and highly visible target number. The threshold for access to consciousness of masked stimuli was elevated in MS patients compared to controls, whereas non-conscious processing of these stimuli, as measured by priming, was preserved. These findings suggest that conscious access to masked stimuli depends on the integrity of large-scale cortical integrative processes, which involve long-distance white matter projections, and are impaired due to diffuse demyelinating injury in patients with early MS.

[Brain magnetic resonance imaging and neuropathology of cortical laminar necrosis]. / Nécrose laminaire corticale: aspects en imagerie par résonance magnétique et étude anatomoclinique.

INTRODUCTION: The most frequent acute and sub-acute complications of chronic alcoholism are delirium tremens, hepatic encephalopathy and Gayet-Wernicke encephalopathy. Morel laminar sclerosis is a rare and less known complication, often reported with Marchiafava-Bignami disease. CASE REPORT: A 57-year-old alcoholic man presented delirium after surgery. Anterograde and retrograde amnesia as well as wrong recognitions appeared progressively and one generalized seizure occurred. He then developed mutism and became bedridden. Magnetic resonance imaging (MRI) showed high-intensity bilateral temporoparietal signals from white matter on T2-weighted images and high-intensity signals from the parietal cortex on T1-weighted images. The patient died four months after the onset of the delirium. Post-mortem examination of the brain showed cortical laminar necrosis with Alzheimer Type II gliosis but without demyelinisation of the corpus callosum. CONCLUSION: Cortical laminar necrosis with chronic ethylism is usually called Morel's laminar sclerosis. Nevertheless, histology is not typical of this diagnosis, because of necrosis especially of the second (and not the third) layer of the cortex, and because of the absence of lesion of the corpus callosum. MRI data are of interest here because they were rarely reported in cases of Morel's laminar sclerosis.

Prospective clinical and electrophysiological follow-up on a multiple sclerosis population treated with interferon beta-1 a: a pilot study.

OBJECTIVE: To analyse transcranial magnetic stimulation (TMS) variables in a prospective six-month follow-up pilot study on patients suffering from relapsing-remitting multiple sclerosis (RRMS), satisfying inclusion criteria for interferon (IFN) beta-1a treatment. BACKGROUND: So far, no predictive factors are available as to the course of RRMS treated with IFN beta-1 a. DESIGN/METHODS: Fifteen RRMS patients were studied before (month 0 (M0)) and after IFN beta-1a onset (M3, M6). The parameters analysed were motor functional score (mFS), Expanded Disability Status Scale (EDSS), and TMS variables - central motor conduction time (CMCT) and amplitude ratio (AR). RESULTS: Four of the six patients with no motor signs at inclusion, subsequently showed signs of pyramidal dysfunction. All had abnormal M0_TMS variables. The number of M0_TMS abnormalities per patient was greatest in the group that showed mFS worsening, and was significantly correlated with M6_EDSS. The M0_CMCT was significantly correlated with M6_EDSS. During follow-up, the number of patients with abnormal TMS variables decreased from 12/15 to 4/15, and the total number of abnormalities decreased from 33.3 to 16.7%. CONCLUSIONS: TMS variables might be predictive of disease progression. The improvement observed here in the TMS variables may reflect an improvement in MS patients undergoing IFN beta treatment.

Relationships between gray matter metabolic abnormalities and white matter inflammation in patients at the very early stage of MS : a MRSI study.

Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) was used to study metabolic abnormalities inside the gray matter (GM) during or distant to white matter (WM) inflammatory processes reflected by T(1) gadolinium-enhancing lesions in patients at the very early stage of multiple sclerosis (MS). The spectroscopic examination was performed in the axial plane using a home-designed acquisition-weighted, hamming shape, 2D-SE pulse sequence (TE = 135 ms; TR = 1,600 ms). Bilateral thalami and the medial occipital cortex were explored in 35 patients (15 with and 20 without T(1)-Gd enhancing lesions) with clinically isolated syndrome suggestive of MS and in 30 controls. The mean duration since the first presenting symptom was 9.1 (+/-6.7) months. The two groups of patients (with or without T(1) Gd-enhancing lesions) did not differ in terms of time elapsed since the first clinical onset and T(2) lesion load. The spatial contamination of surrounding WM tissues was obtained in each GM region by determining the tissue component in the ROI from GM and WM probability maps smoothed with the point spread function of the MRSI acquisition. Contribution of WM signal was important (60%) inside thalami while the region centered on the medial occipital cortex was well representative of GM metabolism (>70%). Comparisons of relative metabolite levels (ratios of each metabolite over the sum of all metabolites) between all patients and controls showed significant decrease in relative N-acetyl aspartate (NAA) levels, increase in relative choline-containing compounds (Cho) levels and no change in relative creatine/phosphocreatine levels inside the three ROIs. Decrease in relative NAA levels and increase in relative Cho levels were found in patients with inflammatory activity, while no metabolic alterations were present in patients without T(1) Gd-enhancing lesions. These results suggest that abnormalities in GM metabolism observed in patients at the very early stage of MS are mainly related to neuronal dysfunction occurring during acute inflammatory processes.

Onset and underpinnings of white matter atrophy at the very early stage of multiple sclerosis--a two-year longitudinal MRI/MRSI study of corpus callosum.

BACKGROUND: Atrophy of corpus callosum (CC), a white matter structure linking the two hemispheres, is commonly observed in multiple sclerosis (MS). However, the occurrence and processes leading to this alteration are not yet determined. GOAL AND METHODS: To better characterize the onset and progression of CC atrophy from the early stage of MS, we performed a two-year follow-up magnetic resonance imaging/magnetic resonance spectroscopic imaging (MRI/MRSI) exploration of CC in 24 patients with clinically isolated syndrome. These patients were explored using the same protocol at month (M)6, M12 and M24. MRI/MRSI techniques were applied to measure CC volume, and relative concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr) and choline-containing compounds (Cho). A group of matched controls was also explored. RESULTS: Atrophy of CC, not present at baseline, was observed at M12 and progressed over the second year (M24). At baseline, a decrease in relative NAA level was observed in the anterior and posterior body of CC, with normalization during the follow-up period. In the anterior body, an increase in relative Cho level was observed, with normalization at M6. Normal relative Cr levels were observed at all time points in all sub-regions. The rate of CC atrophy was correlated with the change in the Expanded Disability Status Scale (EDSS) during the follow-up period. CONCLUSION: These results suggest that CC atrophy appears over a period of one year after the first acute inflammatory episode, and that this atrophy is accompanied, especially in the anterior body of CC, by a normalization of the relative Cho levels, marker of acute inflammation, and NAA levels, marker of neuronal dysfunction and/or loss.

[Analysis of antibiotics as a curative measure in four hospital units]. / Analyse de la prescription antibiotique a visee curative en milieu chirurgical et en reanimation.

In order to analyse the methods of curative prescription of antibiotics in four units of hospitalization of the hospital Charles Nicolle of Tunis, a descriptive study of prescriptions was carried out during the first five months of year 2001. On the whole, 165 prescriptions delivered to patients were included in the study. The average age of the patients was 44 years, the sex ratio of 1.45 and the average duration of 15.1 days. Approximately two thirds of the initially probabilist prescriptions were not documented secondarily. Those secondarily documented (n = 51) were essentially related to nosocomial pneumonias and septicaemias (29 and 10 prescriptions). The two germs most frequently isolated during nosocomial pneumonias were Acinetobacter baumannii and, Pseudomonas aeruginosa (17 and 8 strains). Only imipenem, netilmicin and colistin remain active on A. baumannii. The bitherapy was the most used treatment (87.5%). It was generally an association beta-lactamin-aminosid (52.9%). The average cost of a documented prescription varied from 943,6 to 1184,9 TD (Tunisian Dinars) according as the prescription were secondarily documented or not.

[Multiple strokes after chickenpox primo-infection in an adult]. / Accidents vasculaires cérébraux multiples et primo-infection varicelleuse chez un adulte.

INTRODUCTION: Chickenpox is considered as a high risk factor for developing stroke in childhood, but descriptions in adult are exceptional (only three cases reported, to our knowledge). CASE REPORT: A 37-year-old man presented with a chickenpox eruption, followed by a right parietal and a left occipital infarcts, associated with multiple lacunae. There was no coagulation disorder, no hypertension or cardiovascular disorder. Cerebral angiography showed an irregular narrowing of the right internal parietal artery and vascular defects in right parietal and left occipital areas. The diagnosis of VZV-related vasculitis was evoked. White cell count, serology and VZV PCR were negative in the cerebrospinal fluid. Clinical improvement was observed after treatment by corticosteroids and aciclovir. CONCLUSION: Chickenpox is a rare cause of cerebral vasculitis. Involvement of both medium and small vessels was present here, contrary to other adult case reports in the literature. Hematogenous dissemination of the virus responsible for cerebral vasculitis seems to be the most probable pathophysiological mechanism.

[Acute tetraparesis of cerebral origin]. / Tétraparésie aiguë d'origine cérébrale.

INTRODUCTION: Thrombolytic treatment in the early stage of ischemic cerebral attacks requires rapid confirmation of the diagnosis and topographic localization. Unusual clinical features can lead to misdiagnosis with the risk of delaying optimal therapeutic management. OBSERVATION: We report the cases of two patients who experienced acute tetraparesis without any associated encephalic sign, consistent with the diagnosis of spinal cord injury. Cervical magnetic resonance imaging (MRI) was normal. Conversely, cerebral MRI displayed in both cases bilateral hemispheric infarction. Two ischemic lesions were revealed in the territory of both anterior cerebral arteries in the first patient, while the second patient had a bilateral infarction in the posterior arms of both internal capsules. CONCLUSION: In case of tetraparesis, emergency spinal cord MRI should be performed to rule out neurosurgical etiologies and ischemia. If negative, cerebral MRI should be performed at the same time to look for early cerebral infarction in both hemispheres and determine the indication for thrombolysis.