Generic vancomycin products: Analysis of serum concentrations in patients with acute myeloid leukemia.

UNLABELLED: Concerns have recently emerged about the quality of generic vancomycin products. Our aim is to analyze serum vancomycin concentrations measured 48 hours after the start of an empirical treatment regimen in patients with acute myeloid leukemia (AML) who received one of the two generic vancomycin products available in France. PATIENTS AND METHODS: Seventy-nine AML patients treated with vancomycin during two study periods were included in the study. Our vancomycin dosing regimen was based on the patients' total body weight adjusted for renal clearance. RESULTS: A total of 93 serum vancomycin concentrations were collected: 31 in period 1 and 62 in period 2. In bivariate analysis, the mean serum vancomycin concentrations were not significantly different (19.9 ± 11.2 mg/L in period 1 vs 18.9 ± 6.0 mg/L in period 2, P=0.64). In the final generalized estimating equations model, serum vancomycin concentrations correlated statistically with a positive coefficient for age (P<0.001) and with negative coefficients for male sex (P=0.001) and hemoglobin level (P=0.021). CONCLUSION: Serum vancomycin concentrations measured 48 hours after the start of an empirical treatment were not influenced by the nature of the generic product but correlated with age, sex and hemoglobin level in AML patients.

Evaluating the safety of intraprocedural chest tube removal during medical thoracoscopy.

BACKGROUND: Medical Thoracoscopy (MT) is a diagnostic procedure during which after accessing the pleural space the patient's negative-pressure inspiratory efforts draw atmospheric air into the pleural cavity, which creates a space to work in. At the end of the procedure this air must be evacuated via a chest tube, which is typically removed in the post-anesthesia care unit (PACU). We hypothesized that its removal intra-operatively is safe and may lead to lesser post-operative pain in comparison to its removal in the PACU. METHODS: A retrospective review was conducted of all the MT with intraprocedural chest tube removal done between 2019 to 2023 in adult patients in a single center in New York, NY by interventional pulmonology. RESULTS: A total of 100 MT cases were identified in which the chest tube was removed intra-operatively. Seventy-seven percent of cases were performed as outpatient and all these patients were discharged on the same day. Post procedure ex-vacuo pneumothorax was present in 42% of cases. Sixty-five percent of cases had some post-procedure subcutaneous emphysema, none reported any complaint of this being painful, and no intervention was needed to relieve the air. Seventy-three percent required no additional analgesia in PACU. Of the 27% that required any form of analgesia, 59% required no additional analgesia beyond the first 24 h. CONCLUSIONS: Intraprocedural CT removal for MT is safe and may decrease utilization of additional analgesia post procedure. Further prospective studies are necessary to validate these conclusions.

Normal Saline Versus Hypertonic Saline for Airway STENT Maintenance: SALTY STENT Study.

BACKGROUND: Mucus plugging is a common complication of airway stenting. There is no data or guidance on the best airway hygiene regimen and consequently wide practice variation exists. METHODS: This single-center, nonblinded, randomized, pilot study aims to evaluate the effectiveness and safety of nebulized 3% saline (3%S) versus normal saline (NS) in reducing the incidence of mucus plugging in adult patients that undergo central airway stent placement. Patients were enrolled immediately after stent placement and randomized to nebulized 3%S or NS (3 mL) 3 times a day. Patients were scheduled for surveillance bronchoscopy in 4 to 6 weeks. Unscheduled bronchoscopies due to symptomatic mucus plugging were recorded. RESULTS: From December 2022 to March 2024, 37 patients were screened, and 35 were enrolled. Four in the 3%S and 8 in the NS group did not undergo a surveillance bronchoscopy and were excluded from the final analysis. During surveillance bronchoscopy for the 3%S (n=13) and NS (n=10) groups, obstructive mucus plugging was noted in 7.7% versus 40%, granulation requiring intervention in 7.7% versus 10%, and >25% circumferential biofilm in 0% versus 30%, respectively. In the 3%S versus NS groups, 0% versus 20% of patients required an unscheduled bronchoscopy due to mucus plugging. There were no side effects reported with the daily use of 3%S or NS. CONCLUSION: Nebulized 3%S is safe and may be equally or more effective than NS in preventing obstructive mucus plugging in patients who undergo airway stenting. A larger blinded randomized controlled trial is necessary to confirm this finding.

Airway stenting for liberation from positive pressure ventilation in patients with central airway obstruction presenting with acute respiratory failure.

BACKGROUND: Central airway obstruction (CAO) can lead to acute respiratory failure (RF) necessitating positive pressure ventilation (PPV). The efficacy of airway stenting to aid liberation from PPV in patients with severe acute RF has been scarcely published. We present a systematic review and our recent experience. METHODS: A systematic review of PubMed was performed, and a retrospective review of cases performed at our two institutions from 2018 to 2022 in adult patients who needed stent insertion for extrinsic or mixed CAO complicated by RF necessitating PPV. RESULTS: Fifteen studies were identified with a total of 156 patients. The weighted mean of successful liberation from PPV post-stenting was 84.5% and the median survival was 127.9 days. Our retrospective series included a total of 24 patients. The most common etiology was malignant CAO (83%). The types of PPV used included high-flow nasal cannula (HFNC) (21%), non-invasive ventilation (NIV) (17%) and Invasive Mechanical Ventilation (62%). The overall rate of successful liberation from PPV was 79%, with 55% of HFNC and NIV cases being liberated immediately post-procedure. The median survival of the patients with MCAO that were successfully liberated from PPV was 74 days (n = 16, range 3-893 days), and for those with that failed to be liberated from PPV, it was 22 days (n = 4, range 9-26 days). CONCLUSION: In patients presenting with acute RF from extrinsic or mixed morphology CAO requiring PPV, airway stenting can successfully liberate most from the PPV. This may allow patients to receive pathology-directed treatment and better end-of-life care.

Effect of interfaces on the melting of PEO confined in triblock PS-b-PEO-b-PS copolymers.

Block copolymers form nanostructures that have interesting physical properties because they combine, for a single compound, the complementary features brought by each block. However, in order to fully exploit these properties, the physical state of each kind of domain must be precisely controlled. In this work, triblock PS-b-PEO-b-PS copolymers consisting of a central poly(ethylene oxide) (PEO) block covalently bonded to polystyrene (PS) blocks were synthesized by Atom Transfer Radical Polymerization. Their morphology was investigated by X-ray scattering and TEM experiments whereas their thermodynamic behavior was characterized by DSC. A strong decrease of both the melting temperature and the degree of crystallinity of PEO, due to its confinement between the PS domains, was observed and analyzed with a modified Gibbs-Thomson equation, following the approaches used for fluids confined in porous media. The existence of an amorphous bound layer, a few nanometers thick, at the PEO/PS interface, that does not undergo any phase transition in the temperature range investigated, accounts for both the melting temperature depression and the decrease of crystallinity upon confinement. This interfacial layer may significantly affect the mechanical and transport properties of these block copolymers that find applications as solid polymer electrolytes in batteries for example. Moreover, the value obtained for the solid PEO/liquid PEO surface tension is lower than those previously published but is thermodynamically consistent with the surface tensions of polymers at the solid/vapor and liquid/vapor interfaces.

How risky is it to remove an airway stent?

BACKGROUND: Airway stent removal has traditionally been associated with a high complication rate. Most studies on stent removal are over a decade old, prior to newer anti-cancer therapies, and by including non-contemporary and uncovered metal stents, may not reflect the current practices. We review our experience at Mount Sinai Hospital to report outcomes of stent removal with more contemporary practices. METHODS: A retrospective review was carried out of all the airway stent removals performed between 2018 to 2022, in adult patients with benign or malignant airway diseases. Stents inserted and removal for stent trials for tracheobronchomalacia were excluded from the final analysis. RESULTS: Forty-three airway stents removals in 25 patients were included. Twenty-five (58%) stents were removed in 10 patients with benign diseases, and 18 (42%) stents were removed in the remaining 15 patients with malignant diseases. Patients with benign disease were more likely to have their stent removed (OR 3.88). 63% of the stents removed were silicone. The most common reasons for stent removal were migration (n = 14, 31.1%) and treatment response (n = 13, 28.9%). Rigid bronchoscopy was used in 86% of cases. Ninety-eight percent of removals were accomplished in a single procedure. The median time to removal of stents was 32.5 days. Three complications were noted: hemorrhage (n = 1, 2.3%) and stridor (n = 2, 4.6%); one not directly related to the stent removal. CONCLUSIONS: Covered metal or silicone airway stents, in the era of contemporary stents, better cancer-directed therapies and surveillance bronchoscopies, can be removed safely with the use of rigid bronchoscopy.

Characteristics of Systemic Sclerosis patients with positive anti-Th/To antibodies: About 6 patients and literature review.

Among the antibodies described in Systemic Sclerosis (SSc), anti-Th/To antibodies (anti-Th/To) are rare and have been poorly studied. Thus, little is known about the profile of anti-Th/To positive patients. From our local Biobank (Marseille, France), we retrospectively selected data for 6 patients positive for anti-Th/To with an Immunodot assay. All of them suffered from SSc, sharing clinical and biological common features such as a limited cutaneous form of SSc, a decreased lung diffusing capacity and a speckled nuclear nucleolar immunofluorescence pattern of antinuclear antibodies screening on HEp-2 cells. In order to further characterize patients positive for anti-Th/To, we performed a thorough literature review. From 402 studied patients positive for anti-Th/To, we confirmed that these antibodies are associated with the limited cutaneous form of the disease (88% of the patients), and with an SSc related-pulmonary involvement (50%). The review analysis pointed out the rarity of the anti-Th/To with an estimated mean frequency of 3.4% of all SSc patients worldwide, their usual exclusivity with respect to the specific antibodies of scleroderma, and their high specificity (around 98%) for the diagnosis of SSc.

Gram-scale purification of aconitine and identification of lappaconitine in Aconitum karacolicum.

Aconitum karacolicum from northern Kyrgyzstan (Alatau area) contains about 0.8-1% aconitine as well as other aconite derivatives that have already been identified. In this paper, we compare several methods for the further purification of an Aconitum karacolicum extract initially containing 80% of aconitine. Reverse-phase flash chromatography, reverse-phase semi-preparative HPLC, centrifugal partition chromatography (CPC) and recrystallization techniques were evaluated regarding first their efficiency to get the highest purity of aconitine (over 96%) and secondly their applicability in a semi-industrial scale purification process (in our case, 150g of plant extract). Even if the CPC technique shows the highest purification yield (63%), the recrystallization remains the method of choice to purify a large amount of aconitine as i) it can be easily carried out in safe conditions; ii) an aprotic solvent is used, avoiding aconitine degradation. Moreover, this study led us to the identification of lappaconitine in Aconitum karacolicum, a well-known alkaloid never found in this Aconitum species.

A clinical comparison of two formulations of tobramycin 0.3% eyedrops in the treatment of acute bacterial conjunctivitis.

PURPOSE: To compare the safety and efficacy of a new enhanced viscosity ophthalmic formulation of tobramycin, given twice daily (BID), with the existing four times daily (QID) treatment regimen in patients with acute bacterial conjunctivitis. METHODS: This was a 12-day, multicenter, observer-masked, randomized, parallel group study. Patients received one drop of tobramycin 0.3% (3 mg/mL) enhanced viscosity ophthalmic solution BID or tobramycin 0.3% (3 mg/mL) ophthalmic solution QID in the affected eyes for 7 days. The primary efficacy variable was the percentage of patients with sustained cure/presumed bacterial eradication based on clinical judgment at the test-of-cure visit (Day 12). Pretherapy bacterial isolates were obtained and tested for susceptibility to tobramycin by determination of minimum inhibitory concentrations (MIC). RESULTS: A total of 276 patients were enrolled in the study and 203 of these were culture positive and attended all follow-up examinations. In this group, 98% of those treated with tobramycin enhanced viscosity ophthalmic solution and 99% of those treated with tobramycin 0.3% ophthalmic solution were categorized as having sustained cure/presumed eradication at the test-of-cure visit (p = 0.6037). Reported adverse events were not serious, mild to moderate in severity, and generally did not prevent continuation in the study. Several pre treatment pathogens demonstrated tobramycin resistance (MIC > 4 mg/mL). However, therapy with both treatments was effective in the majority of the cases. CONCLUSIONS: Tobramycin enhanced viscosity ophthalmic solution is well tolerated and has equivalent efficacy to the established treatment regimen with a simplified posology. The formulation provides an alternative therapy for acute bacterial conjunctivitis that should improve patient compliance and satisfaction.

Surgical treatment of vertebral metastasis.

Fifty-seven patients with spinal metastases underwent 60 operations. 36 patients were operated on by anterior approach with decompressive coporectomy and stabilization by metal and methylmetacrylate and 24 patients by laminectomy and/or stabilization by osteosynthesis. Postoperative improvement of the pain syndrome was observed after 56 operations. Neurologic signs were present in 23 patients with paraplegia (5 patients) or paraparesis (18 patients); 15 of the latter patients improved and recovered walking capacity. Two types of metastasis were distinguished: corporal metastasis, in which vertebral wedging and posterior protrusion led to neural deficit, with a good prognosis if treated by anterior surgery, and pericordal metastasis in which the cord compression is due to metastatic proliferation into the spinal canal. Results after decompressive surgery, either by posterior or anterior approaches are more doubtful. Surgery is beneficial and should be preferred to radiation when there is medullary compression by corporal metastasis and also in the presence of intense pain or potential instability of the spine.

[Surgical stabilisation of metastatic fractures of the spine]. / Stabilisation chirurgicale des fractures métastatiques du rachis.

The authors have operated on 15 patients to stabilise metastatic fractures of the spine, either by an anterior approach with replacement of the vertebral body by methyl methacrylate, or by a posterior approach combining laminectomy with spine fixation. The posterior approach was considered to be better in cases of neurological impairment or in lesions of the lower lumbar spine. At cervical, thoracic and thoraco-lumbar levels, the anterior approach was preferred and gave rapid functional improvement. The use of cement allowed early walking without extensive bracing and improved the comfort of the patient. Neurological involvement was a good indication for surgery. In cases without cord lesions, the indications for treatment are related to the comfort of the patient.

[Treatment of secondary cancer of the spine]. / Le traitement du cancer secondaire du rachis.

Sixty spinal metastases have been treated surgically. In 22 cases a posterior approach was made with decompression laminectomy and internal fixation. In 38 others an anterior approach was made to resect the vertebral body and replace it by cement. In the thoracic and lumbar spines, internal fixation after a posterior approach led to secondary displacement in five cases out of nine. In contrast, spines approached anteriorly remain stable. The results were analysed after a follow-up period ranging from six months to four years. In most of the cases there was a dramatic improvement in spinal and radicular pain. Twenty-three cases had neurological impairment and in 15 of them this was improved, sometimes with complete recovery. The authors consider that surgery is indicated in metastasis of the vertebral body with collapse of the vertebra and bony compression of the spinal canal. In these cases radiotherapy is relatively ineffective. In contrast the results obtained after surgery in cases with epidural involvement are not better than those obtained by radiotherapy. Surgery should therefore be used only in radioresistant tumours.

[Immunological screening and follow-up of celiac disease: experience of the University Hospital of Marseille]. / Dépistage et suivi immunologique de la maladie cœliaque : expérience du CHU de Marseille.

PURPOSE: Anti-tissue transglutaminase antibodies (ATTG) have helped to distinguish atypical and silent clinical forms of celiac disease (CD). Immunological diagnosis or follow-up of the disease is now based in France in first line upon IgA ATTG serum evaluation. In the University Hospital of Marseille, the serological diagnosis of CD had consisted during several years in simultaneous determination of both IgA anti-endomysial antibodies (AEA) and IgA ATTG. In literature, few studies focused on the concordance between the two tests and a very few epidemiological data about CD in France are available. METHODS: Five thousand nine hundred and eighty-one patients for whom both AEA and ATTG testing were available were retrospectively included. Characteristics of this cohort were detailed. We numbered and analyzed especially bioclinical charts from patients with AAE/AATG discordance. RESULTS: Among our patients, all ages and all medical subspecialties were represented. Eighty-five new cases of CD were identified. Among the 6516 serum evaluations performed, only 31 tests were discordant. CONCLUSIONS: Our data give information about CD epidemiology in France. They support the contention that ATTG have to be evaluated in first line for CD diagnosis.

[Craniopharyngioma in children: importance of a multidisciplinary approach and therapeutic strategies in the treatment of relapsing]. / Craniofaringioma in età pediatrica: importanza di un approccio multidisciplinare e strategie terapeutiche nel trattamento della forme recidivanti.

The craniopharyngioma is a benign intracranial nonglial tumor derived from a malformation of the embryonic tissue. Represents approximately 6-9% of brain tumors in children. It grows close to the optic nerve, hypothalamus and pituitary. The most frequent histological variety in children is adamantinomatous. The initial symptoms of intracranial hypertension is headache and nausea, followed by visual disturbances, impaired hormonal changes such as the secretion of GH, gonadotropins, TSH and ACTH and central diabetes insipidus. We present the clinical case of MD, 5yrs at age, which shows signs of intracranial hypertension syndrome: neuroradiological findings raise the diagnosis of adamantinomatous craniopharyngioma for which the child underwent to sub-total surgical removal of the lesion and radiosurgery treatment. During the disease develops visual impairment, and secondary diabetes insipidus, hypothyroidism hipocotisolism that takes therapy with desmopressin (Minirin), Cortone acetate and L-tiroxine. For the failure of previous therapies, the child has performed chemotherapy with cisplatin (30 mg/sqm/day) and Etoposide (150 mg/mq/day). A year after the end of the last cycle of chemotherapy was detected new progression of the lesion with the appearance of worsening headache and vomiting in the upright position. TC notes the expansion of the third ventricle and the patient undergoes surgery craniotomy. This clinical case underlines the difficulties in treatment of recurrent craniopharyngioma in situations where the anatomical location do not permit aggressive radical surgery. Anyway, new studies are needed to evaluate the effectiveness of systemic chemotherapy as a method of experimental treatment that could reduce the progression of disease.

Axial MRI index of patellar engagement: a new method to assess patellar instability.

INTRODUCTION: The aim of this study was to define a new index to measure lateral patellar displacement (LPD) using nuclear magnetic resonance imaging (MRI), an axial index of engagement of the patella (AEI) obtained from two different axial MRI views then to validate its use in a prospective series of patients presenting an objective patellar instability (OPI). MATERIALS AND METHODS: One hundred and thirty-five patients with OPI and no history of surgery of the patella were included in a prospective study organized by the French Society of Arthroscopy performed between June 2010 and August 2012. All patients underwent axial and sagittal MRI. The AEI was obtained by projecting predefined patellar and trochlear landmarks (cartilaginous landmarks) on 2 different axial MRI views (one trochlear and one patellar). The results were compared with a series of controls (n=45). RESULTS: The preoperative AEI of the patella was 0.94 ± 0.09 for the control group and 0.84 ± 0.16 for OPI group (P=0.000016). The AEI could be obtained in 100% of the cases if it was measured on 2 MRI views while it could not be measured in 38.5% of the cases if the measurement was only obtained from one MRI view or whenever the widest part of the patella was not across from the femoral trochlea. The AEI did not significantly depend on dysplasia or the presence of a supratrochlear spur. The lowest AIE values were associated with trochlear dysplasia with a supratrochlear spur (P=0.0023) and a more prominent trochlea (P=0.0016). The AEI was correlated with patellar tilt (P<0.000001) and TT-TG on MRI (P<0.000001). DISCUSSION: AEI is a new index to measure LPD. It can be obtained in all cases because it is obtained from two different MRI views. The normal value is close to 1. It can be used to measure patellar instability on the axial plane in patients with OPI, especially in the most severe cases.

The introduction of a new MRI index to evaluate sagittal patellofemoral engagement.

INTRODUCTION: Patella alta is one of the primary factors of patellofemoral instability and its importance lies in the reduced engagement between patella and trochlea during the early degrees of flexion. The evaluation of patellar height is based on conventional x-rays, CT scan and, more recently, MRI. The objective of this multicentric prospective study is to describe a novel index to assess in the sagittal plane the functional engagement between patella and trochlea. MATERIALS AND METHODS: One hundred and thirty-five patients with objective patellar dislocation were prospectively enrolled between April 2010 and September 2011 and were compared with a second group of 45 controls. All patients underwent a standard MRI and a complete radiographic study. Sagittal engagement was measured as the ratio between the articular cartilage of the patella and the trochlear cartilage length measured on two different MRI slices. RESULTS: The mean Sagittal Patellofemoral Engagement (SPE) index was 0.43 ± 0.18 and ranged from 0.02 to 0.913 in the Objective Patellar Dislocation group versus 0.42 ± 0.11 range 0.22 to 0.55 in controls. In the Patellar Dislocation group the mean Caton-Deschamps index was 1.18 ± 0.21 (range 0.71 to 1.91). There were 58 patients with patella alta, in whom the mean SPE was 0.39 ± 0.18 (range 0.02 to 0.87). Sagittal engagement was significantly higher when compared with patients in the Patellar Dislocation group who had no patella alta (mean 0.46 ± 0.16, range 0.1-0.913). DISCUSSION: The present study introduces a new method to measure the SPE with the use of MRI. The evaluation of the functional engagement of the patella with the femoral trochlea in the sagittal plane can serve as a supplementary tool to the existing methods of evaluating patellar height, and may help to better identify the cases where inadequate engagement is recorded despite the absence of patella alta, so that the need for tibial tuberosity osteotomy may be re-assessed.