Predictive factors of revision stapes surgery in otosclerosis.

OBJECTIVES: This study aimed to investigate predictive factors for revision surgery in otosclerosis. METHODS: This was a retrospective, multicentre study in four tertiary centres. The primary objective was to investigate factors that were predictive of the need for revision stapes surgery. RESULTS: The 'revision' group included 145 patients, and the 'control' group included 143 patients. This study identified statistically significant predictive factors for the need for revision surgery: younger age, active smoking status, dyslipidaemia and high blood pressure. There was no statistically significant difference between the two groups in terms of surgical technique or stapedotomy technique. CONCLUSION: This study showed that patients who are candidates for primary stapes surgery with younger age, active smoking status, dyslipidaemia and high blood pressure are at higher risk of needing revision surgery. A holistic approach prior to stapes surgery with multidisciplinary assessment is recommended. These results are important for better patient counselling on expected outcomes and risks.

Compact X-Band Electron Linac for Radiotherapy and Security Applications.

RadiaBeam has developed a 6 MeV accelerator that is compact and light enough to be placed on a robotic arm or light truck. The main drivers of size and weight in conventional accelerators are the power source and the shielding. Small dimensions are enabled by operation at 9.3 GHz frequency (X-band), which allows reducing the size and weight of all accelerator components. Thanks to the robust design of the accelerating structure, the accelerator can be used as a source for novel cargo inspection and radiotherapy techniques. In this paper, we present the linac design and its components, as well the results of the experimental demonstration of beam acceleration.

Delayed care for patients with newly diagnosed cancer due to COVID-19 and estimated impact on cancer mortality in France.

BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.

Critical steps in the isolation and expansion of adipose-derived stem cells for translational therapy.

Since the discovery of adipose-derived stem cells (ASCs), there have been high expectations of their putative clinical use. Recent advances support these expectations, and it is expected that the transition from pre-clinical and clinical studies to implementation as a standard treatment modality is imminent. However ASCs must be isolated and expanded according to good manufacturing practice guidelines and a basic assurance of quality, safety, and medical effectiveness is needed for authorisation by regulatory agencies, such as European Medicines Agency and US Food and Drug Administration. In this review, a collection of studies investigating the influence of different steps of the isolation and expansion protocol on the yield and functionality of ASCs has been presented in an attempt to come up with best recommendations that ensure potential beneficial clinical outcome of using ASCs in any therapeutic setting. If the findings confirm the initial observations of beneficial effects of ASCs, the path is paved for implementing these ASC-based therapies as standard treatment options.

Importance of malnutrition and associated diseases in the management of Zenker's diverticulum.

OBJECTIVES: To study the impact of malnutrition on a population treated for Zenker's diverticulum and to look for the causes of persistence or recurrence of dysphagia after endoscopic surgery. MATERIAL AND METHODS: This retrospective study included 30 patients with Zenker's diverticulum treated by endoscopy. All swallowing disorders and manifestations of malnutrition and postoperative improvement in and/or recurrence of symptoms were noted. RESULTS: Nutritional status was evaluated for 26 patients. Before surgery, 54% suffered from malnutrition, which was severe in 31%; 28.6% of the cases with malnutrition showed postoperative complications, versus 8.3% of cases without baseline malnutrition. Ninety percent of patients (n=27) declared complete resolution of symptoms. Nine patients presented recurrence of dysphagia, including 6 with recurrence of Zenker's diverticulum and 3 with, respectively, inclusion body myopathy, esophageal hypertonia and central disease. CONCLUSION: Malnutrition should be quantified and treated before and after surgery for Zenker's diverticulum to prevent complications and decrease mortality. Associated pathologies should be systematically screened for, especially in case of recurrence of swallowing disorder without recurrence of Zenker's diverticulum.

[Brachytherapy in France: current situation and economic outlook due to the unavailability of iridium wires]. / Curiethérapie en France : état des lieux et perspectives économiques après l'arrêt de la commercialisation des fils d'iridium.

In 2013, about 6000 patients were treated with brachytherapy, the number diminishing by 2.6% per year since 2008. Prostate, breast and gynecological cancers are the most common types of cancers. Since 2008, the number of brachytherapy facilities has decreased by 18%. In medicoeconomic terms, brachytherapy faces many problems: the coding system is outdated; brachytherapy treatments cost as much as internal radiation; fees do not cover costs; since iridium wire has disappeared from the market, the technique will be transferred to more expensive high-speed or pulse dose rates. The French financing grid based on the national study of costs lags behind changes in such treatments and in the best of cases, hospitals resorting to alternatives such as in-hospital brachytherapy are funded at 46% of their additional costs. Brachytherapy is a reference technique. With intense pressure on hospital pricing, financing brachytherapy facilities will become even more problematic as a consequence of the disappearance of iridium 192 wires. The case of brachytherapy illustrates the limits of the French financing system and raises serious doubts as to its responsiveness.

[Assessing the feasibility and the acceptability of outpatient retinal detachment surgery]. / Évaluation de la faisabilité et de l'acceptabilité de la prise en charge en ambulatoire des patients opérés de décollement de rétine.

PURPOSE: To assess the feasibility and acceptability of outpatient care for patients undergoing surgery for retinal detachment. PATIENTS AND METHODS: Patients successively undergoing retinal detachment surgery between January and November 2012 were prospectively included. Patient age, distance from home, type of detachment, surgical technique, postoperative intravenous medications if applicable, pain as evaluated on the visual analogue scale (VAS), slit lamp findings on the day of surgery (D0) and the next day (D1), the presence of another person in the home, comprehension of instructions, the patient's physical abilities and adherence to outpatient treatment were recorded. RESULTS: Forty-six surgeries on 17 women and 28 men, including 2 one-eyed patients, with a mean age of 62 years (±16.6; 19-95), were studied. The mean distance from home was 78km (±108; 1-490 km). The surgery was performed ab-interno in 44 cases (40 transconjunctival, 4 cases of disinsertion with placement of a buckle) and ab-externo in 2 cases; under general anesthesia in 40 cases and local/regional anesthesia in 6 cases. Five cases were recurrent detachments, lensectomy was performed in 6 cases, internal gas tamponade was performed in the majority of cases (4 with silicone oil and 1 without tamponade). Functional signs were absent or limited to simple discomfort in 95.7% of cases on D0 as well as D1. The mean VAS at D0 was very low, described as 0.32/10 (0-8) and 0.63/10 (0-5) at D1. Two patients vomited on D0 and one on D1. Mean intraocular pressure was 12.8mmHg (±4.4; 4-24) at D0 and 17.6mmHg (±6.3; 8-34) at D1. The retina was visible in 91.3% of cases on D0 and 89.1% of cases on D1. Sleepiness was present in 3 cases (6.5%) at the D0 exam, and returning home was impossible without assistance from a third party in 4 cases (8.7%) (this incapacity was permanent or related to the patient's one-eyed status in all cases). The instructions for proper positioning were assimilated by all patients on D0, and no intravenous treatment was necessary after awakening. A companion was present at home in 78.3% (n=36) of cases; 87% (n=40) of the patients felt they could return home on D0 had it been necessary, with an early return home even desired by 32.6% (n=15) of the patients. DISCUSSION: The changes in surgical management of retinal detachment patients and the appearance in France of a specific fee schedule now make it possible to consider ambulatory treatment of patients with retinal detachment. CONCLUSION: Outpatient management of retinal detachment patients appears perfectly feasible and acceptable according to this study.

[NT-proBNP measurement on Immulite 2500 (DPC): analytical performance and comparison with Roche Diagnostics and Dade-Behring NT-proBNP immunoassays]. / Dosage du NT-proBNP sur l'Immulite 2500 (DPC): évaluation analytique et comparaison avec les trousses Roche-Diagnostics et Dade-Behring.

The measurement of the N-terminal part of the proBNP (NT-proBNP) may be used to assess the secretion of the B-type natriuretic peptide (BNP), a marker of heart failure. In this study, we have evaluated the NT-proBNP immunoassay proposed by DPC Company for the Immulite 2500 analyzer and compared the results with those obtained with the two other immunoassays respectively commercialized by Roche Diagnostics (Elecsys 2010 analyzer) and Dade-Behring (Dimension RXL). The obtained results show very good general performance of the DPC's technique with a CV inferior to 8% for the values superior to 40 ng/L. The within run CVs are 3.1, 3.5 and 3.5% and the between run CVs are 3.8, 4.7 and 4.8% for the NT-proBNP levels of 151, 1601 and 5255 ng/L, respectively. We found a very good correlation between DPC's and Roche Diagnostics's assays (regression analysis: y = 0.88 x + 25.2 ; r = 0.998) and DPC's and Dade-Behring assays (regression analysis: y = 0.93 x + 16.4 ; r = 0.997). Although a small bias appeared between these assays, similar cut-points may be used to exclude both heart failure in ambulatory patients and cardiac origin in acute dyspnea.

Insulin-related growth factors stimulate proliferation of retinal progenitors in the goldfish.

The retina of the adult goldfish grows throughout the life of the animal, in part, by the continual addition of new neurons. Further, destruction of extant neurons in this tissue stimulates neuronal regeneration. In an attempt to identify growth factors that regulate both normal and injury-stimulated neurogenesis, we used organ culture techniques and tested nine peptide growth factors for their ability to modulate cell proliferation in both normal retinas and retinas with lesions. Of the growth factors tested, only the insulin-related peptides (insulin and insulin-like growth factors I and II) consistently stimulated proliferation, and this was restricted to the retinal progenitors within the circumferential germinal zone. None of the growth factors tested stimulated proliferation of rod precursors (cells in the mature retina whose progeny are exclusively rod photoreceptors) or the injury-stimulated retinal progenitors. Although the negative data are subject to multiple interpretations, these data suggest that in the retina of the adult goldfish, insulin-related peptides regulate proliferation of retinal progenitors within the circumferential germinal zone, but molecules that modulate the proliferation of the rod precursors or injury-induced retinal progenitors in the retina of the adult goldfish have yet to be identified.

Isoenzyme diversity in Pneumocystis carinii from rats, mice, and rabbits.

Pneumocystis carinii is an opportunistic pathogen that causes pneumonia in immunocompromised patients. To investigate the genetic diversity of P. carinii populations, multilocus enzyme electrophoresis was used to analyze five enzyme systems (malate dehydrogenase, glucose phosphate isomerase, leucine aminopeptidase, malic enzyme, and 6-phosphogluconate dehydrogenase). Only five different multilocus associations (zymodemes) were recorded for the 70 isolates studied. While only one multilocus combination was found in mice and rabbits, three different multilocus associations were recorded in rats. Population genetic tests and phylogenetic analysis strongly suggest that P. carinii genotypes are host-specific, in agreement with molecular study results, and that no genetic exchange occurs between genotypes from different host species. This hypothesis could be verified only by the evolutionary genetic approach, which relies here on multilocus analysis.

Is paclitaxel and cisplatin a cost-effective first-line therapy for advance ovarian carcinoma?

BACKGROUND: Paclitaxel and cisplatin use for the treatment of advanced ovarian carcinoma (AOC) has been shown to increase median survival duration. An evaluation was performed on the economic consequences of treating AOC patients with combined paclitaxel and cisplatin chemotherapy compared with current usual care, i.e., combined cyclophosphamide and cisplatin chemotherapy. METHODS: Linear modeling techniques combined with retrospective chart analysis were used to predict the clinical progression and treatment of AOC patients until death. Cost-effectiveness analysis comparing paclitaxel and cisplatin and usual care was performed from a simplified Ministry of Health perspective. RESULTS: Assuming a 50% increase in survival for paclitaxel and cisplatin patients, an assumption supported by recent clinical trial data, this treatment showed an average lifetime cost per patient of $50,054 Cdn compared with a cost of $36,837 Cdn for usual care. The incremental cost of the paclitaxel and cisplatin treatment over the usual treatment was $20,355 Cdn per life year gained. These results withstood extensive sensitivity analyses. CONCLUSIONS: Paclitaxel, in combination with cisplatin, appears to be a cost-effective first-line treatment for AOC. A moderate increase in incremental cost compares favorably with other life-saving strategies currently in use. As more data become available for the use of paclitaxel, this pilot study will provide a basis for more extensive economic evaluation of paclitaxel.

Excystation of in vitro-derived Giardia lamblia cysts.

This is the first in-depth analysis of the excystation of Giardia lamblia cysts prepared in vitro. Its goals were both to achieve efficient excystation and to gain insights into this crucial but poorly understood process. To identify the critical elements of excystation, we tested the sequential low-pH induction and protease treatments which had been reported to be important for excystation of fecal cysts. The optimal pH for induction of excystation was 4.0. Emergence was greatly (approximately 10-fold) stimulated by subsequent exposure of in vitro-derived cysts to chymotrypsin, trypsin, or human pancreatic fluid. The stimulatory activity of each was abolished by soybean trypsin inhibitor, demonstrating that the activity of pancreatic fluid was due to these proteases. Excystation of in vitro-derived cysts was approximately 10 to 38%. Although the walls of in vitro-derived cysts were partially digested by protease treatment, trophozoites emerged only from one pole, as observed with fecal cysts. The conditions of encystation also determined the efficiency of excystation. Specifically, encystation in the presence of lactic acid, a major metabolite of colonic bacteria, stimulated excystation approximately fourfold, although it did not increase the total numbers of cysts. These experiments have shown that excystation of in vitro-derived cysts reflects that of cysts purified from human feces in that it is dependent upon conditions which simulate the passage of cysts through the human stomach (low pH) and into the small intestine (pancreatic proteases).

Giardia lamblia: the roles of bile, lactic acid, and pH in the completion of the life cycle in vitro.

Large numbers (10(4) to greater than 10(5)/ml) of Type I water-resistant Giardia lamblia cysts were produced in vitro under conditions that are characteristic of the human intestinal lumen. We define Type I cyst morphology as oval shaped, smooth, and refractile, with cyst wall, axostyle, and median body visible in relief by Normarski differential interference contrast optics. Human and porcine bile induced higher levels of encystation than bovine bile at the alkaline pH (7.8) which occurs in the human lower small intestine. High-pressure liquid chromatography analysis showed that the porcine bile had a preponderance of hyocholate, rather than cholate, while bovine bile had less chenodeoxycholate and more deoxycholate than human bile. Lactic acid, a major product of bacterial metabolism in the human colon, further stimulated encystation. Growth of the preencystation culture without bile also increased subsequent encystation. More than 90% of Type I cysts produced with porcine bile plus lactic acid were viable as indicated by the uptake and retention of fluorescein diacetate and exclusion of propidium iodide. Biological activity of in vitro-derived water-resistant cysts was demonstrated by the observation that 1 to 9.5% excysted in vitro. The percentage of excystation was greatly decreased following encystation at pH 7.0 or by omission of bile or lactic acid. This is the first quantitative in vitro demonstration of the complete life cycle of G. lamblia from humans.

Small-intestinal factors promote encystation of Giardia lamblia in vitro.

Bile salts and fatty acids stimulated differentiation of cultured Giardia lamblia trophozoites into water-resistant cysts at the slightly alkaline pH of the small intestinal lumen. Maximum encystation occurred at pH 7.8. Thus, specific small-intestinal factors may influence encystation in vivo as well as in vitro.