Intralesional ethanol in the treatment of unresectable liver cancer

Percutaneous ethanol injection (PEI) under ultrasonography guidance has been widely tried in not advanced hepatocellular carcinoma (HCC). Ten years after the introduction of PEI, some conclusions of its indications can be drawn. In our series, 210 cirrhotic patients were treated; 141 with multisession PEI in an outpatient clinic, 57 with single session PEI under general anesthesia, and 12 with both. The 1-, 3-, and 5-year survival rates (by Kaplan-Meier method) were 93%, 65%, and 41% for Child class A patients with single HCC 5 cm, and 88%, 47%, and 33% for patients with multiple HCC up to five lesions 5 cm. In these patients the local recurrence rate was 15% and the new lesion rate at the 5-year follow-up was 74%. One death due to hemorrhage from esophageal varices in a Child class C patient treated by single session PEI occurred. The large number of cirrhotic patients enrolled in ultrasonography screening programs has created a large demand for effective, safe, repeatable, low-cost treatment that can be offered at many centers. PEI meets all these requirements. PEI is proposed as the treatment of choice for the mentioned patients, excluding candidates for liver transplantation and surgical resection according to the predictive adverse factors currently in use. Single session technique widened the indications of traditional PEI to larger lesions.

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Resumen La inyección percutánea de etanol (IPE) bajo guía ultrasonográfica ha sido ampliamente ensayada en carcinoma hepatocelular (CHC) no avanzado. Transcurridos diez años luego luego de la introducción de la IPE, se pueden sacar conclusiones pertinentes a su indicación: En nuestra serie, se trataron 200 pacientes cirróticos, 141 de ellos con IPE en múltiples sesiones en forma ambulatoria, 57 con una sesión única de IPE bajo anestesia generaly y 12 con ambas modalidades. Las tasas de sobrevida a 1, 3 y 5 años (por el método de Kaplan-Meier) fueron 93%, 65%, 41% en los pacientes en clase Child-A con CHC único de 5 cm, y 88%, 47% 33% en CHC múltiple de hasta 5 lesiones de 5 cm. En estos pacientes la tasa de recurrencia local fue 15% y la tasa de nuevas lesiones a los 5 años de seguimiento fue de 54%. Se presentó una muerte por hemorragia de várices esofágicas en un paciente en clase Child-C tratado con una sesión única de IPE. El gran número de pacientes cirróticos incorporados a programas de tamizaje con ultrasonido ha creado una gran demanda por tratamientos eficaces, seguros, reproducibles y de bajo costo. El IPE llena todos estos requerimientos. Se propone el IPE como el tratamiento de escogencia para los pacientes arriba mencionados, haciendo exclusión de los candidatos para transplante hepático y para resección quirúrgica de acuerdo con los factores adversos de pronóstico actualmente en uso. La técnica de une sesión única ha ampliado las significaciones tradicionales del IPE para ser aplicada a lesiones de mayor tamaño.

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Résumé L'alcoolisation par injection percutanée (APC) sous échographie est utilisée pour traiter des carcinomes hépatocellulaires (CHC) peu volumineux. Dix ans après l'introduction de la technique d'APC, on peut tirer des conclusions quant à es indications. Dans notre expérience, 210 patients cirrhotiques ont été traités: 141 ont été traités par APC en ambulatoire, 57 en «séance unique» sous anesthésie et 12 par les deux. La survie à 1, 3 et 5 ans (méthode de Kaplan-Meier) était respectivement de 93, de 65 et de 41 % pour les patients ayant une lésion unique 5 cm, classés Child A, et de 88, de 47 et de 33% chez les patients ayant des lésions multiples mais inférieures au nombre de 5, toujours 5 cm. Chez ces patients, le taux de récidive locale était de 15% et le taux de nouvelles lésions à 5 ans, de 74%. Il y a eu un décès par hémorragie en rapport avec une rupture de varices oesophagiennes chez un patient Child C traité en une seule séance d'APC. Le nombre croissant de patients actuellement soumis, à une surveillance par échographie va de paire avec un traitement efficace, sûr, de coût réduit, et facilement disponible dans de nombreux centres. L'APC répond à toutes ces conditions. L'APC peut être proposée comme traitement de choix pour des patients répondant aux critères suscités, en excluant les candidats à la transplantation ou ceux qui peuvent être traités chirurgicalement. Les indications de la technique préconisée ici, en une seule séance, s'élargissent actuellement à des lésions plus volumineuses.

     

Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts

Purpose

Uncertainties remain regarding the clinical efficacy of ovarian tissue cryopreservation and grafting. We report a retrospective analysis of reproductive outcomes and lessons learnt following 55 ovarian tissue transplant procedures at our center from 2006 to 2019.

Methods

We analyzed variables related to graft success such as tissue volume, follicular density, total follicular volume, and age on the duration of graft function.

Results

Follicular density and total follicular volume correlate positively with duration of graft function. All clinical pregnancies in our cohort occurred in women who were aged 35 or less at the time of ovarian tissue cryopreservation.

Conclusion

Graft success, as determined by eventual pregnancy and the longevity of graft function, may be impacted by factors including age at cryopreservation, follicular density, and total follicular volume.

     

Phase I trial and pharmacokinetics of fenretinide in children with neuroblastoma.

PURPOSE: Fenretinide (4HPR), a synthetic retinoid, induces apoptosis in neuroblastoma cells. A Phase I study in children with neuroblastoma was designed to determine maximum tolerated dose, toxicity, and pharmacokinetics. EXPERIMENTAL DESIGN: Fifty-four patients received oral 4HPR, once daily, for 28 days, followed by a 7-day interruption, for up to 6 courses. The starting dose was 100 mg/m(2)/day. At least 3 patients were entered at each escalating 4HPR dose level. Pharmacokinetic sampling was performed on days 1 and 28 of the first course. RESULTS: Fifty-four patients, of whom 53 were evaluable, received doses between 100 and 4000 mg/m(2)/day for a total of 168 courses. Additional dose escalation was precluded by capsule number intake. A total of 34 of 53 evaluable patients showed manageable, reversible toxicities, which were not dose related. One dose-limiting toxicity (nyctalopia grade 3) occurred after the 1000 mg/m(2)/day dose. Twelve patients showed grade 2 toxicity: skin xerosis (6 cases); nyctalopia (3 cases); hepatic toxicity (1 case); diarrhea (1 case); and headache (1 case). Stable disease was observed in 41 patients for a median period of 23 months (range 2-35+). After first administration, average 4HPR peak plasma levels ranged from 0.6 to 6 micro M (after 100 and 4000 mg/m(2)/day, respectively) and increased 2-fold (to 1.3 and 12.9 micro M, respectively) after the 28-day treatment. 4HPR half-life increased from 17 h after the first administration to 25 h after the 28(th) administration. Incidence of grade 2-3 toxicity was 0 of 12 (0%), 7 of 22 (31%), and 4 of 8 (50%) with peak 4HPR concentrations <3 micro M, 3-10 micro M, and >10 micro M, respectively. After repeated treatment, retinol levels decreased from 20 to 10% of pretreatment levels after all of the doses. CONCLUSIONS: In children, 4HPR administration up to 4000 mg/m(2)/day over 28 days, followed by a 7-day interruption, results in manageable toxicity and in drug plasma concentrations comparable with those that induce apoptosis in neuroblastoma cell lines.     

Assessment of chitosan derivatives as buccal and vaginal penetration enhancers.

The aim of the present work was to evaluate the mucoadhesive and penetration enhancement properties via the buccal and vaginal mucosae of four different chitosan derivatives: 5-methyl-pyrrolidinone chitosan (MPC), two low molecular weight chitosans (DC1 and DC2) and a partially reacetylated chitosan (RC). Chitosan HCl was used as a reference. Polymer solutions (4% w/w) were prepared in media simulating the buccal (pH 6.4 buffer or water) and the vaginal (pH 5.0 buffer) environments and subjected to rheological characterization. Acyclovir was added to the polymer solutions at 5% (w/w) concentration. The mucoadhesive properties of the polymer solutions were measured using excised porcine cheek or vaginal mucosa and mucin dispersions to simulate the buccal or vaginal environments, respectively. Drug permeation and penetration tests were carried out using porcine cheek and vaginal mucosae as model membranes. Acyclovir aqueous suspensions prepared in pH 6.4 and 5.0 buffers were used as blanks. Drug release measurements were also carried out in the same conditions employed for the permeation and penetration tests. Methyl-pyrrolidinone chitosan shows the best mucoadhesive and penetration enhancement properties in both buccal and vaginal environments. The capability to enhance the permeation/penetration of acyclovir was decreased by partial depolymerization of chitosan and disappeared after partial reacetylation.     

Obesity and Dysmetabolic Factors among Deceased COVID-19 Adults under 65 Years of Age in Italy: A Retrospective Case-Control Study

Background: Italy has witnessed high levels of COVID-19 deaths, mainly at the elderly age. We assessed the comorbidity and the biochemical profiles of consecutive patients ≤65 years of age to identify a potential risk profile for death. Methods: We retrospectively analyzed clinical data from consecutive hospitalized-for-COVID-19 patients ≤65 years, who were died (593 patients) or discharged (912 patients) during February–December 2020. Multivariate logistic regression identified the mortality risk factors. Results: Overweight (adjusted odds ratio (adjOR) 5.53, 95% CI 2.07–14.76), obesity (adjOR 8.58, CI 3.30–22.29), dyslipidemia (adjOR 10.02, 95% CI 1.06–94.22), heart disease (adjOR 17.68, 95% CI 3.80–82.18), cancer (adjOR 13.28, 95% CI 4.25–41.51) and male sex (adjOR 5.24, 95% CI 2.30–11.94) were associated with death risk in the youngest population. In the older population (46-65 years of age), the overweight and obesity were also associated with the death risk, however at a lower extent: the adjORs varyied from 1.49 to 2.36 for overweight patients and from 3.00 to 4.07 for obese patients. Diabetes was independently associated with death only in these older patients. Conclusion: Overweight, obesity and dyslipidemia had a pivotal role in increasing young individuals’ death risk. Their presence should be carefully evaluated for prevention and/or prompt management of SARS-CoV2 infection in such high-risk patients to avoid the worst outcomes.     

“One Degree of Separation”: A Mixed-Methods Evaluation of Canadian Mental Health Care User and Provider Experiences With Remote Care During COVID-19

ObjectivesThe COVID-19 pandemic has contributed to a shift from in-person to remote mental health care. While remote care methods have long existed, their widespread use is unprecedented. There is little research about mental health care user and provider experiences with this transition, and no published studies to date have compared satisfaction between these groups.MethodsCanadian mental health care users (n = 332) and providers (n = 107) completed an online self-report survey from October 2020 to February 2021 hosted by the Canadian Biomarker Integration Network in Depression. Using a mixed-methods approach, participants were asked about their use of remote care, including satisfaction, barriers to use, helpful and unhelpful factors, and suggestions for improvement.ResultsOverall, 59% to 63% of health care users and 59% of health care providers were satisfied with remote care. Users reported the greatest satisfaction with the convenience of remote care, while providers were most satisfied with the speed of provision of care; all groups were least satisfied with therapeutic rapport. Health care providers were less satisfied with the user-friendliness of remote care (P < 0.001) than users, while health care users were less satisfied than providers with continuity of care (P < 0.001). The use of a video-based platform was associated with remote care satisfaction among health care users (P < 0.02), and qualitative responses support the importance of visual cues in maintaining therapeutic rapport remotely. The majority of users (55%) and providers (87%) reported a likelihood of using remote care after the pandemic.ConclusionsRemote mental health care is generally accepted by both users and providers, and the majority would consider using remote care following the pandemic. Suggestions for improvement include greater use of video, increased attention to body language and eye contact, consistency with in-person care, as well as increased provider training and administrative support.     

Risk to human health associated with the environmental occurrence of cyanobacterial neurotoxic alkaloids anatoxins and saxitoxins

Cyanobacteria are ubiquitous photosynthetic micro-organisms forming blooms and scums in surface water; among them some species can produce cyanotoxins giving rise to some concern for human health and animal life. To date, more than 65 cyanobacterial neurotoxins have been described, of which the most studied are the groups of anatoxins and saxitoxins (STXs), comprising many different variants. In freshwaters, the hepatotoxic microcystins represent the most frequently detected cyanotoxin: on this basis, it could appear that neurotoxins are less relevant, but the low frequency of detection may partially reflect an a priori choice of target analytes, the low method sensitivity and the lack of certified standards. Cyanobacterial neurotoxins target cholinergic synapses or voltage-gated ion channels, blocking skeletal and respiratory muscles, thus leading to death by respiratory failure. This review reports and analyzes the available literature data on environmental occurrence of cyanobacterial neurotoxic alkaloids, namely anatoxins and STXs, their biosynthesis, toxicology and epidemiology, derivation of guidance values and action limits. These data are used as the basis to assess the risk posed to human health, identify critical exposure scenarios and highlight the major data gaps and research needs.