Pharmacokinetics of bleomycin sclerotherapy in patients with vascular malformations

alexandrossfakianakis shared this article with you from Inoreader Pharmacokinetics of bleomycin sclerotherapy in patients with vascular malformations Via Pediatric Blood & Cancer Abstract Bleomycin, a chemotherapy agent that inhibits synthesis of DNA, has been increasingly utilized in sclerotherapy for patients with vascular malformations. A serious long-term risk of intravenous bleomycin is dose-dependent interstitial pneumonitis. Little is known about absorption and circulating levels of bleomycin when used in sclerotherapy for patients with vascular malformations. This is an Institutional Review Board (IRB)-approved prospective study on patients receiving bleomycin sclerotherapy in the management of vascular malformations. Depending on the type of vascular malformation, bleomycin was administered either in the lumen or interstitial space of the involved lesion. A bleomycin assay measured serum bleomycin plasma concentrations versus time at seven intervals following treatment. Pharmacokinetic parameters were obtained for each participant and included peak plasma concentration (C max), time to reach peak plasma concentration (T max), volume of distribution (V d), elimination half-life (t 1/2), the volume of plasma cleared of the drug per unit time (CL), and total systemic exposure area under the curve (AUC). Fifteen patients were enrolled (5: lymphatic, 4: venous, 6: arteriovenous malformations). Bleomycin was administered interstitially (IS) in 11 patients and intraluminal (IL) in four; median age of 13 years (range: 2–67). Pharmacokinetic analysis revealed terminal elimination half-life (t 1/2λz) of 88.51 (±23.09) and 111.61 (±37.75) minutes for the IS and IL groups, respectively. V d was 4.86 L (±6.74) and 1.55 L (±0.54) for the IS and IL groups, respectively. AUC was 53.9 (±23.45) and 129.17 (±93.57) mg min/L for the IS and IL groups, respectively. There were no statistically significant differences in t 1/2λz, V d, or AUC parameters between groups. Bleomycin is absorbed systemically when used as a sclerosant for vascular malformations when injected either IS or IL. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Local control of parameningeal rhabdomyosarcoma: An expert consensus guideline from the International Soft Tissue Sarcoma Consortium (INSTRuCT)

alexandrossfakianakis shared this article with you from Inoreader Local control of parameningeal rhabdomyosarcoma: An expert consensus guideline from the International Soft Tissue Sarcoma Consortium (INSTRuCT) Via Pediatric Blood & Cancer Abstract The International Soft Tissue Sarcoma Database Consortium (INSTRuCT) consists of a collaboration between the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee, the European pediatric Soft Tissue Sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). As part of the larger initiative of INSTRuCT to provide consensus expert opinions for clinical treatment of pediatric soft tissue sarcoma, we sought to provide updated, evidenced-based consensus guidelines for local treatment of parameningeal rhabdomyosarcoma using both existing literature as well as recommendations from the relevant cooperative group clinical trials. Overall, parameningeal rhabdomyosarcoma represents a distinctly challenging disease to treat, given its location near many critical structures in the head and neck, frequently advanced local presentation, and predilection for local failure. Definitive chemoradiation remains the standard treatment approach for parameningeal rhabdo myosarcoma, with surgery often limited to biopsy or salvage therapy for recurrent disease. In this consensus paper, we specifically discuss consensus guidelines and evidence for definitive local management with radiotherapy, with a focus on imaging for radiotherapy planning, dose and timing of radiation, approach for nodal irradiation, various radiation techniques, including proton therapy, and the limited role of surgical resection. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

68Ga‐DOTATATE PET and functional imaging in pediatric pheochromocytoma and paraganglioma

alexandrossfakianakis shared this article with you from Inoreader 68Ga‐DOTATATE PET and functional imaging in pediatric pheochromocytoma and paraganglioma Via Pediatric Blood & Cancer Abstract Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors in childhood. Up to 40% of PPGL are currently thought to be associated with a hereditary predisposition. Nuclear medicine imaging modalities such as fluorodeoxyglucose positron emission tomography (18F-FDG PET), 68Ga-DOTATATE PET, and 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy play an essential role in the staging, response assessment, and determination of suitability for targeted radiotherapy in patients with PPGL. Each of these functional imaging modalities targets a different cellular characteristic and as such can be complementary to anatomic imaging and to each other. With the recent US Food and Drug Administration approval and increasing use of 68Ga-DOTATATE for imaging in children, the purpose of this article is to use a case-based approach to highlight both the advantages and limitations of DOTATATE imaging as it is compared to current radiologic imaging techniques in the staging and response assessment of pediatric PPGL, as well as other neuroendocrine malignancies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel smartphone‐based intervention targeting sleep difficulties in individuals experiencing psychosis: A feasibility and acceptability evaluation

alexandrossfakianakis shared this article with you from Inoreader A novel smartphone‐based intervention targeting sleep difficulties in individuals experiencing psychosis: A feasibility and acceptability evaluation Via Psychology and Psychotherapy: Theory, Research and Practice Abstract Objectives Cognitive Behavioural Therapy (CBT) is an effective psychological intervention for sleep difficulties and has been used successfully in individuals with psychosis. However, access is restricted due to lack of resources and staff training. Delivering CBT for sleep problems using smartphone technology may facilitate wider access. This study aimed to evaluate the feasibility, acceptability and potential usefulness of a guided, smartphone-based CBT intervention targeting sleep disturbance for individuals with psychosis. Design Participants with psychosis spectrum diagnoses were recruited to a single-arm, uncontrolled study and engaged with the seven-module programme via smartphone app for six weeks with therapist support. Method Feasibility was assessed by rates of referral, recruitment and completion. Acceptability was assessed by app usage, a satisfaction questionnaire and qualitative analysis of participants' semi-structured interview. Pre- and post-intervention assessment of sleep, psychotic experiences, mood, well-being and functioning was conducted. Mean change confidence intervals were calculated and reported as an indication of usefulness. Results Fourteen individuals consented to participation, and eleven completed the post-intervention assessment. On average, each participant engaged with 5.6 of 7 available modules. Qualitative feedback indicated the intervention was considered helpful and would be recommended to others. Suggested improvements to app design were provided by participants. Potential treatment benefits were observed for sleep difficulties, and all outcomes considered, except frequency of hallucinatory experiences. Conclusions It is feasible and acceptable to deliver therapist-guided CBT for sleep problems by smartphone app for individuals with psychosis. This method provides a low-intensity, accessible intervention, which could be offered more routinely. Further research to determine treatment efficacy is warranted. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of a mouth rinse and a high-fluoride toothpaste on caries incidence in orthodontic patients: A randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader Effect of a mouth rinse and a high-fluoride toothpaste on caries incidence in orthodontic patients: A randomized controlled trial Via American Journal of Orthodontics and Dentofacial Orthopedics Publication date: Available online 28 April 2022 Source: American Journal of Orthodontics and Dentofacial Orthopedics Author(s): Hanna Enerbäck, Peter Lingström, Marie Möller, Cathrine Nylén, Cecilia Ödman Bresin, Ingrid Östman Ros, Anna Westerlund View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Differences in craniofacial morphology between platybasic and nonplatybasic patients with velopharyngeal dysfunction and control subjects

alexandrossfakianakis shared this article with you from Inoreader Differences in craniofacial morphology between platybasic and nonplatybasic patients with velopharyngeal dysfunction and control subjects Via American Journal of Orthodontics and Dentofacial Orthopedics Publication date: Available online 28 April 2022 Source: American Journal of Orthodontics and Dentofacial Orthopedics Author(s): Ariela Nachmani, Muhamed Masalha, Ameen Biadsee, Ben Nageris, Tom Ben-Dov, Firas Kassem View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Medicine, Religion, and the Humanitarian Ethos:

alexandrossfakianakis shared this article with you from Inoreader Medicine, Religion, and the Humanitarian Ethos: Walter B. Cannon, Unitarianism, and the Care of Spanish Republican Refugees in France Via Journal of the History of Medicine and Allied Sciences - current issue Abstract Biographies of Walter B. Cannon (1871-1945) usually present two sides of his life: one, where he was an outstanding man of science in the United States during the so-called "Golden Age of Medicine," and the other, where he was a leading humanitarian activist engaged in myriad causes, notably in the defense of Spanish democracy during the Civil War (1936-1939). However, these biographies fail to take into account that the apparent link between these two sides of his life was his religious conviction.This study summarizes the aims and accomplishments of the American Medical Bureau to Aid the Spanish Democracy (AMBASD) of which Cannon was chair between 1937 and 1939. Then, it examines Cannon's inspirational role on the international relief work with Spanish Republican refugees in France, through the case of the Varsovie Hospital of Toulouse that between 1945 and 1949 was jointly managed by the Unitarian Service Committee (USC) and the Joint An ti-Fascist Refugee Committee (JAFRC), and renamed Varsovie Hospital/Walter B. Cannon Memorial in recognition of the Spanish Republicans' debt for his extraordinary contribution during the Spanish Civil War and beyond. Finally, the article investigates the Unitarian roots of Cannon's humanitarian ethos by exploring the historical relations of this religious movement with science and with many major actors at Harvard University as well as the links of Cannon's relatives to Unitarianism.The analysis reveals Unitarianism's influence on Cannon's views about science, democracy, and liberty, as well as on his remarkable involvement in the medical solidarity movement with the Second Spanish Republic and other similar commitments. In sum, it shows how important is to branch out in our studies of medical and scientific practice to include practitioners' broader social and religious communities in order to understand their motivations, achievements, and behavior. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Simulation CT-based radiomics for prediction of response after neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer

alexandrossfakianakis shared this article with you from Inoreader Simulation CT-based radiomics for prediction of response after neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer Via Radiation Oncology - Latest Articles To report on the discriminative ability of a simulation Computed Tomography (CT)-based radiomics signature for predicting response to treatment in patients undergoing neoadjuvant chemo-radiation for locally ad... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Primary cheilorhinoseptoplasty using the Talmant protocol in unilateral complete cleft lip: functional and aesthetic results on nasal correction and comparison with the Tennison –Malek protocol

alexandrossfakianakis shared this article with you from Inoreader Primary cheilorhinoseptoplasty using the Talmant protocol in unilateral complete cleft lip: functional and aesthetic results on nasal correction and comparison with the Tennison –Malek protocol Via International Journal of Oral and Maxillofacial Surgery via MedWorm.com Many surgical procedures used to treat patients with unilateral complete cleft lip do not include a complete primary rhinoseptoplasty, which is delayed until the end of growth as part of secondary surgery. Primary cheilorhinoseptoplasty using the Talmant technique has been performed at Lapeyronie University Hospital, Montpellier for 15 years. This retrospective study evaluated and compared the functional and aesthetic results obtained in such patients at 4 –6 years after surgery with those obtained without primary rhinoseptoplasty in patients undergoing the Tennison–Malek technique. (Source: International Journal of Oral and Maxillofacial Surgery) View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Rivaroxaban population pharmacokinetic and pharmacodynamic modeling

alexandrossfakianakis shared this article with you from Inoreader Rivaroxaban population pharmacokinetic and pharmacodynamic modeling in Iranian patients Via Journal of Clinical Pharmacy and Therapeutics A population pharmacokinetic/pharmacodynamic (PKPD) model of rivaroxaban was established in Iranian patients. The model consisted of a one-compartment pharmacokinetic model and a direct link linear equation that described the relationship of rivaroxaban concentration with both prothrombin and activated partial thromboplastin times. The selected model for anti-factor Xa activity consisted of a direct link inhibitory E max model with Hill coefficient. Significant differences were seen in the PKPD model parameters in Iranian patients compared to the values reported in other populations. Abstract What is Known and Objective Although predictable pharmacokinetic and pharmacodynamic of rivaroxaban allow fixed dosing regimens without routine coagulation monitoring, there is still the necessity to monitor and predict the effects of rivaroxaban in specific conditions and different populations. The current study was designed and conducted to analyze the rivaroxaban population pharmacokinetics in Iranian patients and establish a pharmacokinetic/pharmacodynamic model to predict the relationship between rivaroxaban concentration and its anticoagulant activity. Methods A sequential nonlinear mixed effect pharmacokinetic/pharmacodynamic modeling method was used to establish the relation between rivaroxaban concentration and anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time (aPTT) as pharmacodynamic biomarkers in a population of sixty-nine Iranian patients under treatment with oral rivaroxaban. Rivaroxaban plasma concentration was quantified by a validated high-performance liquid chromatography-tandem mass spectrometry. Results and Discussion The typical population values (inter-individual variability%) of the oral volume of distribution and clearance for a one-compartment model were 61.2 L (21%) and 3.68 L·h−1 (61%), respectively. Creatinine clearance and Child-Turcotte-Pugh score were found to affect the clearance. A direct link linear structural model best fitted the data for both prothrombin time and aPTT. The baseline estimates of aPTT and prothrombin time in the population were 35.0 (15%) and 12.6 (2%) seconds, respectively. The slope of the relationship between apTT, prothrombin time, and rivaroxaban concentration was 0.033 (28%) and 0.018 (54%) s·ml·ng−1, respectively. The selected model for anti-factor Xa activity consisted of a direct link inhibitory E max model with Hill coefficient. The maximum level of inhibition (E max) was 4 IU·ml−1. The concentration of rivaroxaban producing 50% of the maximum inhibitory effect (EC50) was 180 (24%) ng·ml−1, and Hill coefficient (γ) was 1.44 (108%). No covariates showed a statistically significant effect on PT and activated partial thromboplastin time prolonging properties and anti-factor Xa activity. What is New and Conclusion Our results confirmed that pharmacokinetic/pharmacodynamic models similar to those of the other studies describe the relationship between the rivaroxaban concentration and its anticoagulant effect in Iranian patients. However, considerable differences were observed in the parameters of the pharmacodynamics–pharmacokinetic models with the results of other reports that can explain the unpredictable effects of rivaroxaban in some patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pharmacokinetics, safety and efficacy of intra‐articular non‐steroidal anti‐inflammatory drug injections for the treatment of osteoarthritis: A narrative review

alexandrossfakianakis shared this article with you from Inoreader Pharmacokinetics, safety and efficacy of intra‐articular non‐steroidal anti‐inflammatory drug injections for the treatment of osteoarthritis: A narrative review Via Journal of Clinical Pharmacy and Therapeutics We provide a comprehensive review on intra-articular (IA) non-steroidal anti-inflammatory drug (NSAID) injections for the treatment of osteoarthritis (OA). We found that single doses of IA NSAIDs provided far less total systemic and synovial exposure compared to a one week course of oral NSAIDs, but maximum concentrations to the synovium with IA administration were much higher. Further, single IA NSAID injections appeared to be safe and efficacious compared to courses of oral NSAIDs or single IA corticosteroids in either small animals, large animals or humans. Further research must be conducted, however, IA NSAIDs could be used as an alternative or adjunct therapy to treat OA related pain, especially for patients that are high risk for corticosteroid related adverse effects. Abstract What is known and Objective Osteoarthritis (OA) is a common cause of joint disease and activity limitation in adults. Common therapies to treat OA-related pain are oral and topical non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular (IA) corticosteroids. However, prolonged courses of oral NSAIDs are associated with systemic adverse effects and repeat IA corticosteroid injections may cause cartilage degeneration. IA NSAIDs may be an alternative therapy possibly minimizing systemic side effects while maintaining efficacy. Therefore, we sought to summarize the pharmacokinetics, safety and efficacy of IA NSAIDs to help providers make a more informed decision on the use of IA NSAIDs. Methods We searched the National Library of Medicine Database with terms "intraarticular and nsaid", yielding 1032 results. Only traditional formulations of NSAIDs were considered for inclusion. Animal studies were included if animals were healthy or if the method of arthritis induction was a reasonable model of osteoarthritis. Human studies were included if humans were healthy or if the primary disease studied was osteoarthritis of a large joint. Of 1032 results, 31 research articles met the inclusion criteria and were summarized in this review. Results and Discussion We found that single doses of IA NSAIDs provided far less total systemic and synovial exposure compared to a one week course of oral NSAIDs, but maximum concentrations to the synovium with IA administration were much higher. IA NSAIDs had an excellent safety profile in small animals, large animals and humans, although these injections were associated with non-specific cartilage inflammation in healthy animals. In animal models, IA NSAIDs had similar efficacy to PO NSAIDs in treating OA-related pain. In humans, IA NSAIDs had similar efficacy to PO NSAIDS and IA corticosteroids in treating OA-related pain; however, many trials did not have a placebo control and outcome measures were heterogeneous. What is new and Conclusion Overall, single doses of IA NSAIDs appear safe and efficacious across animals and humans. The optimal use of IA NSAIDs is still to be determined and further research is needed. However IA NSAIDs may be an additional beneficial therapy to treat OA-related pain. Potential uses may be to augment IA corticosteroids injections, to interrupt multiple IA corticosteroid injections or as an alternative in patients that are high risk for corticosteroid-related adverse events. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Expression of PINK1 and Parkin in human apical periodontitis

alexandrossfakianakis shared this article with you from Inoreader Expression of PINK1 and Parkin in human apical periodontitis Via International Endodontic Journal Abstract Aim PTEN-induced putative kinase 1 (PINK1) and Parkin E3 ubiquitin-protein ligase (Parkin) are critical for immune and inflammatory regulation in health and disease. PINK1 and Parkin have been confirmed to be involved in the progression of apical periodontitis by affecting mitophagy-related osteoblast apoptosis; however, the expression of PINK1 and Parkin in macrophages, one of the most important cells in apical periodontitis, remains unknown. This study aimed to investigate the expression of PINK1 and Parkin in human apical periodontitis lesions, as well as their possible localization in macrophages. Methodology Thirty-seven human periapical tissues, including periapical granulomas (PGs, n=12), radicular cysts (RCs, n=11), and healthy gingival tissues (n=14) were examined. The inflammatory infiltrates of lesions were evaluated by haemotoxylin staining, and the expression of PINK1 and Parkin was detected by immunohistochemistry. Double immunofluorescence was used to explore the colocalization of microtubule-associated protein 1 light chain 3 (LC3) and TOMM20, as well as the localization of PINK1 and Parkin, in macrophages of human apical periodontitis lesions. The ultrastructural morphology of mitochondria in human apical periodontitis lesions was visualized by transmission electron microscopy (TEM). Data were analyzed by one-way ANOVA with Student-Newman-Keul's test and Mann–Whitney test. P < 0.05 was considered statistically significant. Results Immunohistochemistry demonstrated a significantly higher expression of PINK1 and Parkin proteins in human apical periodontitis lesions than in healthy gingival tissues (P < 0.0001), but no significant difference was demonstrated between PGs and RCs (P > 0.05). The higher expression of LC3 and the presence of more LC3-TOMM20 double-positive cells were also observed in human apical periodontitis. Double-labeling analysis of PINK1, Parkin, and LC3 with CD68 indicated that macrophage mitophagy might be present in the progression of human apical periodontitis. Finally, the results of TEM morphological analysis revealed the appearance of double-membraned mitophagosomes and vacuolated mitochondria in macrophage-like cells of apical periodontitis lesions. Conclusions Our findings indicated that PINK1 and Parkin proteins were highly expressed in clinical apical periodontitis lesions. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.