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1.
Surg Neurol Int ; 15: 204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974537

RESUMO

Background: Cranioplasty has been useful in treating the symptoms associated with the "Sunken skin flap syndrome" post decompressive craniectomy, for which various mechanisms have been proposed. In this study, we aim to assess the changes in the cerebral blood flow and intracranial cerebrospinal fluid (CSF) dynamics post cranioplasty and correlate with the improvement in the neurocognitive status. Methods: Computed tomography perfusion and cine magnetic resonance imaging studies were done to study the changes in cerebral perfusion and CSF flow dynamics postcranioplasty. The cognitive status was assessed using Montreal cognitive assessment, mini-mental state examination, and frontal assessment battery scores in the preoperative period and at 1 and 6 months follow-up. Results: There was a significant change in cognitive status postcranioplasty, both at 1 and 6 months follow-up, which was associated with a significant improvement in cerebral blood flow, decreased mean transit time, and improvement in the mean and peak CSF flow velocities at the foramen of Magendie and aqueduct of Sylvius. Conclusion: Cranioplasty leads to a marked improvement in cerebral hemodynamics, which is more significant on the ipsilateral side. It also leads to increased CSF turnover and improved CSF circulation. Improved cerebral perfusion and, more importantly, CSF dynamics may be responsible for the demonstrable improvement in the neurocognition in the postcranioplasty period.

2.
Acta Neurol Belg ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669002

RESUMO

Pediatric brain tumors are the primary cause of death in children with cancer. Diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG) are frequently unresectable due to their difficult access location, and 5-year survival remains less than 20%. Despite significant advances in tumor biology and genetics, treatment options remain limited and ineffective. Immunotherapy using T cells with a chimeric antigen receptor (CAR) that has been genetically engineered is quickly emerging as a new treatment option for these patients. High levels of expression were detected for both disialoganglioside (GD2) and B7-H3 in pediatric DMG/DIPG. Numerous studies have been conducted in recent years employing various generations of GD2-CAR T cells. The two most prevalent adverse effects found with this therapy are cytokine release syndrome, which varies in severity from mild constitutional symptoms to a high-grade disease associated with potentially fatal multi-organ failure, and neurotoxicity, known as CAR T-cell-related encephalopathy syndrome. During the acute phase of anticancer action, peri-tumoral neuro-inflammation might cause deadly hydrocephalus. The initial results of clinical trials show that the outcomes are not highly encouraging as B cell malignancies and myelomas. In vivo research on CAR T-cell therapy for DIPG has yielded encouraging results, but in human trials, the early results have shown potentially fatal side effects and very modest, but fleeting improvements. Solid tumors present a hindrance to CAR T-cell therapy because of the antigenic dilemma and the strong immune-suppressing tumor microenvironment.

3.
Cancer ; 130(7): 1137-1146, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38105655

RESUMO

BACKGROUND: Depression is common in patients with cancer and is associated with lower treatment adherence and reduced quality of life. Antidepressants and psychotherapy have limited success in improving depression among patients with cancer. This study explored the safety, feasibility, and efficacy of psilocybin-assisted therapy in patients with cancer and major depressive disorder. METHODS: This phase 2, open-label trial enrolled patients with curable and noncurable cancer and major depressive disorder at a single community oncology practice site. A single 25-mg dose of psilocybin was administered simultaneously to cohorts of three to four participants with individual (4.25 hours in 1:1 therapist-to-patient ratio) and group therapeutic support (3.75 hours) before, during, and after psilocybin administration. Outcomes included depression severity, anxiety, pain, demoralization, and disability. RESULTS: Thirty participants completed the study. No psilocybin-related serious adverse events occurred; treatment-related adverse events (e.g., nausea, headache) were generally mild and expected. There were no laboratory or electrocardiogram abnormalities. No suicidality was reported. Efficacy was suggested with a robust reduction in depression severity scores from baseline to posttreatment of 19.1 points (95% CI, 22.3 to -16.0; p < .0001) by week 8. Eighty percent of participants demonstrated a sustained response to psilocybin treatment; 50% showed full remission of depressive symptoms at week 1, which was sustained for 8 weeks. CONCLUSIONS: Psilocybin-assisted therapy in group cohort administration was safe and feasible in patients with cancer and depression. Efficacy was suggested based on clinically meaningful reductions in depressive symptoms. The novel, group-oriented format, compact delivery time, community cancer center setting, and one-to-one therapist-to-patient ratio could also add to therapeutic gains and efficiency of administration. TRIAL REGISTRATION: NCT04593563. PLAIN LANGUAGE SUMMARY: Depression is common in patients with cancer and associated with lower treatment adherence, reduced quality of life, and limited response to antidepressants and psychotherapy. We conducted a phase 2 trial to study a single dose of psilocybin administered in a group therapy setting with one-to-one therapist-to-participant psychological support to patients with curable and noncurable cancer and major depressive disorder. Findings of the study showed safety (no treatment-related serious adverse events or suicidality) with psilocybin and suggested efficacy, with a significant reduction in depression severity scores from baseline to posttreatment. Further investigation is warranted.


Assuntos
Transtorno Depressivo Maior , Neoplasias , Psicoterapia de Grupo , Humanos , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Psilocibina/efeitos adversos , Qualidade de Vida
4.
Cancer ; 130(7): 1147-1157, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38105653

RESUMO

BACKGROUND: The present study explored the acceptability of psilocybin-assisted group therapy from the perspective of patients with cancer and depression who participated in a clinical trial assessing the safety and efficacy of this novel intervention. METHODS: Guided by the conceptual framework of acceptability, the authors conducted semi-structured interviews with participants of the psilocybin trial. Data were analyzed using template and thematic analyses. RESULTS: Participants' (n = 28) perspectives on the acceptability of the group and simultaneous sessions was generally positive, both in terms of safety and efficacy: first, the groups contributed to increase participants' sense of safety and preparedness as they were engaging in the therapy; and second, the groups fostered a sense of connection and of belonging, which served to enrich and deepen the meaning of participants' experience, ultimately opening a dimension of self-transcendence and compassion. Other subthemes related to factors influencing the acceptability of the group approach included: 1) the importance of the therapeutic framework, 2) the complementary value of individual sessions, 3) disruptive factors related to the group and/or simultaneous setting, and 4) opportunities and challenges related to group size and how to structure interactions. CONCLUSIONS: This study enhances understanding of what promotes acceptability of the psilocybin-assisted therapy group model for the treatment of MDD in cancer patients. PLAIN LANGUAGE SUMMARY: We conducted exit interviews with participants of a phase 2 trial of psilocybin-assisted therapy (PAT) conducted in a community cancer center, to assess the acceptability of a novel psilocybin delivery model combining simultaneous individual therapy and group sessions. Our findings support the acceptability of this intervention and suggest that in addition to being feasible, it might also enhance participants' perceived safety and efficacy compared to uniquely individual or group delivery models of PAT. Our analysis highlights critical factors conditioning acceptability and suggests new ways PAT may be scaled and integrated into cancer care.


Assuntos
Transtorno Depressivo Maior , Neoplasias , Psicoterapia de Grupo , Humanos , Psilocibina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Psicoterapia , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente
5.
Front Psychiatry ; 14: 1293243, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38125286

RESUMO

Objective: To compare group and individual psychedelic-assisted therapy in terms of clinician time, costs and patient access. Methods: Using 2023 data from two group therapy trial sites, one using 3,4-Methylenedioxymethamphetamine (MDMA) to treat posttraumatic stress disorder (PTSD), and one using psilocybin to treat major depressive disorder (MDD), we compared overall variable costs, clinician costs and clinician time required by therapy protocols utilizing groups versus individual patient therapy. Using published literature, we estimated the prevalence of adults with PTSD and MDD eligible for treatment with psychedelic therapy and projected the savings in time and cost required to treat these prevalent cases. Results: Group therapy saved 50.9% of clinician costs for MDMA-PTSD and 34.7% for psilocybin-MDD, or $3,467 and $981 per patient, respectively. To treat all eligible PTSD and MDD patients in the U.S. in 10 years with group therapy, 6,711 fewer full-time equivalent (FTE) clinicians for MDMA-PTSD and 1,159 fewer for FTE clinicians for psilocybin-MDD would be needed, saving up to $10.3 billion and $2.0 billion respectively, discounted at 3% annually. Conclusion: Adopting group therapy protocols where feasible would significantly reduce the cost of psychedelic-assisted therapies. By enhancing the number of patients served per clinician, group therapy could also ameliorate the anticipated shortage of appropriately trained clinicians, thereby accelerating access to these promising new therapies.

6.
J Palliat Med ; 26(12): 1702-1708, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37590474

RESUMO

Context: Measuring therapeutic connection during psilocybin-assisted therapy is essential to understand underlying mechanisms, inform training, and guide quality improvement. Purpose: To evaluate the feasibility of directly observing indicators of therapeutic connection during psilocybin administration encounters. Methods: We evaluated audio and video data from a recent clinical trial for observable expressions of therapeutic connection as defined in proposed best-practice competencies (i.e., empathic abiding presence and interpersonal grounding). We selected the first four 8-hour encounters involving unique participants, therapists, and gender pairs. Each video was independently coded by three members of an interprofessional six-person team. Using a structured checklist, coders recorded start-stop times, the audible (i.e., speech prosody or words) and visible (i.e., body movements, eye gaze, and touch) cues marking the event, and the qualities of the interaction (e.g., expression of awe, trust, distress, and calmness). We assessed feasibility by observing the frequency, distribution, and overlap of cues and qualities coders used to identify and define moments of therapeutic connection. Results: Among the 2074 minutes of video, coders recorded 372 moments of therapeutic connection. Eighty-three percent were identified by at least two coders and 41% by all three. Coders used a combination of audible and visual cues to identify therapeutic connection in 51% of observed events (190/372). Both the cues and qualities of therapeutic connection expressions varied over the course of psilocybin temporal effects on states of consciousness. Conclusion: Direct observation of therapeutic human connection is feasible, sensitive to changes in states of consciousness and requires evaluation of audible and visual data.


Assuntos
Emoções , Psilocibina , Humanos , Estudos de Viabilidade , Estado de Consciência
7.
JAMA Oncol ; 9(6): 864-866, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37052904

RESUMO

This nonrandomized controlled trial used a 1-to-1 therapist-to-patient ratio to administer psilocybin to groups of patients with cancer who were diagnosed with major depression disorder to create a scalable, rapidly effective depression treatment.


Assuntos
Transtorno Depressivo Maior , Neoplasias , Humanos , Psilocibina/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Pacientes
8.
Indian J Surg Oncol ; 14(1): 204-207, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36891450

RESUMO

CD44 + /CD24 - phenotype has been associated with stem cell-like characteristics with enhanced invasive properties, radiation resistance, and with distinct genetic profiles suggesting a correlation to adverse prognosis in western literature. The aim of this study was to study CD44 + /CD24 - phenotype as an adverse prognostic marker in Indian breast cancer patients. N = 61 breast cancer patients included in a tertiary care facility in India were evaluated for receptor studies (estrogen receptor ER, progesterone receptor PR, Herceptin antibody Her2 neu receptor, CD44 & CD24 stem cell markers). CD44 + /CD24 - phenotype was statistically related to adverse factors like estrogen and progesterone receptors non-expression, her 2 neu expression, and triple-negative breast cancer. Of the 39 patients with ER-ve status, 33 (84.6%) were found to have CD44 + /CD24 - phenotype and 82.5% of all the CD 44 + /CD24 - patients were ER negative (p = 0.001). Thirty-four (75.5%) of the PR-ve patients showed the CD44 + /CD24 - phenotype, and of all the CD 44 + /CD24 - patients, 85% of were PR negative (p = 0.006). Thirty-six (75%) of Her-2-Neu + ve were CD44 + /CD24 - . Approximately 90% of the Her 2 Neu patients expressed CD44 + /CD24 - and 76.9% of all the triple-negative patients were found to be CD44 + /CD24 - expression (p = 0.001). CD44 + /CD24 - had a significant association with adverse prognostic factors like stage of disease, hormonal receptor status, and molecular subtypes in Indian breast cancer patients like the Western data.

10.
World Neurosurg ; 171: e447-e455, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36528317

RESUMO

PURPOSE: In children, epidural hematomas (EDHs) constitute around 2% to 3% of all head traumas. The aim of this study is to compare the manifestation, prognostic factors, and outcome of surgically treated supratentorial with infratentorial EDHs in pediatric patients. METHODS: This is a hospital-based single-center, retrospective study of 350 pediatric patients admitted between January 2016 and December 2021. All pediatric patients to 18 years of age with posttraumatic EDHs with or without other intracranial/extracranial injuries who underwent surgical evacuation were included in the study. Posttraumatic EDHs treated conservatively during the hospital stay and any EDH unrelated to head trauma were excluded. Glasgow Outcome Scale (GOS) score was used to assess functional outcomes at discharge. The status of the patients at 3-month follow-up was assessed by using the pediatric version of the Glasgow Outcome Scale-Extended (GOS-E Peds) Score. RESULTS: Out of 350 patients, 310 had supratentorial EDH and 40 had infratentorial EDH. In supratentorial EDH, the volume of hematoma, mass effect, and the time interval between trauma and surgery correlated with functional outcome (GOS) at discharge. Anisocoria, hypotension, and intradural injury were associated with functional as well as behavioral outcomes (GOS-E Peds) in the supratentorial EDH group. The severity of the injury was correlated with the functional and behavioral outcomes in both groups. CONCLUSIONS: Infratentorial EDH has better clinical outcomes than supratentorial EDH in surgically treated pediatric patients. The most significant and consistent factor influencing the outcome in both groups was the Glasgow Coma Score on admission.


Assuntos
Traumatismos Craniocerebrais , Hematoma Epidural Craniano , Hematoma Epidural Espinal , Criança , Humanos , Prognóstico , Estudos Retrospectivos , Países em Desenvolvimento , Hematoma Epidural Craniano/cirurgia , Hematoma Epidural Espinal/complicações , Traumatismos Craniocerebrais/complicações , Escala de Coma de Glasgow
11.
J Affect Disord ; 323: 592-597, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36513161

RESUMO

BACKGROUND: While psychedelics have been shown to improve psycho-spiritual well-being, the underlying elements of this change are not well-characterized. The NIH-HEALS posits that psycho-social-spiritual change occurs through the factors of Connection, Reflection & Introspection, and Trust & Acceptance. This study aimed to evaluate the changes in NIH-HEALS scores in a cancer population with major depressive disorder undergoing psilocybin-assisted therapy. METHODS: In this Phase II, single-center, open label trial, 30 cancer patients with major depressive disorder received a fixed dose of 25 mg of psilocybin. Participants underwent group preparation sessions, simultaneous psilocybin treatment administered in adjacent rooms, and group integration sessions, along with individual care. The NIH-HEALS, a self-administered, 35-item measure of psycho-social spiritual healing was completed at baseline and post-treatment at day 1, week 1, week 3, and week 8 following psilocybin therapy. RESULTS: NIH-HEALS scores, representing psycho-social-spiritual wellbeing, improved in response to psilocybin treatment (p < 0.001). All three factors of the NIH-HEALS (Connection, Reflection & Introspection, and Trust & Acceptance) demonstrated positive change by 12.7 %, 7.7 %, and 22.4 %, respectively. These effects were apparent at all study time points and were sustained up to the last study interval at 8 weeks (p < 0.001). LIMITATIONS: The study lacks a control group, relies on a self-report measure, and uses a relatively small sample size with limited diversity that restricts generalizability. CONCLUSIONS: Findings suggest that psilocybin-assisted therapy facilitates psycho-social-spiritual growth as measured by the NIH-HEALS and its three factors. This supports the factors of Connection, Reflection & Introspection, and Trust & Acceptance as underlying elements for psycho-social-spiritual healing in cancer patients, and validates the use of the NIH-HEALS within psychedelic research.


Assuntos
Transtorno Depressivo Maior , Alucinógenos , Neoplasias , Humanos , Psilocibina/farmacologia , Psilocibina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Alucinógenos/farmacologia , Alucinógenos/uso terapêutico , Autorrelato , Neoplasias/tratamento farmacológico
12.
Inf Syst Front ; 25(2): 431-450, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36061586

RESUMO

This research contributes to the knowledge of how Information Systems (IS) researchers can iteratively intervene with practitioners to co-create instructional programs with a framework designed for fast-paced, rapidly changing IS fields such as cybersecurity. We demonstrate how complex fields, such as cybersecurity, have the need for a skilled workforce that continues to rapidly outpace supply from universities. IS researchers partnering with practitioners can use this research as an exemplar of a method to design, build, and evaluate these innovative co-curricular IS programs. Moreover, we find these co-curricular IS programs are essential to upskilling students, integrating training on the latest tools, systems, and processes in these rapidly evolving disciplines. Supplementary Information: The online version contains supplementary material available at 10.1007/s10796-022-10332-y.

13.
Turk Neurosurg ; 32(5): 709-719, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35929029

RESUMO

AIM: To evaluate all serum biomarkers in sports-related concussion injury (SRC) to determine diagnostic validity, changes with symptom severity, and return to play, as well as detect early changes in serum concentration. MATERIAL AND METHODS: Studies were searched in various electronic databases (MEDLINE/PubMed, EMBASE, CINAHL, Scopus and Cochrane databases) from their commencement to May 2021. Studies were included if athletes aged 12 years and older were diagnosed with a concussion injury and evaluated using serum biomarkers. Studies including athletes with injuries other than concussion injuries were excluded. Articles with fewer than 20 concussed athletes were excluded. There were 1782 articles identified. RESULTS: After exclusion a total of 17 articles qualified for systematic review. S100 calcium binding protein ? (S-100?) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) showed promising results in distinguishing concussed athletes from contact sports and non-athlete controls. Most of the serum biomarkers increased within 6 hours of SRC. Serum neurofilament light protein (NFL) positively correlated with the severity of post-concussion symptoms. NFL, tau and Interleukins (IL-1 Ra and IL-6) have the potential to determine return to play. CONCLUSION: Serum biomarker measurement is an objective tool that aids in early diagnosis and predicts the severity and prognosis of injury.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Traumatismos em Atletas/diagnóstico , Biomarcadores , Concussão Encefálica/diagnóstico , Proteínas de Ligação ao Cálcio , Humanos , Hidrolases , Interleucina-1 , Interleucina-6 , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Ubiquitinas
14.
World Neurosurg ; 167: e620-e628, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36007770

RESUMO

OBJECTIVE: To evaluate the usefulness and degree of perfusion abnormalities in pediatric head injury patients by using computed tomography perfusion (CTP) and to assess its co-relation with neurologic outcome based on Glasgow Outcome Scale Extended Pediatric revision (GOSE-P). METHODS: Prospective evaluation of pediatric head injury patients who were taken for CTP after admission and then on discharge. We evaluated 5 regions of interest: orbitofrontal cortex, internal capsule, thalamus, caudate nucleus, and sensorimotor cortex for cerebral blood perfusion. The patient's clinical and radiologic findings were analyzed, correlated with cerebral blood flow (CBF) and MTT (mean transient time), and the outcome assessed using the GOSE-P scale on 3-month follow-up. RESULTS: Both CBF and MTT showed a correlation with the GOSE-P scale. In mild head injury patients, the Pearson correlation of GOSE-P with mean CBF and mean MTT was -0.11 and 0.56, respectively (P < 0.05) in the sensorimotor cortex; in moderate head injury patients the Pearson correlation of GOSE-P with mean CBF in the caudate nucleus and mean MTT in the internal capsule was -0.32 and 0.36, respectively (P < 0.05); and in severe head injury patients, the Pearson correlation of GOSE-P with mean CBF and mean MTT was -0.78 and 0.56, respectively (P < 0.05) in the caudate nucleus, which had the highest Pearson co-relation among the regions studied. CONCLUSIONS: We conclude that CBF and MTT are 2 important radiologic parameters that can be used as prognostic indicators in pediatric head injury patients.


Assuntos
Traumatismos Craniocerebrais , Tomografia Computadorizada por Raios X , Humanos , Criança , Tomografia Computadorizada por Raios X/métodos , Perfusão , Prognóstico , Circulação Cerebrovascular/fisiologia
15.
J Laparoendosc Adv Surg Tech A ; 32(5): 556-560, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35394355

RESUMO

Introduction: Radical minimal access cancer surgery has demonstrated similar outcomes as open surgery of late, but with less morbidity, improving the quality of life especially in patients with colorectal cancer. Initial retrocolic endoscopic tunnel approach (IRETA) has been described in the literature by Palanivelu et al. as a laparoscopic technique for radical resection of malignant right colonic lesions (MRCL) following the modified concept of medial to lateral dissection. In this work, the authors present their experience of this ergonomic surgical technique. Materials and Methods: To begin with, retrocolic dissection was carried out to free and dissect the ascending colon up to hepatic flexure with the reflection of the peritoneum over the right colon along the white line of Toldt with abdominal wall kept intact initially to sustain intracorporeal specimen steadiness. Subsequently, the specimen is lifted medially in a distinct lymphovascular sheath, leading to high ligation of ileocolic, right colic, and the right branch of the middle colic vein with a consequent definite en bloc thorough removal of the lesion. The specimen was delivered through a transumbilical incision. Results: Ten patients (age 45.4 ± 5.6 years) underwent resection by the IRETA technique with a mean operating time of 185 ± 30 minutes and blood loss of 90 ± 20 mL. Mean hospital stay was 6 days. R0 surgical resection was achieved in all patients with proper marginal clearance. Ninety percent had adequate lymph nodal resection. One patient had an intraoperative complication and n = 3 patients developed postoperative ileus. Adjuvant chemotherapy was given and there is no recurrence on 28 months of average follow-up. Conclusion: With the increasing use of laparoscopic surgery for the management of colorectal cancers, the IRETA technique appears to be an ergonomic and oncologically robust procedure for the removal of MRCL. The presented data set needs to be increased with at least 5 years of follow-up to establish long-term surgical outcomes.


Assuntos
Cólica , Neoplasias do Colo , Laparoscopia , Mesocolo , Adulto , Colectomia/métodos , Cólica/cirurgia , Colo Ascendente/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Ergonomia , Hospitais , Humanos , Laparoscopia/métodos , Mesocolo/cirurgia , Pessoa de Meia-Idade , Qualidade de Vida
16.
J Psychopharmacol ; 36(1): 6-11, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33888025

RESUMO

Favourable regulatory assessments, liberal policy changes, new research centres and substantial commercial investment signal that psychedelic therapy is making a major comeback. Positive findings from modern trials are catalysing developments, but it is questionable whether current confirmatory trials are sufficient for advancing our understanding of safety and best practice. Here we suggest supplementing traditional confirmatory trials with pragmatic trials, real-world data initiatives and digital health solutions to better support the discovery of optimal and personalised treatment protocols and parameters. These recommendations are intended to help support the development of safe, effective and cost-efficient psychedelic therapy, which, given its history, is vulnerable to excesses of hype and regulation.


Assuntos
Pesquisa Biomédica , Tecnologia Digital , Desenvolvimento de Medicamentos/métodos , Alucinógenos/farmacologia , Pesquisa Biomédica/métodos , Humanos
18.
Cancer Med ; 11(2): 358-370, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34921527

RESUMO

Filanesib is a first-in-class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose-escalation phase results. This multicenter study included first a dose-escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose-expansion phase using the maximum tolerated doses. In the dose-expansion phase, 28 patients were evaluable for safety and efficacy. The most common grade ≥3 adverse events were neutropenia (21%) and anemia (18%), which were noncumulative and reversible, and hypertension (18%). The overall response rate was 43% with median duration of response not yet reached (range, 2.8-23.7+ months) with median follow-up of 6.3 months. A post hoc analysis incorporated 29 dose-escalation phase patients who received therapeutic filanesib doses, with an overall response rate of 39% and median duration of response of 18.0 months among the 57 total patients with median progression-free survival of 8.5 months. Notably, the PFS of high risk patients was comparable at 8.5 months, driven by the patients with 1q21 gain, characterized by increased MCL-1 expression, with a PFS of 9.1 months versus 3.5 months for the remainder of high risk patients. Patients with t(11;14) also had an encouraging PFS of 15.0 months. The combination of filanesib, bortezomib, and dexamethasone continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Tiadiazóis/administração & dosagem , Adulto , Idoso , Aberrações Cromossômicas , Cromossomos Humanos Par 1/genética , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão
19.
Front Pharmacol ; 12: 699054, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675801

RESUMO

With the emergence and spread of global antibiotic resistance and the need for searching safer alternatives, there has been resurgence in exploring the use of bacteriophages in the treatment of bacterial infections referred as phage therapy. Although modern phage therapy has come a long way as demonstrated by numerous efficacy studies but the fact remains that till date, phage therapy has not received regulatory approval for human use (except for compassionate use).Thus, to hit the clinical market, the roadblocks need to be seriously addressed and gaps mended with modern solution based technologies. Nanotechnology represents one such ideal and powerful tool for overcoming the pharmacological barriers (low stability, poor in-vivo retention, targeted delivery, neutralisation by immune system etc.) of administered phage preparations.In literature, there are many review articles on nanotechnology and bacteriophages but these are primarily focussed on highlighting the use of lytic and temperate phages in different fields of nano-medicine such as nanoprobes, nanosensors, cancer diagnostics, cancer cell targeting, drug delivery through phage receptors, phage display etc. Reviews specifically focused on the use of nanotechnology driven techniques strictly to improve phage therapy are however limited. Moreover, these review if present have primarily focussed on discussing encapsulation as a primary method for improving the stability and retention of phage(s) in the body.With new advances made in the field of nanotechnology, approaches extend from mere encapsulation to recently adopted newer strategies. The present review gives a detailed insight into the more recent strategies which include 1) use of lipid based nano-carriers (liposomes, transfersomes etc.) 2) adopting microfluidic based approach, surface modification methods to further enhance the efficiency and stability of phage loaded liposomes 3) Nano- emulsification approach with integration of microfluidics for producing multiple emulsions (suitable for phage cocktails) with unique control over size, shape and drop morphology 4) Phage loaded nanofibers produced by electro-spinning and advanced core shell nanofibers for immediate, biphasic and delayed release systems and 5) Smart release drug delivery platforms that allow superior control over dosing and phage release as and when required. All these new advances are aimed at creating a suitable housing system for therapeutic bacteriophage preparations while targeting the multiple issues of phage therapy i.e., improving phage stability and titers, improving in-vivo retention times, acting as suitable delivery systems for sustained release at target site of infection, improved penetration into biofilms and protection from immune cell attack. The present review thus aims at giving a complete insight into the recent advances (2010 onwards) related to various nanotechnology based approaches to address the issues pertaining to phage therapy. This is essential for improving the overall therapeutic index and success of phage therapy for future clinical approval.

20.
Clin Pathol ; 14: 2632010X211033840, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368763

RESUMO

Skin and Adnexal tumours are a group of benign and malignant tumours whose basic diagnosis relies on histopathology. A single tumour may show more than 1 appendageal differentiation. Morphologic distinction between benign and its malignant counterpart is of utmost importance as it affects the treatment and prognosis of patient. We have described 3 cases who presented in our university hospital, in which final resection pathological diagnosis differed from initial core biopsy interpretation. The authors have made an attempt to provide a brief overview of diagnostic overlap existing between nodular hidradenocarcinoma and tumours of clear cell histology. Salient morphologic features differentiating cylindroma or trichilemmal carcinoma from squamous cell carcinoma have also been discussed. Final diagnosis is paramount for adjuvant management and prognostication of the patient in a clinical setting.

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