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1.
Artigo em Inglês | MEDLINE | ID: mdl-38953646

RESUMO

BACKGROUND AND OBJECTIVES: In cases where dumbbell-shaped cervical schwannoma encases the vertebral artery (VA), there is a risk of VA injury during surgery. The objective of this study is to propose a strategy for preserving the VA during the surgical excision of tumors adjacent to the VA through the utilization of anatomic layers. METHODS: A retrospective analysis was conducted on 37 patients who underwent surgery for dumbbell-shaped cervical schwannoma with contacting VA from January 2004 to July 2023. The VA encasement group consisted of 12 patients, and the VA nonencasement group included 25 patients. RESULTS: The perineurium acted as a protective barrier from direct VA exposure or injury during surgery. However, in the VA encasement group, 1 patient was unable to preserve the perineurium while removing a tumor adjacent to the VA, resulting in VA injury. The patient had the intact dominant VA on the opposite side, and there were no new neurological deficits or infarctions after the surgery. Gross total resection was achieved in 25 patients (67.6%), while residual tumor was confirmed in 12 patients (32.4%). Four patients (33.3% of 12 patients) underwent reoperation because of the regrowth of the residual tumor within the neural foramen. In the case of the 8 patients (66.7% of 12 patients) whose residual tumor was located outside the neural foramen, no regrowth was observed, and there was no recurrence of the tumor within the remaining perineurium after total resection. CONCLUSION: In conclusion, when resecting a dumbbell-shaped cervical schwannoma contacting VA, subperineurium dissection prevents VA injury because the perineurium acts as a protective barrier.

2.
PLoS One ; 19(7): e0305694, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985701

RESUMO

OBJECTIVES: Intraoperative ultrasonography (IOUS) offers the advantage of providing real-time imaging features, yet it is not generally used. This study aims to discuss the benefits of utilizing IOUS in spinal cord surgery and review related literature. MATERIALS AND METHODS: Patients who underwent spinal cord surgery utilizing IOUS at a single institution were retrospectively collected and analyzed to evaluate the benefits derived from the use of IOUS. RESULTS: A total of 43 consecutive patients were analyzed. Schwannoma was the most common tumor (35%), followed by cavernous angioma (23%) and ependymoma (16%). IOUS confirmed tumor extent and location before dura opening in 42 patients (97.7%). It was particularly helpful for myelotomy in deep-seated intramedullary lesions to minimize neural injury in 13 patients (31.0% of 42 patients). IOUS also detected residual or hidden lesions in 3 patients (7.0%) and verified the absence of hematoma post-tumor removal in 23 patients (53.5%). In 3 patients (7.0%), confirming no intradural lesions after removing extradural tumors avoided additional dural incisions. IOUS identified surrounding blood vessels and detected dural defects in one patient (2.3%) respectively. CONCLUSIONS: The IOUS can be a valuable tool for spinal cord surgery in identifying the exact location of the pathologic lesions, confirming the completeness of surgery, and minimizing the risk of neural and vascular injury in a real-time fashion.


Assuntos
Neoplasias da Medula Espinal , Medula Espinal , Ultrassonografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia/métodos , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia , Adolescente , Adulto Jovem , Neurilemoma/cirurgia , Neurilemoma/diagnóstico por imagem , Criança , Ependimoma/cirurgia , Ependimoma/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/efeitos adversos
3.
PLoS One ; 19(6): e0305128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861502

RESUMO

During the first year of the COVID-19 pandemic, the Republic of Korea (ROK) experienced three epidemic waves in February, August, and November 2020. These waves, combined with the overarching pandemic, significantly influenced trends in spinal surgery. This study aimed to investigate the trends in degenerative lumbar spinal surgery in ROK during the early COVID-19 pandemic, especially in relation to specific epidemic waves. Using the National Health Information Database in ROK, we identified all patients who underwent surgery for degenerative lumbar spinal diseases between January 1, 2019 and December 31, 2020. A joinpoint regression was used to assess temporal trends in spinal surgeries over the first year of the COVID-19 pandemic. The number of surgeries decreased following the first and second epidemic waves (p<0.01 and p = 0.34, respectively), but these were offset by compensatory increases later on (p<0.01 and p = 0.05, respectively). However, the third epidemic wave did not lead to a decrease in surgical volume, and the total number of surgeries remained comparable to the period before the pandemic. When compared to the pre-COVID-19 period, average LOH was reduced by 1 day during the COVID-19 period (p<0.01), while mean hospital costs increased significantly from 3,511 to 4,061 USD (p<0.01). Additionally, the transfer rate and the 30-day readmission rate significantly decreased (both p<0.01), while the reoperation rate remained stable (p = 0.36). Despite the impact of epidemic waves on monthly surgery numbers, a subsequent compensatory increase was observed, indicating that surgical care has adapted to the challenges of the pandemic. This adaptability, along with the stable total number of operations, highlights the potential for healthcare systems to continue elective spine surgery during public health crises with strategic resource allocation and patient triage. Policies should ensure that surgeries for degenerative spinal diseases, particularly those not requiring urgent care but crucial for patient quality of life, are not unnecessarily halted.


Assuntos
COVID-19 , Bases de Dados Factuais , Vértebras Lombares , Humanos , COVID-19/epidemiologia , República da Coreia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Vértebras Lombares/cirurgia , Idoso , Pandemias , Programas Nacionais de Saúde , SARS-CoV-2 , Adulto , Doenças da Coluna Vertebral/cirurgia , Doenças da Coluna Vertebral/epidemiologia
4.
JCO Oncol Pract ; : OP2300787, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739872

RESUMO

KRAS mutations are common driver oncogenes associated with the development of several solid tumors. KRAS oncogene has been considered a highly challenging target for drug development because of structural features, including the lack of deep groove on its catalytic unit. However, by leveraging cysteine residues, covalent KRAS inhibitors irreversibly trap KRAS G12C mutants in their inactive GDP-bound state. These agents have resulted in significant clinical responses among patients with KRAS G12C-mutant solid tumors, including patients with colorectal cancer (CRC). Other allele-specific inhibitors of KRAS oncogene and panKRAS and panRAS inhibitors are also currently being investigated in clinical trials. This review article overviews recent clinical progress on KRAS G12C targeting for the management of patients with KRAS G12C-mutant CRC and provides an update on other RAS targeting approaches. We also discuss the unique biological features of RAS-mutant CRC, which require the combination of KRAS inhibitors and anti-epidermal growth factor receptor therapy, and elaborate on resistance mechanisms and novel therapeutic avenues that may define future treatment paradigms of patients with RAS-mutant CRC.

5.
BMC Med Educ ; 24(1): 524, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730447

RESUMO

BACKGROUND: In recent years, the subspecialty of neuropalliative care has emerged with the goal of improving the quality of life of patients suffering from neurological disease, though gaps remain in neuropalliative care education and training. E-learning has been described as a way to deliver interactive and facilitated lower-cost learning to address global gaps in medical care. We describe here the development of a novel, international, hybrid, and asynchronous curriculum with both self-paced modules and class-based lectures on neuropalliative care topics designed for the neurologist interested in palliative care, the palliative care physician interested in caring for neurological patients, and any other physician or advanced care providers interested in neuropalliative care. METHODS: The course consisted of 12 modules, one per every four weeks, beginning July 2022. Each module is based on a case and relevant topics. Course content was divided into three streams (Neurology Basics, Palliative Care Basics, and Neuropalliative Care Essentials) of which two were optional and one was mandatory, and consisted of classroom sessions, webinars, and an in-person skills session. Evaluation of learners consisted of multiple choice questions and written assignments for each module. Evaluation of the course was based on semi-structured qualitative interviews conducted with both educator and learner, the latter of which will be published separately. Audio files were transcribed and underwent thematic analysis. For the discussion of the results, Khan's e-learning framework was used. RESULTS: Ten of the 12 participating educators were interviewed. Of the educators, three identified as mid-career and seven as senior faculty, ranging from six to 33 years of experience. Nine of ten reported an academic affiliation and all reported association with a teaching hospital. Themes identified from the educators' evaluations were: bridging the global gap, getting everybody on board, defining the educational scope, investing extensive hours of voluntary time and resources, benefiting within and beyond the curriculum, understanding the learner's experience, creating a community of shared learning, adapting future teaching and learning strategies, and envisioning long term sustainability. CONCLUSIONS: The first year of a novel, international, hybrid, and asynchronous neuropalliative care curriculum has been completed, and its educators have described both successes and avenues for improvement. Further research is planned to assess this curriculum from the learner perspective.


Assuntos
Currículo , Cuidados Paliativos , Pesquisa Qualitativa , Humanos , Instrução por Computador , Neurologia/educação , Educação a Distância
6.
Otolaryngol Head Neck Surg ; 170(6): 1696-1704, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38461407

RESUMO

OBJECTIVE: Mucosal decongestion with nasal sprays is a common treatment for nasal airway obstruction. However, the impact of mucosal decongestion on nasal aerodynamics and the physiological mechanism of nasal airflow sensation are incompletely understood. The objective of this study is to compare nasal airflow patterns in nasal airway obstruction (NAO) patients with and without mucosal decongestion and nondecongested healthy subjects. STUDY DESIGN: Cross-sectional study of a convenience sample. SETTING: Academic tertiary medical center. METHODS: Forty-five subjects were studied (15 nondecongested healthy subjects, 15 nondecongested NAO patients, and 15 decongested NAO patients). Three-dimensional models of the nasal anatomy were created from computed tomography scans. Steady-state simulations of airflow and heat transfer were conducted at 15 L/min inhalation rate using computational fluid dynamics. RESULTS: In the narrow side of the nose, unilateral nasal resistance was similar in decongested NAO patients and nondecongested healthy subjects, but substantially higher in nondecongested NAO patients. The vertical airflow distribution within the nasal cavity (inferior vs middle vs superior) was also similar in decongested NAO patients and nondecongested healthy subjects, but nondecongested NAO patients had substantially less middle airflow. Mucosal cooling, quantified by the surface area where heat flux exceeds 50 W/m2, was significantly higher in decongested NAO patients than in nondecongested NAO patients. CONCLUSION: This pilot study suggests that mucosal decongestion improves objective measures of nasal airflow, which is consistent with improved subjective sensation of nasal patency after decongestion.


Assuntos
Descongestionantes Nasais , Mucosa Nasal , Obstrução Nasal , Humanos , Projetos Piloto , Obstrução Nasal/fisiopatologia , Masculino , Feminino , Descongestionantes Nasais/administração & dosagem , Estudos Transversais , Adulto , Mucosa Nasal/fisiologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Sprays Nasais , Resistência das Vias Respiratórias/fisiologia
7.
Otolaryngol Head Neck Surg ; 170(6): 1581-1589, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38329226

RESUMO

OBJECTIVE: Endoscopy is routinely used to diagnose obstructive airway diseases. Currently, endoscopy is only a visualization technique and does not allow quantification of airspace cross-sectional areas (CSAs). This pilot study tested the hypothesis that CSAs can be accurately estimated from depth maps created from virtual endoscopy videos. STUDY DESIGN: Cross-sectional. SETTING: Academic tertiary medical center. METHODS: Virtual endoscopy and depth map videos of the nasal cavity were digitally created based on anatomically accurate three-dimensional (3D) models built from computed tomography scans of 30 subjects. A software tool was developed to outline the airway perimeter and estimate the airspace CSA from the depth maps. Two otolaryngologists used the software tool to estimate the nasopharynx CSA and the nasal valve minimal CSA (mCSA) in the left and right nasal cavities. Model validation statistics were performed. RESULTS: Nasopharynx CSA had a median percent error of 3.7% to 4.6% when compared to the true values measured in the 3D models. Nasal valve mCSA had a median percent error of 22.7% to 33.6% relative to the true values. Raters successfully used the software tool to identify subjects with nasal valve stenosis (ie, mCSA < 0.20 cm2) with a sensitivity of 83.3%, specificity ≥ 90.7%, and classification accuracy ≥ 90.0%. Interrater and intrarater agreements were high. CONCLUSION: This study demonstrates that airway CSAs in 3D models can be accurately estimated from depth maps. The development of artificial intelligence algorithms to compute depth maps may soon allow the quantification of airspace CSAs from clinical endoscopies.


Assuntos
Endoscopia , Imageamento Tridimensional , Cavidade Nasal , Estudo de Prova de Conceito , Humanos , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/anatomia & histologia , Projetos Piloto , Endoscopia/métodos , Masculino , Estudos Transversais , Feminino , Adulto , Tomografia Computadorizada por Raios X , Pessoa de Meia-Idade , Software , Nasofaringe/diagnóstico por imagem , Nasofaringe/anatomia & histologia
8.
Sci Rep ; 14(1): 1295, 2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-38221532

RESUMO

This study aims to identify healthcare costs indicators predicting secondary surgery for degenerative lumbar spine disease (DLSD), which significantly impacts healthcare budgets. Analyzing data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database of Republic of Korea (ROK), the study included 3881 patients who had surgery for lumbar disc herniation (LDH), lumbar spinal stenosis without spondylolisthesis (LSS without SPL), lumbar spinal stenosis with spondylolisthesis (LSS with SPL), and spondylolysis (SP) from 2006 to 2008. Patients were categorized into two groups: those undergoing secondary surgery (S-group) and those not (NS-group). Surgical and interim costs were compared, with S-group having higher secondary surgery costs ($1829.59 vs $1618.40 in NS-group, P = 0.002) and higher interim costs ($30.03; 1.86% of initial surgery costs vs $16.09; 0.99% of initial surgery costs in NS-group, P < 0.0001). The same trend was observed in LDH, LSS without SPL, and LSS with SPL (P < 0.0001). Monitoring interim costs trends post-initial surgery can effectively identify patients requiring secondary surgery.


Assuntos
Deslocamento do Disco Intervertebral , Estenose Espinal , Espondilolistese , Humanos , Estudos de Coortes , Estenose Espinal/cirurgia , Espondilolistese/cirurgia , Vértebras Lombares/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Resultado do Tratamento
9.
BMC Palliat Care ; 23(1): 17, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229044

RESUMO

BACKGROUND: Fewer than 1 in 20 people on the African continent in need of palliative care receive it. Malawi is a low-income country in sub-Saharan Africa that has yet to achieve advanced palliative care integration accompanied by unrestricted access to pain and symptom relieving palliative medicines. This paper studied the impact of Malawi's Waterloo Coalition Initiative (WCI) - a local project promoting palliative care integration through service development, staff training, and increased service access. METHODS: Interdisciplinary health professionals at 13 hospitals in southern Malawi were provided robust palliative care training over a 10-month period. We used a cross-sectional evaluation to measure palliative care integration based on 11 consensus-based indicators over a one-year period. RESULTS: 92% of hospitals made significant progress in all 11 indicators. Specifically, there was a 69% increase in the number of dedicated palliative care rooms/clinics, a total of 253 staff trained across all hospitals (a 220% increase in the region), substantive increases in the number of patients receiving or assessed for palliative care, and the number of hospitals that maintained access to morphine or other opioid analgesics while increasing the proportion of referrals to hospice or other palliative care programs. CONCLUSION: Palliative care is a component of universal health coverage and Sustainable Development Goal 3. The WCI has made tremendous strides in establishing and integrating palliative care services in Malawi with notable progress across 11 project indicators, demonstrating that increased palliative care access is possible in severely resource-constrained settings through sustained models of partnership at the local level.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Humanos , Malaui , Estudos Transversais , Dor
10.
Spine J ; 24(3): 417-423, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37844629

RESUMO

BACKGROUND CONTEXT: Multilevel cervical myelopathy is a common cause of spinal cord dysfunction in adults. Surgical intervention via laminoplasty can provide satisfactory clinical outcomes by expansive decompression of the spinal cord. Traditional suture or bone graft techniques have been associated with insufficient fixation, leading to premature closure and subsequent neurological deterioration. In contrast, plated laminoplasty has been shown to provide stable fixation to maintain canal enlargement, but longer-term outcomes are lacking. PURPOSE: To evaluate longer-term clinical outcomes and reoperations associated with plate-only open-door laminoplasty. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: Postoperative patients who underwent plate-only open door laminoplasty with minimum 5-year follow up. OUTCOME MEASURES: modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and 12-item Short Form Health Survey (SF-12). METHODS: All patients at a single academic institution who underwent plate-only open-door cervical laminoplasty from 9/1/2006 to 9/1/2016 were identified to ensure minimum 5 year follow up. Clinical outcomes included the modified Japanese Orthopaedic Association (mJOA) score, the Neck Disability Index (NDI), and the 12-item Short Form Health Survey (SF-12). The occurrence of any repeat operations on the cervical spine was evaluated, as well as its cause. The study team attempted to contact all eligible patients to achieve at least 5 years postoperative follow-up. Pairwise t tests were performed to compare clinical outcomes at preoperative, 6 months, 1-year, and final postoperative follow-up with an α level of 0.05. RESULTS: A total of 774 met the initial inclusion criteria, of which 157 were included in the study (20.3%). Most common reasons for exclusion included inability to reach after 3 attempts (49.48%), inactive phone numbers (20.28%), and patient declining (3.49%). Included patients had an average age of 60.66±10.63 and an average follow-up time of 8.37±2.57 years (minimum 5 years). mJOA scores (preoperative 11.59±2.16) improved significantly at 6-months (14.57±2.07, p<.001), 1-year (15.19±1.95, p<.001), and final follow-up (14.59±2.63, p<.001). NDI (preoperative 33.89±18.54) improved significantly at 6 months (27.89±19.72, p=.03), 1-year (25.96±19.79, p=.01) and final follow-up (17.88±17.17, p<.001). SF-12 MCS (preoperative 44.73) improved significantly at 6 months (52.01, p=.001), 1-year (51.62, p=.008), and final follow-up (52.32, p<.001). No patient underwent reoperations for plate failure or canal closure with recurrent stenosis. Reoperations for progressive spondylosis during the follow up period were rare and occurred in only three patients for new onset radiculopathy (1.9%) and two patients for myelopathy (1.3%) at an average of 3.2 years postoperative. There were no reoperations performed for adjacent segment disease. CONCLUSIONS: At a minimum of 5 years and an average of more than 8 years postoperative, laminoplasty was associated with significant and sustained improvements in mJOA, NDI, and SF-12 MCS. Importantly, no patients underwent revision surgery for plate failure or recurrent canal closure. Reoperations for new onset radiculopathy and myelopathy were also very rare over the 8-year average follow-up period, with no reoperations for adjacent segment disease. Plate-only laminoplasty is a durable means of treating multilevel myelopathy with excellent longer-term outcomes and a very low risk of reoperation, either for premature closure or the inevitable spondylotic changes that occur over time in patients with similar baseline characteristics to the study population.


Assuntos
Laminoplastia , Radiculopatia , Doenças da Medula Espinal , Espondilose , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Seguimentos , Reoperação/efeitos adversos , Resultado do Tratamento , Laminoplastia/efeitos adversos , Laminoplastia/métodos , Radiculopatia/cirurgia , Doenças da Medula Espinal/cirurgia , Vértebras Cervicais/cirurgia , Laminectomia/efeitos adversos , Espondilose/complicações , Estudos Retrospectivos
11.
BMJ Open ; 13(9): e069410, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37678946

RESUMO

INTRODUCTION: Caregivers of patients with primary malignant brain tumours experience substantial psychological distress while caring for someone with a progressive, life-limiting neurological illness. However, there are few interventions aimed at addressing the psychosocial needs of this population. We developed and are testing a population-specific, evidence-based, telehealth intervention (NeuroCARE) to reduce anxiety symptoms and improve psychosocial functioning in this caregiver population. METHODS AND ANALYSIS: This study is a non-blinded, randomised controlled trial of a psychological intervention for caregivers of patients with primary malignant brain tumours receiving care at the Massachusetts General Hospital Cancer Center or Dana-Farber Cancer Institute. We will enrol 120 caregivers who screen positive for heightened anxiety. Participants will be randomised 1:1 to the NeuroCARE intervention or a usual care control condition. Caregivers assigned to NeuroCARE will complete six individual telehealth sessions with a trained behavioural health specialist over 12 weeks. Caregivers randomised to the control condition will receive usual care, including possible referral to social work or other appropriate resources. Participants will complete self-report questionnaires at baseline and 11 weeks and 16 weeks postrandomisation. The primary outcome is anxiety symptoms at 11 weeks among NeuroCARE participants, compared with usual care. Secondary outcomes include caregiver-reported depressive symptoms, quality of life, caregiver burden, caregiving self-efficacy, perceived coping skills and post-traumatic stress disorder symptoms. We also will explore potential mediators of the NeuroCARE effect on caregiver anxiety symptoms. ETHICS AND DISSEMINATION: The study is funded by a Career Development Award from Conquer Cancer, the American Society of Clinical Oncology Foundation (award number 2019CDA-7743456038) and approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (Protocol #19-250 V.10.1). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. Results will be presented at scientific meetings and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04109209.


Assuntos
Neoplasias Encefálicas , Cuidadores , Humanos , Intervenção Psicossocial , Qualidade de Vida , Sobrecarga do Cuidador , Neoplasias Encefálicas/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Curr Neurol Neurosci Rep ; 23(11): 645-656, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37751050

RESUMO

PURPOSE OF REVIEW: While the benefits of palliative care for patients with cancer are well established, palliative care in neuro-oncology is still in its early stages. However, in recent years, there has been increasing attention drawn to the need for better palliative care for patients with brain tumors. RECENT FINDINGS: There is a growing body of literature demonstrating the high symptom burden and significant supportive care and information needs of these patients and their caregivers. In the area of caregiver needs, the last 3 years has seen a more rapid growth in recognizing and characterizing these needs. However, there remains a knowledge gap regarding the optimal means of addressing these needs. In this article, we outline important recent advances in the literature on palliative care for patients with brain tumors and highlight areas in need of greater attention and investigation.


Assuntos
Neoplasias Encefálicas , Cuidados Paliativos , Humanos , Qualidade de Vida , Neoplasias Encefálicas/terapia , Cuidadores
14.
Antibodies (Basel) ; 12(3)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37606434

RESUMO

Paraneoplastic antibody syndromes result from the anti-tumor antibody response against normal antigens ectopically expressed by tumor cells. Although this antibody response plays an important role in helping clear a nascent or established tumor, the engagement of antigens expressed in healthy tissues can lead to complex clinical syndromes with challenging diagnosis and management. The majority of known paraneoplastic antibody syndromes have been found to affect the central and peripheral nervous system. The present review provides an update on the pathophysiology of paraneoplastic neurologic syndromes, as well as recommendations for their diagnosis and treatment.

15.
Oncologist ; 28(11): 1007-e1107, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37555284

RESUMO

BACKGROUND: CREBBP and EP300 mutations occur at a frequency of 15% and 13%, respectively, in small cell lung cancer (SCLC), and preclinical models demonstrated susceptibility to targeting with HDAC inhibitors. METHODS: Patients with treatment-naïve extensive-stage SCLC, ECOG ≤2 were enrolled and treated with entinostat orally weekly (4 dose levels, DL) in combination with standard dose carboplatin, etoposide, and atezolizumab. Cohort allocation was determined by Bayesian optimal interval (BOIN) design targeting an MTD with a DLT rate of 20%. RESULTS: Three patients were enrolled and treated at DL1 with entinostat 2 mg. Patients were aged 69-83; 2 male, 1 female; 2 were ECOG 1, and 1 was ECOG 0. The most common adverse events (AEs) were anemia (3), neutropenia (3), thrombocytopenia (2), leukopenia (2), and hypocalcemia (2). Two experienced DLTs during cycle 1: (1) grade (Gr) 4 febrile neutropenia, and (1) Gr 5 sepsis. BOIN design required stopping accrual to DL1, and the trial was closed to further accrual. Entinostat and atezolizumab pharmacokinetics were both comparable to historical controls. CONCLUSION: Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029).


Assuntos
Anemia , Neoplasias Pulmonares , Neutropenia , Carcinoma de Pequenas Células do Pulmão , Trombocitopenia , Humanos , Masculino , Feminino , Etoposídeo , Carboplatina , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Teorema de Bayes , Neutropenia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
16.
Clin J Gastroenterol ; 16(5): 680-684, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37452993

RESUMO

Immune checkpoint inhibitors (ICI) have transformed the management of cancer, producing durable responses in a subset of treated patients across multiple malignancies. Immune-mediated diarrhea and colitis (imDC) occurs in up to 20% of ICI-treated patients. The risk of ICI imDC is dependent upon the agent and is commoner with anti-CTLA-4 compared to anti-PD-1 ICIs. Generally, imDC is treated with steroids and agents targeting TNFα or α4ß7 integrin. However, the management of steroids and/or biologic refractory imDC is unclear. We present a case of imDC in a 68-year-old female who failed to respond clinically, biochemically and immunohistochemically to corticosteroids, infliximab and vedolizumab. A trial of tofacitinib, a pan-JAK inhibitor, led to rapid clinical, biochemical and immunohistochemical control of imDC. ICIs result in a striking accumulation of cytotoxic and proliferative CD8 + T cells within tumor. However, the cellular and molecular mechanisms underlying imDC remain unclear. Herein, we observed significant T cell enrichment; and the successful treatment with tofacitinib highlights the potential of multiple convergent inflammatory pathways in imDC and inflammatory colitis.

18.
Ann Surg Oncol ; 30(12): 7517-7526, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37314541

RESUMO

BACKGROUND: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients. METHODS: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS). RESULTS: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006). CONCLUSIONS: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/genética , Pseudomixoma Peritoneal/terapia , Pseudomixoma Peritoneal/metabolismo , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/terapia , Neoplasias do Apêndice/genética , Neoplasias do Apêndice/terapia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Serina-Treonina Quinases TOR/genética , Procedimentos Cirúrgicos de Citorredução
19.
Sci Rep ; 13(1): 6317, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072455

RESUMO

Surgical outcomes of degenerative cervical spinal disease are dependent on the selection of surgical techniques. Although a standardized decision cannot be made in an actual clinical setting, continued education is provided to standardize the medical practice among surgeons. Therefore, it is necessary to supervise and regularly update overall surgical outcomes. This study aimed to compare the rate of additional surgery between anterior and posterior surgeries for degenerative cervical spinal disease using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) nationwide patient database. The NHIS-NSC is a population-based cohort with about a million participants. This retrospective cohort study included 741 adult patients (> 18 years) who underwent their first cervical spinal surgery for degenerative cervical spinal disease. The median follow-up period was 7.3 years. An event was defined as the registration of any type of cervical spinal surgery during the follow-up period. Event-free survival analysis was used for outcome analysis, and the following factors were used as covariates for adjustment: location of disease, sex, age, type of insurance, disability, type of hospital, Charles comorbidity Index, and osteoporosis. Anterior cervical surgery was selected for 75.0% of the patients, and posterior cervical surgery for the remaining 25.0%. Cervical radiculopathy due to foraminal stenosis, hard disc, or soft disc was the primary diagnosis in 78.0% of the patients, and central spinal stenosis was the primary diagnosis in 22.0% of them. Additional surgery was performed for 5.0% of the patients after anterior cervical surgery and 6.5% of the patients after posterior cervical surgery (adjusted subhazard ratio, 0.83; 95% confidence interval, 0.40-1.74). The rates of additional surgery were not different between anterior and posterior cervical surgeries. The results would be helpful in evaluating current practice as a whole and adjusting the health insurance policy.


Assuntos
Radiculopatia , Doenças da Coluna Vertebral , Fusão Vertebral , Adulto , Humanos , Estudos Retrospectivos , Discotomia/métodos , Fusão Vertebral/métodos , Vértebras Cervicais/cirurgia , Radiculopatia/cirurgia , Doenças da Coluna Vertebral/cirurgia , Resultado do Tratamento
20.
Clin Spine Surg ; 36(3): 96-105, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36959181

RESUMO

STUDY DESIGN/SETTING: Retrospective review of a national multi-institutional database of 27,808 extradural cervical spine procedures performed between January 2017 and May 2021. OBJECTIVE: Characterize intraoperative neuromonitoring alerts by the patterns of modalities and nerves/muscles involved and quantify risk of new-onset neurological deficit for patients with a primary diagnosis of myelopathy, stenosis, or radiculopathy. SUMMARY OF BACKGROUND DATA: Phenotyping alert patterns and linking those patterns with risk is needed to facilitate clinical decision-making. METHODS: Cases with alerts were categorized by patterns of modalities or nerves/muscles involved, and alert status at closure. Unadjusted odds ratios (ORs) for new-onset neurological deficit were calculated. A mixed-effects logistic regression model controlling for demographic and operative factors, with random intercepts to account for clustering in outcomes by surgeon and surgical neurophysiologist was also used to calculate ORs and probabilities of neurological deficit. RESULTS: There was significantly increased risk of a new neurological deficit for procedures involving posterior compared with anterior approaches (OR: 1.82, P=0.001) and procedures involving three levels compared with one (OR: 2.17, P=0.001). Odds of a deficit were lower for patients with radiculopathy compared with myelopathy (OR: 0.69, P=0.058). Compared with cases with no alerts, those with unresolved Spinal Cord alerts were associated with the greatest elevation in risk (OR: 289.05) followed by unresolved C5-6 Nerve Root (OR: 172.7), C5-T1 Nerve Root/Arm (OR: 162.89), C7 Nerve Root (OR:84.2), and C8-T1 Nerve Root alerts (OR:75.49, all P<0.001). Significant reductions in risk were seen for resolved Spinal Cord, C5-6 Nerve Root, and C8-T1 nerve alerts. Overall, unresolved motor evoked potential and somatosensory evoked potential alerts were associated with the greatest elevation in risk (OR:340.92) followed by unresolved motor evoked potential-only (OR:140.6) and unresolved somatosensory evoked potential-Only alerts (OR:78.3, all P<0.001). These relationships were similar across diagnostic cohorts. CONCLUSIONS: Risk elevation and risk mitigation after an intraoperative neuromonitoring alert during surgery is dependent on the type and pattern of alert.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Radiculopatia , Doenças da Medula Espinal , Humanos , Radiculopatia/cirurgia , Radiculopatia/etiologia , Vértebras Cervicais/cirurgia , Procedimentos Neurocirúrgicos/métodos , Potencial Evocado Motor/fisiologia , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/etiologia , Estudos Retrospectivos , Monitorização Neurofisiológica Intraoperatória/métodos
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