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1.
BMC Med Educ ; 24(1): 185, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395858

RESUMEN

BACKGROUND: The increasing linguistic and cultural diversity in the United States underscores the necessity of enhancing healthcare professionals' cross-cultural communication skills. This study focuses on incorporating interpreter and limited-English proficiency (LEP) patient training into the medical and physician assistant student curriculum. This aims to improve equitable care provision, addressing the vulnerability of LEP patients to healthcare disparities, including errors and reduced access. Though training is recognized as crucial, opportunities in medical curricula remain limited. METHODS: To bridge this gap, a novel initiative was introduced in a medical school, involving second-year students in clinical sessions with actual LEP patients and interpreters. These sessions featured interpreter input, patient interactions, and feedback from interpreters and clinical preceptors. A survey assessed the perspectives of students, preceptors, and interpreters. RESULTS: Outcomes revealed positive reception of interpreter and LEP patient integration. Students gained confidence in working with interpreters and valued interpreter feedback. Preceptors recognized the sessions' value in preparing students for future clinical interactions. CONCLUSIONS: This study underscores the importance of involving experienced interpreters in training students for real-world interactions with LEP patients. Early interpreter training enhances students' communication skills and ability to serve linguistically diverse populations. Further exploration could expand languages and interpretation modes and assess long-term effects on students' clinical performance. By effectively training future healthcare professionals to navigate language barriers and cultural diversity, this research contributes to equitable patient care in diverse communities.


Asunto(s)
Asistentes Médicos , Estudiantes de Medicina , Humanos , Estados Unidos , Comparación Transcultural , Traducción , Comunicación , Barreras de Comunicación , Relaciones Médico-Paciente
2.
J Gen Intern Med ; 34(4): 634-635, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30756301

RESUMEN

The Centers for Medicare and Medicaid Services (CMS) recently revised their Medicare Claims Processing Manual with the addition of CR 10412, a provision that permits teaching providers to fully bill for medical student notes. This change will have significant implications on the documentation duties of teaching physicians and trainees. Potential benefits of this provision include reduced documentation burden on house officers, improved medical student empowerment, and the infusion of more original content into the electronic medical record. However, these benefits may be offset by shifting the burden of documentation onto medical students, which may compromise their time spent with patients and overall wellness. In this perspective, we review the changes that occurred with CR 10412 and their potential impact on documentation across the medical education spectrum.


Asunto(s)
Registros Electrónicos de Salud/legislación & jurisprudencia , Medicare/legislación & jurisprudencia , Estudiantes de Medicina , Centers for Medicare and Medicaid Services, U.S. , Documentación , Humanos , Medicare/economía , Mecanismo de Reembolso/organización & administración , Estados Unidos
3.
J Gen Intern Med ; 32(2): 182-188, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27896691

RESUMEN

BACKGROUND: Patient history-taking is an essential clinical skill, with effects on diagnostic reasoning, patient-physician relationships, and more. We evaluated the impact of using a structured, timeline-based format, the Chronology of Present Illness (CPI), to guide the initial patient interaction. OBJECTIVE: To determine the feasibility and impact of the CPI on the patient interview, written notes, and communication with other providers. DESIGN: Internal medicine residents used the CPI during a 2-week night-float rotation. For the first week, residents interviewed, documented, and presented patient histories according to their normal practices. They then attended a brief educational session describing the CPI, and were asked to use this method for new patient interviews, notes, and handoffs during the second week. Night and day teams evaluated the method using retrospective pre-post comparisons. PARTICIPANTS: Twenty-two internal medicine residents in their second or third postgraduate year. INTERVENTION: An educational dinner describing the format and potential benefits of using the CPI. MAIN MEASURES: Retrospective pre-post surveys on the efficiency, quality, and clarity of the patient interaction, written note, and verbal handoff, as well as open-ended comments. Respondents included night-float residents, day team residents, and attending physicians. KEY RESULTS: All night-float residents responded, reporting significant improvements in written note, verbal sign-out, assessment and plan, patient interaction, and overall efficiency (p < 0.05). Day team residents (n = 76) also reported increased clarity in verbal sign-out and written note, improved efficiency, and improved preparedness for presenting the patient (p < 0.05). Attending physician ratings did not differ between groups. CONCLUSIONS: Resident ratings indicate that the CPI can improve key aspects of patient care, including the patient interview, note, and physician-physician communication. These results suggest that the method should be taught and implemented more frequently.


Asunto(s)
Continuidad de la Atención al Paciente/normas , Medicina Interna/educación , Anamnesis/métodos , Relaciones Médico-Paciente , Calidad de la Atención de Salud , Estudios de Factibilidad , Humanos , Internado y Residencia , Proyectos Piloto , Encuestas y Cuestionarios
5.
BMC Med Educ ; 16: 139, 2016 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-27160008

RESUMEN

BACKGROUND: Internal Medicine residents experience conflict between inpatient and outpatient medicine responsibilities. Outpatient "between visit" responsibilities such as reviewing lab and imaging data, responding to medication refill requests and replying to patient inquiries compete for time and attention with inpatient duties. By examining Electronic Health Record (EHR) audits, our study quantitatively describes this balance between competing responsibilities, focusing on housestaff participation with "between visit" outpatient responsibilities. METHODS: We examined EHR log-in data from 2012-2013 for 41 residents (R1 to R3) assigned to a large academic center's continuity clinic. From the EHR log-in data, we examined housestaff compliance with "between visit" tasks, based on official clinic standards. We used generalized estimating equations to evaluate housestaff compliance with between visit tasks and amount of time spent on tasks. We examined the relationship between compliance with between visit tasks and resident year of training, rotation type (elective or required) and interest in primary care. RESULTS: Housestaff compliance with logging in to complete "between visit" tasks varied significantly depending on rotation, with overall compliance of 45% during core inpatient rotations compared to 68% during electives (p = 0.01). Compliance did not significantly vary by interest in primary care or training level. Once logged in, housestaff spent a mean 53 min per week logged in while on electives, compared to 55 min on required rotations (p = 0.90). CONCLUSIONS: Our study quantitatively highlights the difficulty of attending to outpatient responsibilities during busy core inpatient rotations, which comprise the bulk of residency at our institution and at others. Our results reinforce the need to continue development and study of innovative systems for coverage of "between visit" responsibilities, including shared coverage models among multiple residents and shared coverage models between residents and clinic attendings, both of which require a balance between clinic efficiency and resident ownership, autonomy and learning.


Asunto(s)
Atención Ambulatoria , Medicina Interna/educación , Internado y Residencia , Rol del Médico , Adhesión a Directriz , Humanos , Factores de Tiempo , Carga de Trabajo
6.
Jt Comm J Qual Patient Saf ; 40(2): 77-82, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24716330

RESUMEN

As complexity of care of hospitalized patients has increased, the need for communication and collaboration among members of the team caring for the patient has become increasingly important. This often takes the form of a nurse's need to contact a patient's physician to discuss some aspect of care and modify treatment plans. Errors in communication delay care and can pose risk to patients. This report describes the successful implementation of a standardized team-based paging system at an academic center. Results showed a substantial improvement in nurses' perceptions of knowing how to contact the correct physician when discussion of the patient's care is needed. This improvement was found across multiple medical and surgical specialties and was particularly effective for services with the greatest communication problems.


Asunto(s)
Centros Médicos Académicos/organización & administración , Comunicación , Grupo de Atención al Paciente/organización & administración , Mejoramiento de la Calidad/organización & administración , Enfermeras y Enfermeros , Médicos , Factores de Tiempo
8.
Leuk Lymphoma ; 64(1): 42-56, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36270021

RESUMEN

Chronic lymphocytic leukemia (CLL) is a disorder of mature malignant B cells with multiple elements of immune dysfunction. Infections are common in CLL patients due to complex immunodeficiency. Vaccines are used as preventative measures for common diseases including influenza, pneumococcus, tetanus/diphtheria and shingles in the general population. Vaccines are utilized to mitigate this risk, although there have been some concerns regarding the efficacy of vaccines in the CLL population due to the inherent complex immune dysfunction associated with the disease. In this review, we describe the clinical and laboratory indicators for efficacy of the vaccines in the CLL population (including COVID-19, influenza, pneumonia, herpes zoster, and tetanus) and discuss immunization recommendations for patients with CLL.


Asunto(s)
COVID-19 , Herpes Zóster , Gripe Humana , Leucemia Linfocítica Crónica de Células B , Tétanos , Vacunas , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/terapia , Tétanos/complicaciones , Tétanos/prevención & control , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación , Herpes Zóster/prevención & control
9.
Exp Biol Med (Maywood) ; 247(4): 330-337, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35068219

RESUMEN

Cytokine storm is an umbrella term that describes an inflammatory syndrome characterized by elevated levels of circulating cytokines and hyperactivation of innate and/or adaptive immune cells. One type of cytokine storm is hemophagocytic lymphohistiocytosis (HLH), which can be either primary or secondary. Severe COVID-19-associated pneumonia and acute respiratory distress syndrome (ARDS) can also lead to cytokine storm/cytokine release syndrome (CS/CRS) and, more rarely, meet criteria for the diagnosis of secondary HLH. Here, we review the immunobiology of primary and secondary HLH and examine whether COVID-19-associated CS/CRS can be discriminated from non-COVID-19 secondary HLH. Finally, we review differences in immunobiology between these different entities, which may inform both clinical diagnosis and treatment of patients.


Asunto(s)
COVID-19/complicaciones , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/terapia , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/etiología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Síndrome de Liberación de Citoquinas/virología , Humanos , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/terapia
10.
Exp Biol Med (Maywood) ; 246(1): 5-9, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32972235

RESUMEN

IMPACT STATEMENT: Severe COVID-19 associated pneumonia and acute respiratory distress syndrome has recently been described with life-threatening features of cytokine storm and loosely referred to as hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS). Although a recent report indicated favorable responses to the interleukin-1 receptor antagonist, anakinra in eight patients with COVID-19 secondary HLH diagnosed using the HScore calculation, others have suggested that the diagnosis of secondary HLH is uncommon and that the use of the HScore has limited value in guiding immunomodulatory therapy for COVID-19. Here, we provide additional perspective on this important controversy based upon comparisons between 14 COVID-19 cytokine storm patients and 10 secondary HLH patients seen immediately prior to the pandemic. We hypothesize that identification of HLH may relate to the severity or timing of cytokine release and suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria.


Asunto(s)
COVID-19/complicaciones , Síndrome de Liberación de Citoquinas/etiología , Linfohistiocitosis Hemofagocítica/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfohistiocitosis Hemofagocítica/virología , Masculino , Persona de Mediana Edad , Esplenomegalia/etiología
11.
BMJ Case Rep ; 14(6)2021 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-34127502

RESUMEN

Struma ovarii (SO) is a rare ovarian teratoma containing abundant mature thyroid tissue. Malignant transformation is even less common and distant metastasis is documented in about 5%-10%. The time from diagnosis of primary SO to metastatic disease varies. As malignant SO is rare, there are no uniform diagnostic criteria or treatment guidelines. Management is usually extrapolated from that of thyroid malignancy. We report a patient who relapsed 12 years from the initial diagnosis and metastasised to the lungs 5 years after the first recurrence. Our patient was treated with total thyroidectomy followed by radioactive iodine, and retreated on progression in the lungs. The tumour harboured high microsatellite instability and treatment with programmed cell death protein 1 inhibitor was initiated. This case shows the long latency of SO with the rare phenomenon of metastasis. It also highlights the importance of molecular testing for rare cancers such as this.


Asunto(s)
Neoplasias Ováricas , Estruma Ovárico , Neoplasias de la Tiroides , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Inestabilidad de Microsatélites , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Estruma Ovárico/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia
12.
Therap Adv Gastroenterol ; 14: 17562848211014818, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34025781

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) accounts for about 3% of all cancers in the United States and about 7% of all cancer deaths. Despite the lower prevalence relative to other solid tumors, it is one of the leading causes of cancer-related death in the US. PDAC is highly resistant to chemotherapy as well as radiation therapy. Current standard-of-care chemotherapeutic regimens provide transient disease control but eventually tumors develop chemoresistance. Tumors that are deficient in DNA damage repair mechanisms such as BRCA mutants respond better to platinum-based chemotherapies. However, these tumor cells can utilize the poly adenosine diphosphate (ADP)-ribose polymerase (PARP) as a salvage DNA repair pathway to prolong survival. Hence, in the presence of BRCA mutations, the inhibition of the PARP pathway can lead to tumor cell death. This provides the rationale for using PARP inhibitors in patients with BRCA mutated PDAC. The phase III POLO trial showed a near doubling of progression-free survival (PFS) compared with placebo in advanced PDAC when a PARP inhibitor, olaparib, was used as maintenance therapy. As a result, the US Food and Drug Administration (FDA) approved olaparib as a maintenance treatment for germline BRCA mutated advanced PDAC that has not progressed on platinum-based chemotherapy. The success of olaparib in treating advanced PDAC opened the new field for utilizing PARP inhibitors in patients with DNA damage repair (DDR) gene defects. Currently, many clinical trials with various PARP inhibitors are ongoing either as monotherapy or in combination with other agents. In addition to germline/somatic BRCA mutations, some trials are enrolling patients with defects in other DDR genes such as ATM, PALB2, and CHEK2. With many ongoing PARP inhibitor trials, it is hopeful that the management of PDAC will continuously evolve and eventually lead to improved patient outcomes.

13.
Cancer Med J ; 4(Suppl 3): 1-6, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33655238

RESUMEN

BACKGROUND: Pegfilgrastim is administered 24 hours. after chemotherapy to reduce risks of myelosuppression. This requires an additional clinic visit, which can be difficult for some patients (pts) due to work and transportation issues. In GI malignancies, patients receiving capecitabine-based regimens also require pegfilgrastim to reduce myelotoxicity. We present here the first study to analyze safety and efficacy of administering pegfilgrastim on the same day as capecitabine-based regimens in patients with GI malignancies. METHODS: We evaluated 157 patients with GI malignancies who received a capecitabine-based chemotherapy regimen, including XELOX, EOX, ECX, XELIRI, MIXE, gemcitabine-capecitabine and same-day pegfilgrastim (6 mg) within 1 hr of completion of systemic agents. As per institutional guidelines, patients were counseled on risks of same-day pegfilgrastim prior to its administration. Patients were followed to determine the degree of neutropenia and toxicity. RESULTS: A total of 914 chemotherapy cycles in 157 patients were analyzed. Median ANC nadir for all cycles was 5634/uL (range: 450 - 23800). Grade 1 and 2 neutropenia developed in 11 of 914 cycles. Bone pain reported in 9 pts. There was 1 episode of grade >3 neutropenia resulting in infection and antibiotic use. No other patient required dose reductions, chemotherapy delays, or hospitalizations. No increased toxicity of capecitabine was noticed. CONCLUSIONS: We believe our study is the first in GI malignancies to report that same-day pegfilgrastim administration with capecitabine-based regimens may be as effective and safe as next-day administration. Additionally, given the absence of CD in human bone marrow, it appears capecitabine can be used concurrently with pegfilgrastim. Prospective studies should be done to further investigate, as this practice can benefit patients clinically, decrease office visits, increase patient's satisfaction and reduce healthcare costs.

14.
Case Rep Oncol Med ; 2020: 6154213, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32110454

RESUMEN

Combination therapy with ibrutinib and cetuximab is being studied in a phase 1b/2 trial in patients with advanced gastrointestinal and genitourinary malignancies. Rash is a common cutaneous adverse effect for both medications. Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment of several hematologic malignancies. The rash can be asymptomatic, nonpalpable, mild skin eruption, or palpable purpuric rash. A rarer panniculitis form has also been reported. Cetuximab, an epidermal growth factor (EGFR) inhibitor, approved for treatment in head and neck and advanced gastrointestinal malignancies is also known to cause acneiform rash in majority of patients. The rash is due to inhibition of EGFR in the basal keratinocytes and hair follicles. In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash. The combination therapy with the BTK inhibitor and a direct EGFR inhibitor may potentiate the rash inducing effects of the drugs. Here, we describe a case of vasculitis in a patient with metastatic colon cancer who received both ibrutinib and cetuximab on a phase Ib/II clinical trial.

15.
Cureus ; 12(8): e9537, 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32905172

RESUMEN

Background Capstone, or bootcamp, courses have been shown to increase the knowledge, skills, and self-efficacy of students prior to starting intern year and have been recommended by the Alliance for Clinical Education (ACE) to be incorporated into the fourth-year medical school curricula. However, a paucity of research exists regarding the exploration of the student perspective on critical curricular content and teaching strategies in a capstone course. Self-efficacy, one's subjective task-specific judgment of capability, has served in the literature as a framework for capstone outcomes and is derived from four sources of experiences: practice, observation of others, feedback, and one's emotional reaction to difficult situations. Utilizing this framework, we aimed to evaluate the impact of our capstone curriculum on students' self-efficacy and to identify critical curricular content and teaching strategies that affected students' self-efficacy and their transition into residency. Methods We designed a mixed methods study of our institution's capstone course in May 2019. Students were invited to participate in the retrospective pre- and post- self-efficacy survey and focus group immediately after the capstone and in semi-structured interviews four months after they began the intern year. Themes were identified via qualitative analysis using inductive coding to allow participants' voices to guide code development and deductive analysis using codes derived from the self-efficacy framework. Results  Nine enrolled students participated in the study (surveys n=8, focus group n=7, follow-up interview n=6). Students reported the capstone was a very valuable educational experience (median 4.5 [interquartile range, or IQR 4-5]), increased their preparedness for intern year (median 5 [IQR 4.25-5]) and increased self-efficacy in multiple domains. Qualitative analysis revealed the critical curricular elements that most impacted students' self-efficacy were practical and communication skills to which students previously had limited exposure, in particular managing acute clinical needs, overnight cross-cover pages, inpatient pharmacology, daily intern communication (handoffs, consults, consenting), and end-of-life communication (goals of care, code status, pronouncing death). While all four sources contributed to self-efficacy, students reported that instructor and peer feedback were fundamental to providing context and substance to their performance. Students preferred practice-based learning via high-fidelity simulation and small groups for familiar tasks (daily intern communication, overnight pages, pharmacology) and observation of peers for new tasks (end-of-life communication and acute clinical deterioration). Conclusions This is the first study describing students' perspectives on critical curricular content and teaching strategies for a capstone course derived from qualitative analysis. Practical and communication skills with previously limited clerkship exposure and task-specific learning strategies increased the students' self-efficacy. Constructive feedback provided an important source of self-efficacy for all tasks, augmenting the benefits of practice and observation. This data provides preliminary groundwork for future research as multi-institutional studies are necessary to better understand students' needs around the curriculum to address residency transition.

16.
Therap Adv Gastroenterol ; 13: 1756284820974912, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33281939

RESUMEN

BACKGROUND: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. METHODS: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan-Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. RESULTS: A total of 73 patients (median age: 73 years; range: 66-93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. CONCLUSION: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.

17.
J Cell Signal ; 1(2): 23-30, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32607505

RESUMEN

INTRODUCTION: While the global COVID-19 pandemic has challenged the entire humanity and health systems, it also triggered researchers to urgently perform clinical trials to assess the safety and efficacy of many agents and modalities to combat COVID-19. As of April 22, over 650 clinical studies have been registered both in USA and internationally. Results from these studies are also coming at a brisk pace in this unprecedented emergency. AREAS COVERED: We searched the NCI website and Medline and summarize various national and international clinical trials and summarize few of the pivotal ones in this paper, including those specific to oncology population. Two hundred and eighty four studies are actively recruiting adults and children with confirmed COVID-19, including 25 are early-phase I/phase I, 72 phase II, 58 phase III, 12 phase IV, and 31 other trials. They can be categorized into four groups: drugs that combat SARS-CoV-2, immunomodulatory agents to counteract cytokine storm, convalescence plasma therapies and vaccines trials. EXPERT OPINION: It is hoped that these efforts will results in a successful treatment to COVID-19, especially in a timely fashion before the second pandemic expected in fall. It is essential to acknowledge the devotion and hard work of the clinical research team and clinical research volunteers.

18.
Future Sci OA ; 6(9): FSO606, 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-33235805

RESUMEN

AIM: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. METHODS: Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. RESULTS: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA-ISH and p16 IHC is fair (Gwet's AC1 = 0.318). CONCLUSION: The agreement between p16 IHC and HPV-DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC.

20.
Exp Hematol ; 36(7): 832-44, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18400360

RESUMEN

OBJECTIVE: The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex network of intracellular signaling pathways. In this study, we have investigated the role of two members of the calcium/calmodulin-dependent protein kinase (CaMK) signaling cascade, CaMK I-like kinase (CKLiK) and CaMKKalpha, in regulating neutrophil differentiation and functional activation. MATERIALS AND METHODS: Mouse myeloid cell lines were used to examine the expression of a CaMK cascade in developing neutrophils and to examine the effects of constitutive activation vs inhibition of CaMKs on neutrophil maturation. RESULTS: Expression of CaMKKalpha was shown to increase during neutrophil differentiation in multiple cell lines, whereas expression of CKLiK increased as multipotent progenitors committed to promyelocytes, but then decreased as cells differentiated into mature neutrophils. Expression of constitutively active CKLiKs did not affect morphologic maturation, but caused dramatic decreases in both respiratory burst responses and chemotaxis. This loss of neutrophil function was accompanied by reduced secondary granule and gp91(phox) gene expression. The CaMK inhibitor KN-93 attenuated cytokine-stimulated proliferative responses in promyelocytic cell lines, and inhibited the respiratory burst. Similar data were observed with the CaMKKalpha inhibitor, STO-609. CONCLUSIONS: Overactivation of a cascade of CaMKs inhibits neutrophil maturation, suggesting that these kinases play an antagonistic role during neutrophil differentiation, but at least one CaMK is required for myeloid cell expansion and functional activation.


Asunto(s)
Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/biosíntesis , Proteína Quinasa Tipo 1 Dependiente de Calcio Calmodulina/biosíntesis , Diferenciación Celular/fisiología , Regulación Enzimológica de la Expresión Génica/fisiología , Activación Neutrófila/fisiología , Neutrófilos/enzimología , Animales , Bencimidazoles/farmacología , Bencilaminas/farmacología , Células COS , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/antagonistas & inhibidores , Proteína Quinasa Tipo 1 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Chlorocebus aethiops , Citocinas/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Células HL-60 , Humanos , Inmunidad Innata/fisiología , Glicoproteínas de Membrana/biosíntesis , Ratones , NADPH Oxidasa 2 , NADPH Oxidasas/biosíntesis , Naftalimidas/farmacología , Activación Neutrófila/efectos de los fármacos , Neutrófilos/citología , Inhibidores de Proteínas Quinasas/farmacología , Estallido Respiratorio/efectos de los fármacos , Estallido Respiratorio/fisiología , Vesículas Secretoras/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Sulfonamidas/farmacología
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