Low Rates of Colorectal Cancer Screening in First-Degree Relatives of Our Patients: Are We Failing Them?

BACKGROUND: Guidelines recommend screening those with a family history of early-onset colorectal cancer at age 40 years or 10 years before the age of their relative's diagnosis. Currently, there is no literature reporting the screening rate in these individuals, and no protocols are in place to identify and target this population for screening awareness. OBJECTIVE: This study aimed to assess adherence to current screening guidelines among first-degree relatives of patients with early-onset colorectal cancer. DESIGN: Retrospective and qualitative study involving a telephone survey where patients were asked about relative's screening status and barriers to screening. SETTINGS: Two community-based institutions between January 2018 and December 2021. PATIENTS: Individuals diagnosed with early-onset colorectal cancer who had undergone surgery at our institutions. MAIN OUTCOME MEASURES: Rate of screening in first-degree relatives of our patients with early-onset colorectal cancer. Other factors measured included demographics, clinicopathologic characteristics, and screening barriers. RESULTS: Thirty-six patients were identified. The survey response rate was 66.6% (n = 24). A total of 88 first-degree relatives who met the screening criteria resulted in 67.1% of patients (n = 59) having a known screening status. Of the 59 patients with known screening status, only 44% (n = 26) had undergone screening. Patients of Black race, having stage III/IV disease, having Medicare/Medicaid insurance, and living within Baltimore City County were more likely to have family members with unknown or no screening. Lack of insurance coverage was the most common barrier, which was noted in 12.5% of patients (n = 3), whereas 54.1% of patients (n = 13) reported no barriers to screening. LIMITATIONS: Retrospective design. CONCLUSIONS: Most first-degree relatives of patients diagnosed with early-onset colorectal cancer do not undergo colorectal cancer screening. This could be attributed to the lack of protocols that could guarantee these individuals are informed of their elevated risk and the different options available for screening. Furthermore, our study suggests that racial and socioeconomic disparities exist among high-risk patients who should pursue screening. See Video Abstract . BAJAS TASAS DE DETECCIN DEL CNCER COLORRECTAL EN LOS FAMILIARES DE PRIMER GRADO DE NUESTROS PACIENTES LES ESTAMOS FALLANDO: ANTECEDENTES:Las directrices recomiendan realizar pruebas de detección a las personas con antecedentes familiares de cáncer colorrectal de aparición temprana a los 40 años o 10 años antes de la edad del diagnóstico de su familiar. Actualmente, no hay literatura que informe la tasa de detección en estos individuos y no existen protocolos para identificar y dirigirse a esta población para concientizar sobre la detección.OBJETIVO:Evaluar el cumplimiento de las pautas de detección actuales entre los FDR de pacientes con cáncer colorrectal de aparición temprana.DISEÑO:Estudio retrospectivo y cualitativo que incluyó una encuesta telefónica en la que se preguntó a los pacientes sobre el estado de detección de sus familiares y las barreras para la detección.AJUSTES:Dos instituciones comunitarias entre enero de 2018 y diciembre de 2021.PACIENTES:Personas diagnosticadas con cáncer colorrectal de inicio temprano que habían sido intervenidas quirúrgicamente en nuestras instituciones.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de detección en familiares de primer grado de nuestros pacientes con cáncer colorrectal de aparición temprana. Otros factores medidos incluyeron datos demográficos, características clínico-patológicas y barreras de detección.RESULTADOS:Se identificaron treinta y seis pacientes. La tasa de respuesta a la encuesta fue del 66,6% (n = 24). Resultaron un total de 88 familiares de primer grado que cumplieron con los criterios para la detección, y el 67,1% (n = 59) tenía un estado de detección conocido. De los 59 con estado de detección conocido, se informó que solo el 44% (n = 26) se había sometido a pruebas de detección. Los pacientes de raza afroamericana, enfermedad en etapa III/IV, Medicare/Medicaid y que vivían dentro del condado de la ciudad de Baltimore tenían más probabilidades de tener familiares con pruebas de detección desconocidas o sin ellas. La falta de cobertura de seguro fue la barrera más común observada por el 12,5% (n = 3); mientras que el 54,1% (n = 13) no informó ninguna barrera para el cribado.LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:La mayoría de los familiares de primer grado de pacientes diagnosticados con cáncer colorrectal de aparición temprana no se someten a pruebas de detección de cáncer colorrectal. Esto podría atribuirse a la falta de protocolos que garanticen que estas personas estén informadas sobre su elevado riesgo y las diferentes opciones disponibles para el cribado. Además, nuestro estudio sugiere que existen disparidades raciales y socioeconómicas entre los pacientes de alto riesgo que deberían someterse a pruebas de detección. (Traducción-Dr. Francisco M. Abarca-Rendon).

Paraproteinemic Neuropathies.

OBJECTIVE: Coexistence of polyneuropathy and gammopathy is a common but potentially challenging situation in clinical practice. This article reviews the clinical, electrophysiologic, and hematologic phenotypes of the paraproteinemic neuropathies and the diagnostic and treatment strategies for each. LATEST DEVELOPMENTS: Advances in our understanding of the underlying pathophysiology of various paraproteinemic neuropathies and their corresponding phenotypes have identified potential new therapeutic targets. Therapeutic strategies to diminish anti-myelin-associated glycoprotein (MAG) IgM antibodies have shown partial and inconsistent efficacy; however, antigen-specific immune therapy is being investigated as a novel treatment to remove the presumably pathogenic anti-MAG antibody. Advances in genetic and cell signaling studies have resulted in the approval of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia. Monoclonal antibodies are being investigated for the treatment of light chain amyloidosis. ESSENTIAL POINTS: Early recognition and treatment of underlying plasma cell disorders improves clinical outcomes in patients with paraproteinemic neuropathy. Despite significant progress, our knowledge regarding underlying mechanisms for paraproteinemic neuropathy is still limited. Clinicians' awareness of clinical phenotypes, electrophysiologic hallmarks, and hematologic findings of the different paraproteinemic neuropathies is crucial to promptly identify and treat patients and to avert misdiagnosis. Multidisciplinary collaboration among specialists, including neurologists and hematologists, is paramount for the optimal treatment of these patients with overlapping conditions.

Reducing body myopathy associated with the LIM2 p.(His123Arg) FHL1 variant.

Reducing body myopathy (RBM) is a rare muscle disorder, with marked presence of characteristic intracytoplasmic aggregates in affected muscle fibers. RBM is associated with FHL1 gene mutations. Clinical presentations of RBM have ranged from early fatal to adult onset progressive muscle weakness. We present herein the clinical, electrodiagnostic, and muscle biopsy findings of a 17-year-old female with progressive muscle weakness and contracture. Muscle biopsy showed atrophic fibers that contained menadione nitroblue tetrazolium (NBT) positive reducing bodies. Genetic testing revealed a variant of uncertain significance in the FHL1 gene at a position known to be pathogenic when substituted by other amino acids (p.His123Arg). This variant was later reclassified as pathogenic.

Non-communicable diseases in Lebanon: results from World Health Organization STEPS survey 2017.

OBJECTIVES: Non-communicable diseases (NCDs) are a major global health problem. The objective of the study was to estimate the prevalence of common risk factors for NCDs in Lebanon, both among the Lebanese population and Syrian refugees, aged 18-69 years, residing in communities. STUDY DESIGN: Two national cross-sectional surveys using a two-stage cluster sampling design were conducted among the Lebanese and Syrian refugee adults. METHODS: We used the World Health Organization (WHO) STEPwise approach through questionnaire assessment and physical and biochemical measurements. All reported results were weighted to provide prevalence estimates at the population level. RESULTS: A total of 1899 Lebanese and 2134 Syrians adults participated in the survey. More than one-third of participants were current smokers at the time of the assessment, and 23% of Lebanese participants were current drinkers (almost all Syrian refugees were lifetime abstainers). Vegetable and fruit consumption was rated moderately low, in 73% and 93% of Lebanese and Syrian refugees, respectively. Many respondents did not meet WHO recommendations on physical activity. More than one-third of participants had raised blood pressure or were on antihypertensive medications. One in 10 participants had either raised blood glucose level or were currently on glycemic control medications. For all risk factors and in both samples, women consistently had lower prevalence of NCD risk factors. CONCLUSIONS: Prevalence of risk factors for NCDs is high in Lebanon, and given the recent rise in population size, the financial and social burden of NCDs will grow dramatically in the next years. The results highlight the need for interventions to address behavioral changes, including reduction in smoking, improvement of dietary habits, optimization of management of diabetes and cardiovascular diseases, and conducting continuous surveillance to monitor the trends in NCD prevalence, their risk factors, and treatments.

Carbazole derivatives containing chalcone analogues targeting topoisomerase II inhibition: First principles characterization and QSAR modelling.

Recently, a series of carbazole derivatives containing chalcone analogues (CDCAs) were synthetized as potent anticancer agents and apoptosis inducers. These compounds target the inhibition of topoisomerase II and present cytotoxic activities. After comparison to experiment, we validated the use of B3LYP, a density functional theory-based approach, to describe the structure and molecular properties of the carbazole subunit and CDCAs compounds of interest. Then, we derived relationships between the chemical descriptors and activity of these carbazole derivatives using multi-parameter optimization and quantitative structure activity relationships (QSAR) approaches. For the QSAR studies, we used multiple linear regression and artificial neural network statistical modelling. Our predicted activities are in good agreement with the experimental ones. We found that the most important parameter influencing the activity of the considered compounds is the octanol-water partition coefficient, highlighting the importance of flexibility as a key molecular parameter to favor cell membrane crossing and enhance the action of these CDCAs against topoisomerase II. Our results provide useful guidelines for designing new oral active CDCAs medicaments for cytotoxic inhibition.

Minimal manifestation status and prednisone withdrawal in the MGTX trial.

OBJECTIVE: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG). METHODS: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups. RESULTS: Patients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone. CONCLUSIONS: Thymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone. CLINICALTRIALSGOV IDENTIFIER: NCT00294658. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone.

Gamma-Ray and Radio-Frequency Radiation from Thunderstorms Observed from Space and Ground.

Terrestrial gamma ray flashes (TGFs) are a class of enigmatic electrical discharges in the Earth's atmosphere. In this study, we analyze an unprecedentedly large dataset comprised of 2188 TGFs whose signatures were simultaneously measured using space- and ground-based detectors over a five-year period. The Gamma-ray Burst Monitor (GBM) on board the Fermi spacecraft provided the energetic radiation measurements. Radio frequency (RF) measurements were obtained from the Global Lightning Dataset (GLD360). Here we show the existence of two categories of TGFs - those that were accompanied by quasi-simultaneous electromagnetic pulses (EMPs) detected by the GLD360 and those without such simultaneous EMPs. We examined, for the first time, the dependence of the TGF-associated EMP-peak-amplitude on the horizontal offset distance between the Fermi spacecraft and the TGF source. TGFs detected by the GBM with sources at farther horizontal distances are expected to be intrinsically brighter and were found to be associated with EMPs having larger median peak-amplitudes. This provides independent evidence that the EMPs and TGFs are produced by the same phenomenon, rather than the EMPs being from "regular" lightning in TGF-producing thunderstorms.

Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial.

BACKGROUND: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. METHODS: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50-0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. FINDINGS: Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. INTERPRETATION: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Living-Donor Liver Transplantation in Hepatitis C Virus Era: A Report of 500 Consecutive Cases in a Single Center.

BACKGROUND: Living donor liver transplantation (LDLT) is considered a safe alternative to deceased donor liver transplantation (DDLT). In Egypt, DDLT program is still awaited, making LDLT the only hope for patients with end-stage liver disease, mainly due to chronic hepatitis C virus (HCV) infection. The current study is conducted to evaluate our experience of LDLT and discuss the lessons learned from 500 consecutive cases in HCV area. METHODS: We reviewed the data of patients who underwent LDLT at Gastrointestinal Surgery Center, Mansoura University during the period between May 2004 and March 2017. RESULTS: During the study period, 500 cases underwent LDLT at our unit. The median age was 51 years, and most of our cases were males (446, 89.2%) and had HCV infection (453, 90.6%). The median MELD score was 15. Median ICU stay was 5 days, and hospital stay was 22 days. Postoperative morbidities occurred in 220 cases (44%). Early mortality occurred in 69 patients (13.8%), and late mortality occurred in 45 patients (9%). The 1-, 3-, 5-, and 7-year overall survival rates of all cases were 80.9%, 78.2%, 75.7%, and 75%, respectively. Preoperative creatinine, worm ischemia, blood transfusion, ICU stay, postoperative morbidities, and small for size syndrome were independent predictors for overall survival. CONCLUSIONS: In countries lacking DDLT, LDLT is the only effective alternative. LDLT requires a teamwork to achieve successful outcomes. LDLT should only be performed in centers with the adequate experience to avoid and decrease the hazards related to this procedure.

Feline immunodeficiency virus and feline leukemia virus: frequency and associated factors in cats in northeastern Brazil.

Our aims were to determine the frequencies of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in owned and stray cats in the northeastern region of Brazil, ascertain the status of FeLV infection, and investigate potential associated factors among the owned cats. Blood samples from 200 asymptomatic owned cats and 30 stray cats were processed using nested PCR and commercial immunochromatographic tests to diagnose infections. To evaluate the factors associated with FIV and/or FeLV in owned cats, a semi-structured interview was conducted with each owner about the animal's environment, and these data were subjected to unconditional logistic regression. The frequencies for owned cats were 6% (12/200) and 3% (6/200) for FIV and FeLV, respectively. No owned cat was positive for both viruses. Stray cats showed frequencies of 6.66% (2/30) and 0% (0/30) for FIV and FeLV, respectively. Contact with other cats and living in peri-urban areas were considered to be risk factors (P < 0.05) for FIV. We did not identify any factors associated with infections with FeLV. Our results confirm the presence of these two retroviruses in the region under study. Our use of different diagnostic techniques allowed us to determine the frequency of retroviruses in the feline population more accurately, particularly with regard to infections by FeLV, which have complex pathogenesis.

Randomized Trial of Thymectomy in Myasthenia Gravis.

BACKGROUND: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS: A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS: Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).

Paraproteinemic neuropathy: a practical review.

The term paraproteinemic neuropathy describes a heterogeneous set of neuropathies characterized by the presence of homogeneous immunoglobulin in the serum. An abnormal clonal proliferation of B-lymphocytes or plasma cells, which may or may not occur in the context of a hematologic malignancy, produces the immunoglobulins in excess. If malignancy is identified, treatment should be targeted to the neoplasm. Most cases, however, occur as monoclonal gammopathy of undetermined significance. Few prospective, randomized, placebo-controlled trials are available to inform the management of paraproteinemic neuropathies. Clinical experience combined with data from smaller, uncontrolled studies provide a basis for recommendations, which depend on the specific clinical setting in which the paraprotein occurs. In this review, we provide a clinically practical approach to diagnosis and management of such patients.

Tocotrienol preserves ovarian function in cyclophosphamide therapy.

INTRODUCTION: Cyclophosphamide (CPA) chemotherapy leads to ovarian failure and infertility. Tocotrienol (T3) is an antioxidant and anti-inflammatory agent. The role of T3 in ovarian protection throughout chemotherapy remains unclear. AIM: To investigate the role of T3 in the preservation of female fertility in CPA treatment. METHOD: Sixty female mice were divided into five treatment groups, namely, normal saline, corn oil only, T3 only, CPA and CPA + T3. The treatment was given for 30 days, followed by administration of gonadotrophin to induce ovulation. After killing, both ovaries were collected and examined histologically. RESULTS: There was significant reduction in ovarian size in the CPA group compared with the normal group (CPA versus normal, mean area ± SD; 0.118 ± 0.018 vs. 0.423 ± 0.024 cm(2); p ≤ 0.005), whilst concurrent administration of T3 with CPA leads to conservation of ovarian size (CPA + T3 vs. CPA, mean area ± SD; 0.285 ± 0.032 vs. 0.118 ± 0.018 cm(2); p ≤ 0.005). Ovaries in CPA group showed abnormal folliculogenesis with accompanied reduced ovulation rate, follicular oedema, increased vascularity and inflammatory cell infiltration. These changes were reversed by concurrent T3 administration. CONCLUSION: Co-administration of T3 with CPA confers protection of ovarian morphology and function in vivo. These findings contribute to the further elucidation of CPA effect on ovary and suggest the potential of T3 use in preserving fertility in chemotherapy.

Myasthenia gravis associated with invasive malignant thymoma: two case reports and a review of the literature.

INTRODUCTION: Approximately ten to fifteen percent of patients with myasthenia gravis are found to have a thymoma, and twenty to twenty-five percent of patients with thymoma have myasthenia gravis. Thymomatous myasthenia gravis tends to have a difficult clinical course and poor prognosis. CASE PRESENTATION: We report two cases (one patient of Asian ethnicity and the other of Caucasian ethnicity) of atypical presentations of myasthenia gravis associated with invasive malignant thymoma. Both patients were diagnosed at a young age, in their 20s. They presented with a turbulent course of myasthenia gravis and recurrent thymoma, but obtained good outcome after aggressive treatment involving multiple different specialists. CONCLUSIONS: Although thymomatous myasthenia gravis tends to have a difficult clinical course and poor prognosis, early and aggressive treatment along with multidisciplinary management may improve the outcome of these patients.

The prognostic significance of left ventricular ejection fraction in patients with advanced cancer treated in phase I clinical trials.

BACKGROUND: New targeted agents may cause acute cardiac events. The purpose of our study was to investigate the incidence and the prognostic significance of left ventricular ejection fraction (LVEF) in phase I trials. PATIENTS AND METHODS: Between October 2008 and September 2011, the records of 1166 consecutive patients with advanced cancer treated in the Phase I Clinic who underwent echocardiography were retrospectively reviewed. RESULTS: Most of the patients were White (78%), and the most common tumor types were colorectal cancer and melanoma. Of 1166 patients, 177 (15.2%) patients had an LVEF of <50%. No difference in overall survival (OS) between patients with LVEF ≥ 50% and patients with LVEF < 50% was seen (median OS 7.4 versus 7.0 months, P = 0.84). Patients with LVEF ≤ 35% had shorter survival compared with those with LVEF between 35% and 50% (median 4.2 versus 8.0 months; P = 0.005). In multivariate analysis of patients with LVEF < 50%, independent factors predicting longer survival were LVEF > 35%, ≤2 prior systemic therapies, ≤2 metastatic sites, and normal lactate dehydrogenase and albumin levels. CONCLUSION: Echocardiography would improve patient selection for enrollment in phase I clinical trials. These data suggest that it is safe to treat patients with LVEF between 35% and 50%.

Delayed cervicobulbar neuronopathy and myokymia after head and neck radiotherapy for nasopharyngeal carcinoma: a case report.

INTRODUCTION: Delayed progressive cervicobulbar palsy with secondary lingual, facial, and neck myokymia after radiation therapy to the head and neck is a known but rare event with few reported case descriptions. CASE PRESENTATION: We report a case with a video description of a young Asian woman who developed progressive dysarthria and dysphagia after approximately 1 year after radiation treatment for nasopharyngeal carcinoma. Her symptoms, clinical, and electromyographic findings are discussed and were felt to be secondary to a cervicobulbar neuronopathy secondary to the previous radiation she received. A brief literature review was performed and pathophysiological mechanisms and treatment options are discussed. CONCLUSION: Delayed progressive cervicobulbar neuronopathy with myokymia is an uncommon complication of radiotherapy for nasopharyngeal carcinoma. Clinicians should be aware of this entity to prevent misdiagnosis with other neuromuscular and nonneuromuscular diseases.

Chronic immune-mediated demyelinating polyneuropathy in the setting of cetuximab treatment.

Cetuximab, a chimeric mouse/human monoclonal antibody directed against the epidermal growth factor receptor, is commonly used in colorectal and head and neck cancer. We describe an acquired neuropathy associated with cetuximab treatment in a patient with squamous cell carcinoma of the tongue. Our patient was treated with cetuximab from May to July 2008. In December 2008, he first noticed numbness in his feet. He progressed over the next 5 months to develop weakness in both legs, a lack of sensation up to his knees, pain in the dorsum of his feet with a burning sensation, and difficulty ambulating to the point of requiring a walker. He also had numbness in his fingertips and was unable to use his hands for fine movements. Electrodiagnostic studies demonstrated prolonged distal latencies, conduction block, and prolonged F-wave latencies, consistent with a diagnosis of definite CIDP according to EFNS/PNS criteria. Low amplitude potentials were noted in nerves of the lower extremities, indicative of secondary axonal loss. Extensive workup for an alternative cause was negative. He improved clinically after IVIG and corticosteroid treatment. We cannot strongly establish a causal relationship in this case, as 5 months elapsed between cetuximab treatment and the onset of neuropathic symptoms. Nonetheless, clinical vigilance is recommended when evaluating patients for neuropathy who have received cetuximab.

Imagem por ressonância magnética na investigação da cabeça de cães / Magnetic resonance imaging in the investigation of canine heads

A imagem por ressonância magnética (IRM) é o método de diagnóstico por imagem não invasivo mais sensível para avaliar as partes moles, particularmente o encéfalo, porém trata-se de uma técnica onerosa. O método fundamenta-se no fenômeno da ressonância magnética nuclear que ocorre quando núcleos atômicos com propriedades magnéticas presentes no corpo são submetidos a um campo magnético intenso, sendo posteriormente excitados por energia de radiofrequência e gerando, por sua vez, um sinal de onda de radiofrequência capaz de ser captado por uma antena receptora, passando por um processo matemático, chamado Transformada de Fourier, para posterior formação da imagem. Esse estudo objetivou realizar 10 exames completos da cabeça em cadáveres de cães normais à IRM e confeccionar um Atlas com as estruturas identificadas. As imagens foram adquiridas em um aparelho de ressonância magnética Gyroscan S15/HP Philips com campo magnético de 1,5Tesla. Os cadáveres foram posicionados com a cabeça no interior de uma bobina de cabeça humana e foram submetidos a cortes iniciais sagitais a partir de onde se planejou os cortes transversais e dorsais nas sequências de pulso spin-eco T1, T2 e DP. Em T1 utilizou-se TR=400ms e TE=30ms, T2 utilizou-se TR=2000ms e TE=80ms e na DP utilizou-se TR=2000ms e TE=30ms. A espessura do corte foi de 4mm, o número de médias foi igual a 2, a matriz foi de 256x256, o fator foi igual a 1,0 e o campo de visão foi de 14cm. A duração do exame completo da cabeça foi de 74,5minutos. As imagens obtidas com as sequências utilizadas e com a bobina de cabeça humana foram de boa qualidade. Em T1 a gordura tornou-se hiperintensa e o líquido hipointenso. Em T2 a gordura ficou menos hiperintensa e o líquido hiperintenso. A cortical óssea e o ar foram hipointensos em todas as sequências utilizadas devido a baixa densidade de prótons...

Magnetic resonance imaging (MRI) is the most sensitive method of diagnostic imaging to evaluate soft tissues, specially the brain, however it is expensive. The method is based on the nuclear magnetic resonance phenomenon that occurs when atomic nucleus with magnetic proprieties in the body are submitted to a strong magnetic field, and excited with radio frequency generating a radio frequency signal captured by a receptive antenna. The signal is processed by Fourier Transform for the image formation. This study had the objective to obtain 10 complete exams of heads in cadavers of normal dogs to MRI and to make an Atlas of head structures. The images were obtained with a magnetic resonance unit Gyroscan S15/HP Philips using a magnetic field of 1,5Tesla. The cadavers were positioned with the head into a human head coil and submitted to sagittal slices used to plan transverse and dorsal slices in T1, T2 and DP spin-echo sequences. In T1 we adjusted TR=400ms and TE=30ms, in T2 TR=2000ms and TE=80ms and in DP TR=2000ms and TE=30ms. The slice thickness was 4mm, the number of averages 2, the matrix 256x256, the factor 1,0 and the field of view 14cm. The duration of the complete exam of the head was 74,5minutes. The images obtained with the described sequences and with the human head coil was of good quality. In T1 fat was hyperintense and fluid was hypointense. In T2 fat was less hyperintense and fluid was hyperintense. The cortical bone and the air were hypointense in all sequences used because of the low proton density. The DP sequence showed the best contrast between white and gray matter when compared with T2 and T1 sequences...

Nanoparticulate cellular patches for cell-mediated tumoritropic delivery.

The targeted delivery of therapeutics to tumors remains an important challenge in cancer nanomedicine. Attaching nanoparticles to cells that have tumoritropic migratory properties is a promising modality to address this challenge. Here we describe a technique to create nanoparticulate cellular patches that remain attached to the membrane of cells for up to 2 days. NeutrAvidin-coated nanoparticles were anchored on cells possessing biotinylated plasma membrane. Human bone marrow derived mesenchymal stem cells with nanoparticulate patches retained their inherent tumoritropic properties as shown using a tumor model in a 3D extracellular matrix. Additionally, human umbilical vein endothelial cells with nanoparticulate patches were able to retain their functional properties and form multicellular structures as rapidly as unmodified endothelial cells. These results provide a novel strategy to actively deliver nanostructures and therapeutics to tumors utilizing stem cells as carriers and also suggest that nanoparticulate cellular patches may have applications in tissue regeneration.