Underreporting and Underrepresentation of Racial and Ethnic Minority Patients in Lymphedema Clinical Trials: A Systematic Review.

The generalizability of findings from Clinical Trials (CTs) investigating lymphedema treatment modalities requires an accurate representation of the target population. This study aims to evaluate racial and ethnic reporting and representation in lymphedema CTs. A comprehensive systematic literature search was conducted during May 2023 using multiple databases, following the PRISMA guidelines. All CTs published from 2018 to 2023 were included. A total of 84 articles were included in this review, from which 6,546 participants were included in the analysis. Seventy-four (88.1%) articles addressed secondary lymphedema, of which 60 (81.1%) were related to breast cancer. Only 12 (13%) of CTs reported at some extend race or ethnicity. Of these, five (41.6%) reported race and two (16.6%) reported ethnicity according to FDA guidelines. White race had the highest pooled prevalence (80%; 95% CI 72-86%; I2=90%), followed by Black (7%; 95% CI 2- 15%; I2= 94.3%) and Asian (4%; 95% CI 1-8%; I2= 89.9%). In studies reporting ethnicity, participants were predominantly non-Hispanic (92.1%; 95% CI 90 - 94%). There is an underreporting and underrepresentation of racial and ethnic minorities among lymphedema CTs, limiting their generalizability. It is imperative to future development of strategies to enhance diversity in the study sample.

Long-term treatment with nebulized colistin in oncological patients with recurrent respiratory infections.

OBJECTIVES: To assess the efficacy of long-term treatment with nebulized colistin in reducing the number of respiratory infections, emergency consultations and hospitalizations in oncological patients. METHODS: A retrospective, observational, single-centre study including patients with solid or haematologic malignancies, or pulmonary GVHD after HSTC who received treatment with nebulized colistin for at least six-months to prevent recurrent respiratory infections (July 2010 to June 2017). RESULTS: Twelve patients were included (median age: 54.4, range: 23-85), 7 with solid malignancies and 5 with haematologic malignancies (2 with pulmonary GVHD). Pseudomonas aeruginosa was the most frequent microorganism in sputum cultures (11/12 patients), all strains were susceptible to colistin. There was a statistically significant reduction (p=0.01) in respiratory infections in the six-month period after starting colistin (median: 1, range: 0-4) compared to the six-month period before (median: 4, range: 1-8). There was also a reduction in emergency consultations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) and hospitalizations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) due to respiratory infections. No colistin-resistant strains were identified. CONCLUSIONS: Long-term treatment with nebulized colistin may be useful to reduce the number of exacerbations in oncological patients with recurrent respiratory infections.

Reliability of a computer-aided system in the evaluation of indeterminate ultrasound images of thyroid nodules.

Introduction: Computer-aided diagnostic (CAD) programs for malignancy risk stratification from ultrasound (US) imaging of thyroid nodules are being validated both experimentally and in real-world practice. However, they have not been tested for reliability in analyzing difficult or unclear images. Methods: US images with indeterminate characteristics were evaluated by five observers with different experience in US examination and by a commercial CAD program. The nodules, on which the observers widely agreed, were considered concordant and, if there was little agreement, not concordant or difficult to assess. The diagnostic performance of the readers and the CAD program was calculated and compared in both groups of nodule images. Results: In the group of concordant thyroid nodules (n = 37), the clinicians and the CAD system obtained similar levels of accuracy (77.0% vs 74.2%, respectively; P = 0.7) and no differences were found in sensitivity (SEN) (95.0% vs 87.5%, P = 0.2), specificity (SPE) (45.5 vs 49.4, respectively; P = 0.7), positive predictive value (PPV) (75.2% vs 77.7%, respectively; P = 0.8), nor negative predictive value (NPV) (85.6 vs 77.7, respectively; P = 0.3). When analyzing the non-concordant nodules (n = 43), the CAD system presented a decrease in accuracy of 4.2%, which was significantly lower than that observed by the experts (19.9%, P = 0.02). Conclusions: Clinical observers are similar to the CAD system in the US assessment of the risk of thyroid nodules. However, the AI system for thyroid nodules AmCAD-UT® showed more reliability in the analysis of unclear or misleading images.

Preoperative hepatic artery embolization before distal pancreatectomy plus celiac axis resection does not improve surgical results: A Spanish multicentre study.

BACKGROUND: Distal pancreatectomy with celiac axis resection (DP-CAR) is a surgical procedure with high morbidity and mortality performed in patients with locally advanced pancreatic cancer. Preoperative embolization of hepatic artery (PHAE) has been postulated as a technical option to increase resection rate. OBJECTIVE: comparison of morbidity and mortality at 90 days, operative time, hospital stay and survival between patients that performed DP-CAR with and without PHAE. METHODS: Observational retrospective multicentre study. INCLUSION CRITERIA: patient operated in Spanish centers with DP-CAR for pancreatic cancer from April 2004 until 23 June 2018. Preoperative (PHAE, neodjuvant treatment), intraoperative (operative time and blood loss) and postoperative data (morbidity, hospital stay, R0 and survival) were studied. Complications were measured with Clavien classification at 90 days. Specific pancreatic complications were measured using ISGPS classifications. Data were analyzed using R version 3.1.3 (http://www.r-project.org). Level of significance was set at 0.05. RESULTS: 41 patients were studied. 26 patients were not embolized (NO-PHAE group) and 15 patients received PHAE. Preoperative BMI and percentage of neoadjuvant chemotherapy were the only preoperative variables different between both groups. The operative time in the PHAE group was shorter (343 min) than in the non-PHAE group (411 min) (p < 0.06). Major morbidity (Clavien > IIIa) and mortality at 90 days were higher in the PHAE group than in the non-PHAE group (60% vs 23% and 26.6% vs 11.6% respectively) (p < 0.004). No statistical difference in overall survival was observed between both groups (p = 0.14). CONCLUSION: In our study PHAE is not related with less postoperative morbidity. Even more, major morbidity (Clavien III-IV) and mortality was higher in PHAE group.

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. METHODS: Observational retrospective multicenter study. INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.

Differences in the clinical management of women and men after detection of a solitary pulmonary nodule in clinical practice.

OBJECTIVES: To explore differences in the clinical management of men and women in the 5 years after detecting a solitary pulmonary nodule (SPN) by chest radiograph or CT in routine clinical practice. METHODS: We followed up 545 men and 347 women with an SPN detected by chest radiograph or CT in a retrospective cohort of 25,422 individuals undergoing routine thoracic imaging in 2010-2011. We compared the frequency of each management strategy (no further test, immediate intervention or follow up) according to sex by means of chi-squared. We estimated the relative risk of women versus men of having been followed up instead of an immediate intervention using multivariate logistic regression. We compared by sex the time between detection of the nodule and lung cancer diagnosis, the time between diagnosis and death by means of Mann-Whitney U test and the cumulative effective dose of radiation in each management strategy by means of t test. RESULTS: Women were more likely than men to have follow-up rather than immediate intervention (aRR = 1.8, CI 1.3-2.7, p = 0.002), particularly in those who underwent CT (aRR = 4.2, CI 1.9-9.3, p < 0.001). The median time between SPN detection and lung cancer diagnosis was higher in women (4.2 months, interquartile range (IQR) 5.1) than in men (1.5 months, IQR 16.2). The mean cumulative effective dose was 21.3 mSv, 19.4 mSv in men and 23.9mv in women (p = 0.023). CONCLUSIONS: Our results could reflect decisions based on a greater suspicion of lung cancer in men. The incidental detection of SPNs is increasing, and it is necessary to establish clear strategies aimed to reduce variability in their management according to patient's sex. KEY POINTS: • After incidental finding of SPN, women were less likely to receive an immediate intervention. • Accumulative radiation was higher in women than in men. • Our results could reflect decisions based on a greater suspicion of lung cancer in men.

The determinants of lung cancer after detecting a solitary pulmonary nodule are different in men and women, for both chest radiograph and CT.

OBJECTIVES: To determine the factors associated with lung cancer diagnosis and mortality after detecting a solitary pulmonary nodule (SPN) in routine clinical practice, in men and in women for both chest radiograph and CT. MATERIALS AND METHODS: A 5-year follow-up of a retrospective cohort of of 25,422 (12,594 men, 12,827 women) patients aged ≥35 years referred for chest radiograph or CT in two hospitals in Spain (2010-2011). SPN were detected in 893 (546 men, 347 women) patients. We estimated the cumulative incidence of lung cancer at 5-years, the association of patient and nodule characteristics with SPN malignancy using Poisson logistic regression, stratifying by sex and type of imaging test. We calculated lung cancer specific mortality rate by sex and SPN detection and hazard rates by cox regression. RESULTS: 133 (14.9%) out of 893 patients with an SPN and 505 (2.06%) of the 24,529 patients without SPN were diagnosed with lung cancer. Median diameter of SPN in women who developed cancer was larger than in men. Men who had a chest radiograph were more likely to develop a lung cancer if the nodule was in the upper-lobes, which was not the case for women. In patients with an SPN, smoking increased the risk of lung cancer among men (chest radiograph: RR = 11.3, 95%CI 1.5-83.3; CT: RR = 7.5, 95%CI 2.2, 26.0) but smoking was not significantly associated with lung cancer diagnosis or mortality among women with an SPN. The relative risk of lung cancer diagnosis in women with SPN versus those without was much higher compared to men (13.7; 95%CI 9.2, 20.4 versus 6.2; 95%CI 4.9,7.9). CONCLUSION: The factors associated with SPN malignancy and 5-year lung cancer mortality were different among men and women, especially regarding smoking history and SPN characteristics, where we observed a relatively high rate of lung cancer diagnosis among female non-smokers.

Why don't corticotroph tumors always produce Cushing's disease?

OBJECTIVE: Silent corticotroph tumors are a pituitary neuroendocrine tumor subtype of corticotroph lineage that do not clinically express Cushing's disease. The silencing of this type of tumor is not fully understood. The aim of the present study was to delve into the lack of secretory activity, studying the post-transcriptional and post-translational regulation of POMC/ACTH in a series of molecularly identified functioning and silent corticotroph tumors. DESIGN: We analyzed 24 silent corticotroph, 23 functioning corticotroph and 25 silent gonadotroph tumors. METHODS: We used Sanger sequencing, quantitative real-time PCR and Western blot to analyze genetic alterations in POMC, gene expression of TBX19, NEUROD1, POMC, PCSK1, PCSK2, CPE and PAM and protein expression of POMC, PC1/3, PC2, CPE and PAM. RESULTS: We found different polymorphisms in the POMC gene of corticotroph tumors, some of them related to deficiency of proopiomelanocortin. Silent corticotroph tumors showed lower PC1/3 gene and protein expression than functioning ones, especially compared to micro-functioning corticotroph tumors (all P < 0.05). Moreover, we found a positive correlation between PC2 and CPE gene and protein expression (rho ≥ 0.670, P < 0.009) in silent corticotroph tumors compared with functioning ones. CONCLUSIONS: By studying the post-transcriptional and post-translational processing of POMC and ACTH, respectively, in a large series of silent and functioning corticotroph tumors, we found that the lack of secretory activity of these tumors is related to an impaired processing of POMC and a high degradation of ACTH, with the macro-functioning corticotroph tumor behaving as an intermediate state between micro-functioning and silent corticotroph tumors.

Intracellular Delivery of Biologically-Active Fungal Metabolite Gliotoxin Using Magnetic Nanoparticles.

Gliotoxin (GT), a secondary metabolite produced by Aspergillus molds, has been proposed as a potential anti-tumor agent. Here we have developed a nanoparticle approach to enhance delivery of GT in tumor cells and establish a basis for its potential use as therapeutical drug. GT bound to magnetic nanoparticles (MNPs) retained a high anti-tumor activity, correlating with efficient intracellular delivery, which was increased in the presence of glucose. Our results show that the attachment of GT to MNPs by covalent bonding enhances intracellular GT delivery without affecting its biological activity. This finding represents the first step to use this potent anti-tumor agent in the treatment of cancer.

[What do MRI and CT scan provide us in patients with vertigo and dizziness? A cost-utility analysis]. / Que aporta la neuroimagen en pacientes con vertigo y mareo? Analisis coste-utilidad.

INTRODUCTION: Vertigo and dizziness are symptoms with a significant burden in the hospital and involve several specialties. There are few guidelines of radiological tests for these symptoms. AIMS: To know which profile of patients with vertigo and dizziness has neuroimaging tests, quantify and describe the radiological findings. To analyze the cost-utility of CT and MRI in the study of these patients. PATIENTS AND METHODS: Descriptive study, we selected patients referred to the hospital for vertigo and dizziness. We analyze demographic and clinical characteristics and quantify the neuroimaging tests requested. We describe the radiological findings, assess their relevance in the diagnosis and detail the cost-benefit. RESULTS: We identified 493 patients, those with neuroimaging test (60%) are older, depressed and frequented the emergency department because of vertigo. The most requested test was the cranial CT scan (5% identifies the cause of the symptom). MRI of the inner ear and cerebellopontine angle was the test that presented the most significant findings (17.7%). The 286 image tests requested for vertigo cost 56,741 euros. The cost for a positive test was 1,576 euros. CONCLUSIONS: A large number of head CT and MRI are made in patients with vertigo and dizziness. A clinical suspicion is recommended from the anamnesis and exploration to make a good selection of test to request. In more than 90% of cases, radiological findings are not shown in relation to vertigo.

TITLE: Que aporta la neuroimagen en pacientes con vertigo y mareo? Analisis coste-utilidad.Introduccion. Vertigo y mareo son sintomas que suponen una carga significativa en el hospital e involucran a varias especialidades. Existen pocas guias sobre la solicitud de pruebas radiologicas ante estos sintomas. Objetivos. Conocer que perfil de pacientes con vertigo y mareo tiene realizadas pruebas de neuroimagen, cuantificar y describir los hallazgos radiologicos, y analizar el coste-utilidad de la tomografia computarizada (TC) y la resonancia magnetica (RM) en pacientes con estos sintomas. Pacientes y metodos. Estudio descriptivo en el que se seleccionan pacientes remitidos al hospital por vertigo y mareo. Se analizan caracteristicas demograficas y clinicas y se cuantifican las pruebas de neuroimagen solicitadas. Se describen los hallazgos radiologicos, se valora su relevancia en el diagnostico y se detalla el coste. Resultados. Se identifica a 493 pacientes, el 60% tiene realizada una prueba de neuroimagen; son pacientes de mas edad, depresivos y que han acudido a urgencias por vertigo. La prueba mas realizada fue la TC de craneo sin contraste (el 5% identifica la causa del sintoma). La que presento mas hallazgos significativos fue la RM de la base del craneo (17,7%). Las 286 pruebas de imagen solicitadas por vertigo costaron 56.741 euros. El gasto para obtener un diagnostico radiologico fue de 1.576 euros. Conclusiones. Se realiza un gran numero de TC y RM de cabeza en pacientes con vertigo y mareo. Es recomendable tener un diagnostico de sospecha previo a partir de la anamnesis y la exploracion para hacer una buena seleccion de las pruebas que hay que solicitar. En mas del 90% de los casos no se muestran hallazgos radiologicos en relacion con el vertigo.

Effect of preoperative creatinine levels on mortality after coronary artery bypass grafting surgery: an observational study

Abstract Introduction: Renal function is an independent risk factor for mortality among on-pump coronary bypass grafting (ONCABG) patients. This association is well known in the international literature, but there is a lack of knowledge of how admission creatinine (AC) levels modulate each cardiovascular risk factor. Objective: The aim of this paper was to assess the effect of different AC levels on mortality among ONCABG patients. Methods: 1,599 patients who underwent ONCABG between December 1999 and February 2006 at Hospital de Base in São José do Rio Preto/SP-Brazil were included. They were divided into quartiles according to their AC levels (QI: 0.2 ≤AC < 1.0 mg/dL; QII: 1.0 ≤ AC < 1.2 mg/dL; QIII: 1.2 ≤ AC < 1.4 mg/dL; and QIV: 1.4 ≤ AC ≤ 2.6 mg/dL). Seven risk factors were then evaluated in each stratum. Results: Mortality was higher in the QIV group than QI or QII groups. Factors such as age (≥ 65 years) and cardiopulmonary bypass (CPB) time (≥ 115 minutes) in QIV, as well preoperative hospital stay (≥ 5 days) in QIII, were associated with higher mortality rates. Creatinine variation greater than or equal to 0.4 mg/dL increased mortality rates in all groups. The use of intra-aortic balloon pump and dialysis increased mortality rates in all groups except for QII. Type I neurological dysfunction increased the mortality rate in the QII and III groups. Conclusion: Creatinine levels play an important role in ONCABG mortality. The combination of selected risk factors and higher AC values leads to a worse prognosis. On the other hand, lower AC values were associated with a protective effect, even among elderly patients and those with a high CPB time.