Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. RESULTS: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. CONCLUSIONS: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.

Plasma lipids, tumor parameters and survival in HCC patients with HBV and HCV.

INTRODUCTION AND AIMS: Hepatocellular carcinoma (HCC) is a consequence of chronic liver disease, particularly from hepatitis B or C and increasingly from obesity and metabolic syndrome. Since lipids are an important component of cell membranes and are involved in cell signaling and tumor cell growth, we wished to evaluate the relationship between HCC patient plasma lipids and maximum tumor diameter and other indices of HCC human biology. METHODS: We examined prospectively-collected data from a multi-institutional collaborative Turkish HCC working group, from predominantly HBV-based patients, for plasma lipid profiles, consisting of triglycerides, total cholesterol, LDL-cholesterol (LDL) and HDL-cholesterol (HDL) and compared these with the associated patient maximum tumor diameter (MTD), portal vein thrombosis, alpha-fetoprotein (AFP) and also with patient survival. RESULTS: We found that both low HDL (p=0.0002) and high LDL (p=0.003) levels were significantly associated with increased MTD, as well as in a final multiple linear regression model on MTD. The combination of low HDL combined with high HDL levels were significant in a regression model on MTD, PVT and an HCC Aggressiveness Index (Odds Ratio 12.91 compared to an Odds Ratio of 1 for the reference). Furthermore, in a Cox regression model on death, the HDL plus LDL combination had a significantly higher Hazard Ratio than the reference category. CONCLUSIONS: Low plasma HDL, high plasma LDL and especially the combination, were significantly related to more aggressive HCC phenotype and the combination was significantly related to a higher Hazard Ratio for death.

Tumor multifocality and serum albumin levels can identify groups of patients with hepatocellular carcinoma and portal vein thrombosis having distinct survival outcomes.

BACKGROUND: Macroscopic portal vein thrombosis (PVT) is a major poor prognosis factor in patients with hepatocellular carcinoma (HCC), but constitute a heterogeneous group. AIMS: To examine blood and tumor parameters of 1667 HCC patients who had PVT to identify factors that could differentiate different survival subsets. METHODS: a large HCC database was examined for presence of patients with PVT and analyzed retrospectively for PVT-associated factors and prognosis. RESULTS: A logistic regression model was calculated for presence of PVT. Highest odds ratios were found for tumor multifocality and serum albumin levels, as well as serum alpha-fetoprotein (AFP) and bilirubin levels. A Kaplan-Meier and Cox model on survival also showed the highest hazard ratios for tumor multifocality and serum albumin. A model was constructed on all 4 possible combinations of tumor focality and serum albumin in PVT patients. The longest survival group had <2 tumor nodules plus serum albumin >3.5 g/dL. Conversely, the shortest survival group had >2 tumor nodules plus serum albumin <3.5 g/dL. These 2 patient groups differed in maximum tumor diameter and levels of serum AFP, AST and bilirubin. CONCLUSIONS: Combination low tumor focality and high serum albumin identifies prognostically better PVT patient subgroups that might benefit from aggressive therapies.

Radiotherapy in cancer and rheumathoid arthritis patients: cancer treatment or control of articular flares? We can achieve both.

OBJECTIVE: The study was aimed to investigate the role of radiotherapy (RT) as a risk factor for reactivation or worsening of symptoms in patients affected by rheumatoid arthritis (RA) PATIENTS AND METHODS: This is a single-center retrospective observational study on RA patients who developed cancer requiring RT during the course of the disease. The control group consisted of RA patients with cancer who did not undergo RT. In both groups, the disease activity was evaluated at baseline and at 6 and 12 months through the DAS28 index. A relapse was defined as an increase of >20% in DAS28. A radiotherapist evaluated total and daily doses and timing of radiation. Acute and late toxicity was defined as events occurring within 90 days from the start and more than 90 days after the completion of RT, respectively. RESULTS: Seventy-two RA patients (38F/34M; mean age: 70±9 years; mean disease duration: 13±9 years), 29 (40.2%) of whom received radiotherapy (mean age 72.9±9 years), were enrolled. The most frequent malignancies were breast (27.2%), thyroid (9.8%), and skin (7%). Between radio-treated and non-radio-treated patients, no significant differences in RA reactivation (6/29 vs. 17/43; p=0.12) or mean exacerbation time (6.7 ± 4.9 months compared to 6.4 ± 4.1 months; p=0.78) were found. Overall, RT was well tolerated with low rates of both acute and late toxicity. CONCLUSIONS: In RA patients, RT was well tolerated and not associated with an increased risk of articular flares. Properly designed prospective clinical studies with a larger number of patients should be performed to confirm these data.

Trends in Tumor Indices in Relation to Increased Hepatocellular Carcinoma Size: Evidence for Tumor Evolution as a Function of Growth.

BACKGROUND: The prognosis of HCC depends in large measure on maximum tumor diameter (MTD). AIMS: To examine characteristics of tumor aggressiveness over an MTD range of < 2 to 8 cm. METHODS: A large HCC database was examined retrospectively for trends in serum alpha-fetoprotein (AFP), and percent of patients with macroscopic portal vein thrombosis (PVT) or tumor multifocality. RESULTS: There was a significant trend to increased serum AFP levels and percent of patients with PVT, for each, p < 0.001. Within those trends, there were clearly identifiable sub-trends for variations of AFP or percent PVT patients, associated with specific MTD ranges. Calculation of the fold increase for either AFP or percent PVT patients over distinct MTD ranges showed a greater increase of AFP or percent PVT patients compared with the related MTD increase. Interestingly, the increase in percent PVT was mainly independent of AFP. CONCLUSIONS: Patterns of AFP and PVT increase can be discerned with increasing MTD, which are nonlinear. The greater fold increase in tumor aggressiveness factors compared with MTD suggests that HCCs may change with increasing size to a more aggressive phenotype. Baseline HCC biopsies might therefore be insufficient in future rational HCC management, and repeated liquid biopsies have potential in following HCC evolution and thus choices of therapies.

Portal Vein Thrombosis and Markers of Inflammation in Hepatocellular Carcinoma.

BACKGROUND: Macroscopic portal vein thrombosis (PVT) is a major poor prognosis factor in patients with hepatocellular carcinoma (HCC). Inflammation is increasingly recognized to be part of the hepatocarcinogenic process and its markers are also prognostically useful. AIMS: To examine the relationship of inflammation biomarkers to the presence of PVT and to survival in PVT patients with HCC. METHODS: A large HCC cohort was examined for the presence of PVT and analyzed retrospectively. RESULTS: Blood levels of NLR, PLR, ESR, CRP, AFP and GGTP were significantly related to the presence of PVT, but not the Glasgow Index. For patients with low alpha-fetoprotein levels, blood ESR and GGTP levels were also significantly increased in patients with PVT compared with those in patients without PVT. In a Cox regression model, serum GGTP levels had a significantly increased hazard ratio on death (1.52, p = 0.008). Kaplan-Meier analysis showed that PVT patients with low serum GGTP levels had significantly longer survival than PVT patients with high GGTP levels (p = 0.0041). CONCLUSIONS: Indices of inflammation, especially serum GGTP levels, related significantly to the presence of PVT and to survival in HCC patients with PVT.

Dietary inflammatory index and mortality: a cohort longitudinal study in a Mediterranean area.

BACKGROUND: Higher Dietary Inflammatory Index (DII®) scores are associated with increased morbidity and mortality. However, little is known about the effects of DII on mortality in Mediterranean countries. Therefore, in the present study, we aimed to investigate the potential association between DII scores and overall, cancer and cardiovascular disease (CVD) mortality in people living in a Mediterranean area. METHODS: DII scores were calculated using a validated food-frequency questionnaire. DII scores were then categorised into tertiles. Mortality was ascertained via death certificates. The association between DII scores with overall and cause-specific mortality was assessed via a multivariable Cox's regression analysis and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs). RESULTS: The study included 1565 participants (mean age 65.5 years; females 44.7%). After a median follow-up of 12 years (2005-2017), 366 (23.4%) participants died. After adjusting for 17 potential confounders, people with higher DII scores had an increased risk of death compared to those in the lowest (most anti-inflammatory) tertile (HR = 1.38; 95% CI = 1.04-1.82 for the second tertile; HR = 1.38; 95% CI = 1.03-1.86 for the third tertile). Each 1 SD increase in DII score increased the risk of death by 13%. No association was found between DII scores and cancer or CVD death when considered separately. CONCLUSIONS: Higher DII scores were associated with a significantly higher mortality risk, whereas the association with cause-specific mortality was less clear. These findings highlight the potential importance of diet in modulating inflammation and preventing death.

Polivictimización y su relación con las conductas autoagresivas y con la depresión en adolescentes / Polyvictimization and its relation with self-aggressive behaviors and with depression in adolescents

Resumen Introducción: La acumulación de experiencias de distinto tipo de maltrato o violencia durante la infancia ha sido nominada como polivictimización. Se ha documentado que la polivictimización genera consecuencias negativas en la salud mental de las personas. En Chile, no existe suficiente investigación respecto de este fenómeno, únicamente se conocen algunas cifras que muestran que es prevalente. El objetivo del estudio es evaluar la frecuencia con que adolescentes han sido sometidos a diferentes niveles de polivictimización y su relación con los niveles de sintomatología depresiva y con la frecuencia de conductas autolesivas. Método: El estudio, descriptivo correlacional, encuesta a 114 adolescentes de entre 17 y 18 años de edad. Resultados: Se aprecia que el 40,3% de la muestra habría sufrido al menos 2 tipos diferentes de victimización y que la polivictimización se asocia a la sintomatología depresiva y a la frecuencia de las autoagresiones. Conclusión: Se concluye que los profesionales de salud mental debieran evaluar la posibilidad de que la psicopatología de sus pacientes específicos pudiese estar relacionados con experiencias de victimización infantojuvenil que debieran ser consideradas en los tratamientos.

Introduction: The accumulation of experiences of abuse or violence during childhood has been nominated as a polyvictimization. It has been documented that the polyvictimización generates negative consequences in the mental health of the people. In Chile there is not enough research on this phenomenon, only there is known that it is prevalent. The objective of the study is to evaluate the frequency of polyvictimization in the adolescents and its relation with the levels of depressive symptomatology and with the frequency of self-injurious behaviors. Method: This is a descriptive correlational study. We survey 114 adolescents between 17 and 18 years of age. Results: It was observed that 40.3% of the sample had suffered at least 2 different types of victimization and that polyvictimization is associated with depressive symptoms and with the frequency of self-harm. Conclusion: It is concluded that mental health professionals should evaluate the possibility that the mental health problems of their specific patients may be related to experiences of child and adolescent victimization, which should be considered in the treatments.

Potato Consumption Is not Associated with Higher Risk of Mortality: A Longitudinal Study among Southern Italian Older Adults.

OBJECTIVE: The consumption of potatoes is increasing worldwide, but few studies have assessed the association between potato consumption and mortality, particularly in Mediterranean countries. We therefore investigated whether potato consumption is associated with higher risk of death in a large cohort of people living in South Italy. DESIGN: Longitudinal. SETTING: Community-dwelling. MEASUREMENTS: 2,442 participants coming from MICOL and NUTRIHEP studies aged more than 50 years at baseline were followed-up for 11 years. Dietary intake was assessed by means of a Food Frequency Questionnaire. Potato consumption was categorized in quintiles according to their daily consumption (< 3.95, 3.96-8.55, 8.56-15.67, 15.68-22.0, and > 22.0 g/day). Mortality was ascertained through validated cases of death. The association between potato consumption and mortality was assessed through Cox's regression models, adjusted for potential confounders, and reporting the data as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The 2,442 eligible participants were prevalently males (54.6%) and aged a mean of 64.3±9.3 years. During the 11-year follow-up, 396 (=16.2%) participants died. After adjusting for 12 potential baseline confounders, and taking those with the lowest consumption of potatoes as the reference group, participants with the highest consumption of potatoes did not have an increased overall mortality risk (HR=0.75; 95%CI: 0.53-1.07). Modelling the potato consumption as continuous (i.e. as increase in 10 g/day) did not substantially change our findings (fully-adjusted HR=0.93; 95%CI: 0.84-1.02). CONCLUSION: Overall potato consumption was not associated with higher risk of death in older people living in a Mediterranean area. Future studies are warranted to elucidate the role of potato consumption on all-cause and cause-specific mortality.

Right ventricular function during exercise in children after heart transplantation.

Aims: Right ventricular (RV) dysfunction is a common problem after heart transplant (HTx). In this study, we used semi-supine bicycle ergometry (SSBE) stress echocardiography to evaluate RV systolic and diastolic reserve in paediatric HTx recipients. Methods and results: Thirty-nine pediatric HTx recipients and 23 controls underwent stepwise SSBE stress echocardiography. Colour tissue doppler imaging (TDI) peak systolic (s') and peak diastolic (e') velocities, myocardial acceleration during isovolumic contraction (IVA), and RV free wall longitudinal strain were measured at incremental heart rates (HR). The relationship with increasing HR was evaluated for each parameter by plotting values at each stage of exercise versus HR using linear and non-linear regression models. At rest, HTx recipients had higher HR with lower TDI velocities (s': 5.4 ± 1.7 vs. 10.4 ± 1.8 cm/s, P < 0.001; e': 6.4 ± 2.2 vs.12 ± 2.4 cm/s, P < 0.001) and RV IVA values (IVA: 1.2 ± 0.4 vs. 1.6 ± 0.8 m/s2, P = 0.04), while RV free wall longitudinal strain was similar between groups. At peak exercise, HR was higher in controls and all measurements of RV function were significantly lower in HTx recipients, except for RV free wall longitudinal strain. When assessing the increase in each parameter vs. HR, the slopes were not significantly different between patients and controls except for IVA, which was lower in HTx recipients. Conclusion: In pediatric HTx recipients RV systolic and diastolic functional response to exercise is preserved with a normal increase in TDI velocities and strain values with increasing HR. The blunted IVA response possibly indicates a mildly decreased RV contractile response but it requires further investigation.

Rectal indomethacin or intravenous gabexate mesylate as prophylaxis for acute pancreatitis post-endoscopic retrograde cholangiopancreatography.

OBJECTIVE: We aimed to evaluate the results in our case series of AP ERCP over the last three years. The prophylaxis for acute pancreatitis (AP) post-endoscopic retrograde cholangiopancreatography (ERCP) consists of rectal indomethacin, but some studies are not concordant. PATIENTS AND METHODS: We compared 241 ERCP performed from January 2014 to February 2015 with intravenous gabexate mesylate (Group A), with the 387 ERCP performed from March 2015 to December 2016 with rectal indomethacin (Group B) as prophylaxis for AP post-ERCP. RESULTS: There were 8 (3.31%) AP post-ERCP in Group A vs. 4 (1.03%) in Group B. CONCLUSIONS: Rectal indomethacin shows a better statistically significant performance than intravenous gabexate mesylate in the prophylaxis of AP post-ERCP, besides being cheaper.

Pitiriasis rosada: a propósito de un caso / Pityriasis rosea: Report of a case

Comunicamos el caso de una paciente femenina de 23 años de edad, natural y procedente de la localidad, quien consulta el 30 de Noviembre de 2016 al Centro Integral de Especialidades "Los Grillitos", CORPOSALUD, Municipio Mario Briceño Iragorry, por presentar lesiones puntiformes no pruriginosas en tronco, cuya aparición fue posterior al cuadro viral leve, motivo por el que acude al médico quien le indica antihistamínicos orales y glucocorticoides tópicos no fluorados. Con posterioridad a la primera consulta médica, se evidencian lesiones ovales rosadas con relieve no pruriginoso, diseminado en tronco. Se continúa tratamiento y se indica administrar una ampolla de betametasona intramuscular. Acude nuevamente a evaluación médica y se evidencian lesiones ovales menos eritematosas, descamativas en el límite del borde libre; en general se encuentran involucionadas, observándose actualmente mejoría clínica del cuadro.

We communicate a 23-year-old female patient, natural and from the locality, who on November 30, 2016, visits the Integral Center of Specialties "Los Grillitos", CORPOSALUD, Municipality Mario Briceño Iragorry, for presenting non-pruriginous punctate lesions on the trunk, which appeared after a mild viral picture, reason why she goes to the doctor who indicates oral antihistamines and non-fluorinated topical glucocorticoids. Subsequent medical evolution shows pink oval lesions with non-pruriginous relief, disseminated in the trunk. Treatment is continued and an intramuscular betamethasone ampoule is indicated. The patient returns to medical evaluation and there is evidence of oval lesions less erythematous, desquamative at the border of the free border; in general they are involuted, observing at the moment clinical improvement of the picture.

Factores de riesgo para alteraciones de la densidad mineral ósea en mujeres posmenopáusicas / Risk factors for alterations in bone mineral density in postmenopausal women

OBJETIVO: Determinar los factores de riesgo para presentar alteraciones de la densidad mineral ósea (DMO) en mujeres posmenopáusicas atendidas en la consulta de Menopausia y Climaterio de la Maternidad "Dr. Armando Castillo Plaza", de Maracaibo, Venezuela. MÉTODOS: Investigación descriptiva, con diseño no experimental y transeccional, donde se evaluó la DMO y los factores de riesgo para presentar osteoporosis en 60 mujeres posmenopáusicas. RESULTADOS: La medición de la DMO resultó en promedio de 957,45 ± 149,95 y 905,00 ± 151,25 gramos, con índices T de -0,52 ± 1,66 y -0,55 ± 2,67 en columna vertebral y cuello femoral, respectivamente. Se estableció una prevalencia de osteoporosis del 10% y 5%, y de osteopenia del 43,3% y 50% en columna vertebral y fémur, respectivamente. La menopausia quirúrgica (OR [95% CI] = 4,75 [1,58-14,25]; p=0,004), el consumo excesivo de café (OR [95% CI] = 3,20 [1,40-7,10 1]; p=0,000) o gaseosas (OR [95% CI] = 2,50 [1,18-5,60]; p=0,002), tabaquismo (OR [95% CI] = 1,70 [1,102,80]; p=0,013) y la ausencia de suplementación de calcio más vitamina D (OR [95% CI] = 1,70 [1,00-2,80]; p=0,019) resultaron ser factores significativamente asociados al diagnóstico de osteoporosis u osteopenia (p<0,05). CONCLUSIÓN: Las mujeres posmenopáusicas evaluadas presentan una alta prevalencia de alteraciones en la DMO, principalmente osteopenia, y factores de riesgo para presentar Osteoporosis.

AIM: To determine risk factors for presenting alterations in bone mineral density (BMD) in postmenopausal women attending the consultation of Menopause and Menopause Maternity "Dr. Armando Castillo Plaza", Maracaibo, Venezuela. METHODS: A descriptive research with non-experimental and transactional design where was evaluated BMD and risk factors for developing osteoporosis in 60 postmenopausal women. RESULTS: The BMD measurement was averaged in 957.45 ± 149.95 and 905.00 ± 151.25 grams; with T indexes of -0.52 ± 1.66 and -0.55 ± 2.67 in spine and femoral neck, respectively. The prevalence of osteoporosis was 10% and 5%, while osteopenia was 43.3% and 50% in spine and femur, respectively. Surgical menopause (OR [95% CI] = 4.75 [1.58 to 14.25]; p=0.004); excessive coffee consumption (OR [95% CI] = 3.20 [1,40- 7.10 1]; p=0.000) or gaseous beverages (OR [95% CI] = 2.50 [1.18 to 5.60]; p=0.002); smoking (OR [95% CI] = 1.70 [1.10 to 2.80]; p=0.013) and the absence of supplemental calcium plus vitamin D (OR [95% CI] = 1.70 [1.00 to 2.80]; p=0.019) were be factors significantly associated with the diagnosis of osteoporosis or osteopenia (p<0.05). CONCLUSION: The evaluated postmenopausal women have a high prevalence of abnormal BMD, especially osteopenia, and risk factors for developing osteoporosis.