Is iron overload associated with worse outcomes in patients with chronic liver disease undergoing liver transplantation?

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Efficacy and safety of self-expanding metal stents in patients with inoperable esophageal cancer: a real-life study.

Background: Dysphagia is the most frequent symptom in patients diagnosed with esophageal cancer. Self-expanding metal stents (SEMS) are the current palliative treatment of choice for dysphagia in patients with non-curable esophageal cancer. This study aimed to evaluate the efficacy and adverse events (AEs) of different types of SEMS for palliation of dysphagia. Methods: We performed a retrospective cohort study of patients with advanced esophageal cancer and SEMS placement for dysphagia palliation in a tertiary care center. The primary outcome was the clinical success defined as an improvement in dysphagia (reduction of at least 2 points in the Mellow-Pinkas scoring system for dysphagia) after SEMS placement. Results: Between January 1999 and May 2020, 295 patients with esophageal cancer were identified. Among them, 75 had a SEMS placement for dysphagia palliation. The mean age of the patients was 61.3 years (standard deviation: 13.4), 69 patients (92%) were men, and the mean Mellow-Pinkas scoring for dysphagia pre- and post-SEMS placement were 3.1 and 1.4 (change from baseline -1.7), respectively. Technical success and clinical success were achieved in 98.6% and 58.9%, respectively. AEs were identified in 35/75 patients (46.7%), and SEMS migration was the most frequent AE in 22/75 patients (29.3%). There were no significant differences in improvement in dysphagia (p = 0.054), weight changes (p = 0.78), and AE (p = 0.73) among fully covered SEMS (fc-SEMS) and partially covered SEMS (pc-SEMS). The median follow-up was 89 days (interquartile range: 29-221). Conclusion: SEMS placement was associated with a rapid improvement in dysphagia, high technical success, and a modest improvement in dysphagia with no major AE among fc-SEMS and pc-SEMS.

Test sensitivity in a prospective cancer screening program: A critique of a common proxy measure.

The true sensitivity of a cancer screening test, defined as the frequency with which the test returns a positive result if the cancer is present, is a key indicator of diagnostic performance. Given the challenges of directly assessing test sensitivity in a prospective screening program, proxy measures for true sensitivity are frequently reported. We call one such proxy empirical sensitivity, as it is given by the observed ratio of screen-detected cancers to the sum of screen-detected and interval cancers. In the setting of the canonical three-state Markov model for progression from preclinical onset to clinical diagnosis, we formulate a mathematical relationship for how empirical sensitivity varies with the screening interval and the mean preclinical sojourn time and identify conditions under which empirical sensitivity exceeds or falls short of true sensitivity. In particular, when the inter-screening interval is short relative to the mean sojourn time, empirical sensitivity tends to exceed true sensitivity, unless true sensitivity is high. The Breast Cancer Surveillance Consortium (BCSC) has reported an estimate of 0.87 for the empirical sensitivity of digital mammography. We show that this corresponds to a true sensitivity of 0.82 under a mean sojourn time of 3.6 years estimated based on breast cancer screening trials. However, the BCSC estimate of empirical sensitivity corresponds to even lower true sensitivity under more contemporary, longer estimates of mean sojourn time. Consistently applied nomenclature that distinguishes empirical sensitivity from true sensitivity is needed to ensure that published estimates of sensitivity from prospective screening studies are properly interpreted.

HIV-positive patients presenting with peripheral blood cytopenias: is bone marrow assessment a priority?

ABSTRACT Introduction: Hematologic abnormalities are frequent among persons living with HIV (PLWH). The bone marrow aspirate (BMA) and biopsy (BMB) are commonly performed in the diagnostic approach of patients with unexplained cytopenias. Changes in antiretrovirals, supportive therapy and increased life expectancy have modified the distribution and etiology of cytopenias, questioning their use. Our aim was to analyze the diagnostic yield of BMA, BMB and marrow cultures for the evaluation of cytopenias in PLWH. Methods: This was a retrospective cohort of ≥ 18-year-old PLWH undergoing bone marrow assessment (MA) for the evaluation of cytopenias between January 2002 and December 2015. Results: A total of 236 cytopenic events were analyzed, 47.9% being PLWH who had a longstanding diagnosis (≥ 1 year). Adherence to antiretrovirals was 63.5%. Anemia was seen in 91.9% and pancytopenia in 39%. Common presentations included fever (52.1%), weight loss (42.8%) and adenopathies (28.8%). Median days from detection to MA was 5 (0 - 63 days). Most common etiologies were non-HIV infectious diseases (31.4%) and benign/malignant hematologic diseases (26.3%). The diagnostic yield was 16.1% for BMA, 20.3% for BMB, 30.5% for both and 35.6% when cultures were added. Patients most likely to have conclusive MA were those with moderate/severe thrombocytopenia (p = 0.007). Fever, splenomegaly, and low CD4+ counts were associated with infectious etiologies, while hematologic diagnoses were related to the presence of adenopathies. Conclusion: As a minimally invasive intervention, the MA has a high yield for identifying the etiology of cytopenic events in PLWH, being conclusive in one in three patients. Early performance could lead to prompt diagnosis and timely therapy initiation.

Factors Associated with Development of Acute Kidney Injury After Liver Transplantation.

BACKGROUND: Early post-liver transplant (LT) acute kidney injury (AKI) has been associated with worse short-term and long-term outcomes, but the incidence and risk factors in our population are unknown. METHODS: We designed a prospective, singlecenter, longitudinal cohort study to determine the incidence of AKI during the immediate postoperative period of LT, and to identify the risk factors associated with AKI after LT. Pre-operative and intraoperative variables were analyzed to determine if there was any correlation with the development of post-operative AKI. RESULTS: Eighty-six patients were included in the final analysis; from them, 45 (52%) developed AKI in the following 30 days after LT. The presence of hepatic encephalopathy prior to LT was the factor most strongly associated with the development of AKI (Relative Risk 3.67, 95% Confidence Interval 1.08-8.95). Other factors associated with AKI development were male gender and a higher serum lactate during surgery. CONCLUSION: AKI was a frequent complication that significantly worsened the prognosis of LT recipients and was associated with an increased 30-day mortality rate. The presence of hepatic encephalopathy strongly predicted the development of severe AKI.

HIV-positive patients presenting with peripheral blood cytopenias: is bone marrow assessment a priority?

INTRODUCTION: Hematologic abnormalities are frequent among persons living with HIV (PLWH). The bone marrow aspirate (BMA) and biopsy (BMB) are commonly performed in the diagnostic approach of patients with unexplained cytopenias. Changes in antiretrovirals, supportive therapy and increased life expectancy have modified the distribution and etiology of cytopenias, questioning their use. Our aim was to analyze the diagnostic yield of BMA, BMB and marrow cultures for the evaluation of cytopenias in PLWH. METHODS: This was a retrospective cohort of ≥ 18-year-old PLWH undergoing bone marrow assessment (MA) for the evaluation of cytopenias between January 2002 and December 2015. RESULTS: A total of 236 cytopenic events were analyzed, 47.9% being PLWH who had a longstanding diagnosis (≥ 1 year). Adherence to antiretrovirals was 63.5%. Anemia was seen in 91.9% and pancytopenia in 39%. Common presentations included fever (52.1%), weight loss (42.8%) and adenopathies (28.8%). Median days from detection to MA was 5 (0 - 63 days). Most common etiologies were non-HIV infectious diseases (31.4%) and benign/malignant hematologic diseases (26.3%). The diagnostic yield was 16.1% for BMA, 20.3% for BMB, 30.5% for both and 35.6% when cultures were added. Patients most likely to have conclusive MA were those with moderate/severe thrombocytopenia (p = 0.007). Fever, splenomegaly, and low CD4+ counts were associated with infectious etiologies, while hematologic diagnoses were related to the presence of adenopathies. CONCLUSION: As a minimally invasive intervention, the MA has a high yield for identifying the etiology of cytopenic events in PLWH, being conclusive in one in three patients. Early performance could lead to prompt diagnosis and timely therapy initiation.

Cirrhosis etiology trends in developing countries: Transition from infectious to metabolic conditions. Report from a multicentric cohort in central Mexico.

Background: Cirrhosis is a public health threat associated with high mortality. Alcoholic Liver Disease (ALD) is the leading cause in Latin America and Metabolic Associated Fatty Liver Disease (MAFLD) in western countries. In Mexico, ALD and chronic Hepatitis C Virus infection (HCV) were the most frequent aetiologies during the past decades. We aimed to describe the trends in the aetiologies of cirrhosis in a middle-income country. Methods: We performed a retrospective cohort study including patients diagnosed with cirrhosis between 2000 and 2019 from six different tertiary care hospitals in central Mexico. We collected information regarding cirrhosis etiology, year of diagnosis, hepatocellular carcinoma development, liver transplantation, and death. We illustrated the change in the tendencies of cirrhosis aetiologies by displaying the proportional incidence of each etiology over time stratified by age and gender, and we compared these proportions over time using chi square tests. Findings: Overall, 4,584 patients were included. In 2019, MAFLD was the most frequent cirrhosis etiology (30%), followed by ALD (24%) and HCV (23%). During the study period, MAFLD became the leading etiology, ALD remained second, and HCV passed from first to fourth. When analysed by gender, ALD was the leading etiology for men and MAFLD for women. The annual incidence of HCC was 3·84 cases/100 persons-year, the median survival after diagnosis was 12·1 years, and seven percent underwent LT. Interpretation: Increased alcohol consumption and the obesity epidemic have caused a transition in the aetiologies of cirrhosis in Mexico. Public health policies must be tailored accordingly to mitigate the burden of alcohol and metabolic conditions in developing countries. Funding: None.

Causes of erythrocytosis and its impact as a risk factor for thrombosis according to etiology: experience in a referral center in Mexico City.

BACKGROUND: Thrombotic events are well documented in primary erythrocytosis, but it is uncertain if secondary etiologies increase the risk of thrombosis. This study aimed to determine the causes of erythrocytosis and to identify its impact as a risk factor for thrombosis. METHODS: Data were obtained from patients with erythrocytosis between 2000 and 2017 at a referral hospital in Mexico City. Erythrocytosis was defined according to the 2016 WHO classification. Time to thrombosis, major bleeding, or death were compared among groups of patients defined by the etiology of erythrocytosis using a Cox regression model, adjusting for cardiovascular risk factors. RESULTS: In total, 330 patients with erythrocytosis were studied. The main etiologies of erythrocytosis were obstructive sleep apnea (OSA) in 29%, polycythemia vera (PV) in 18%, and chronic lung disease (CLD) in 9.4% of the patients. The incidence rate of thrombosis was significantly higher in patients with PV and CLD than that in patients with OSA (incidence rates of 4.51 and 6.24 vs. 1.46 cases per 100 person-years, P=0.009), as well as the mortality rate (mortality rates of 2.72 and 2.43 vs. 0.17 cases per 100 person-years, P =0.003). CONCLUSION: The risk of thrombosis in CLD with erythrocytosis was comparable to that in patients with PV. Further larger-scale studies are needed to confirm these findings and evaluate the benefits of preventive management of COPD with erythrocytosis similar to PV.

Do we need skin toxicity? Association of immune checkpoint inhibitor and tyrosine kinase inhibitor-related cutaneous adverse events with outcomes in metastatic renal cell carcinoma.

INTRODUCTION: Skin toxicity is a common, expected side effect of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) used for metastatic renal cell carcinoma (mRCC). We evaluated the association between skin toxicity and clinical efficacy outcomes of these agents in mRCC patients. METHODS AND MATERIALS: Data were obtained from patients with mRCC treated with TKIs and/or ICIs from 2016-2019 at a referral hospital in Mexico City. Clinical outcomes were compared among patients who developed treatment-related cutaneous adverse events (AEs) and those without skin toxicity. RESULTS: Thirty-five patients with mRCC were identified who were treated with sunitinib (51.4%), nivolumab plus cabozantinib (28.6%), nivolumab monotherapy (17.1%), or ipilimumab plus nivolumab plus cabozantinib (2.9%). Any grade skin toxicity was seen in 65.7% of patients. With a median follow-up of 14 months, radiological responses were as follows: 48.6% stable disease, 25.7% partial response, and 2.8% complete response. Compared to subjects without skin toxicity, patients who developed cutaneous AEs had higher disease control rate 91.3% vs. 50.0% (P = 0.019) and superior 12-month overall survival rate 91% vs. 67% (P = 0.01), respectively. There was a trend toward improved median progression-free survival (16 months vs. 5 months, P = 0.13). Grade 1-2 cutaneous toxicity was found to be predictive for disease control, with HR 2.72 (95% CI 1.1-6.71, P = 0.030), and all grade cutaneous toxicity was prognostic of overall survival, with HR 0.18 (95% CI 0.04-0.91, P = 0.039). CONCLUSION: Cutaneous AEs are associated with improved overall survival and response in patients with mRCC treated with immunotherapy and/or TKIs.

18f-Fluorodeoxyglucose Positron Emission Tomography Versus Bone Marrow Biopsy for the Evaluation of Bone Marrow Infiltration in Newly Diagnosed Lymphoma Patients

ABSTRACT Background: Bone marrow evaluation (BME) is crucial for establishing an accurate staging and prognosis in lymphoma patients. Objective: The objective of the study was to study the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) against bone marrow biopsy (BMB) for BME. Methods: Five hundred patient files of newly diagnosed lymphoma patients treated at an academic medical center were reviewed for BME at diagnosis by BMB and FDG PET-CT. Diagnostic performance of FDG PET-CT for detecting bone marrow infiltration (BMI) was assessed, as well as clinical predictors for positive BMB and positive FDG PET-CT. Results: BMB was positive in 16.3% of all patients, and 28.7% had a positive FDG PET-CT for BMI. Overall, the sensitivity of FDG PET-CT was 74.1% and specificity 80.1%. As for predictors for BMB and FDG PET-CT positivity, B symptoms and thrombocytopenia were independent factors for BMI. Seventy-four patients had discordant results between BMB and FDG PET-CT, non-Hodgkin lymphoma (NHL) having the most significant discordance. This discrepancy did not affect treatment. Conclusions: FDG PET-CT shows excellent performance for the detection of BMI in Hodgkin lymphoma. For diffuse large B-cell lymphoma, we recommend performing BMB and FDG PET-CT as complementary tests. In all other NHL, a unilateral BMB is mandatory at diagnosis.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico.

BACKGROUND: The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. METHODOLOGY/PRINCIPAL FINDINGS: We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78-30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4-76.2) / 96.2% (95% CI, 93.2-98.0) for IAHE, 91.3% (95% CI, 84.2-96.0) / 90.9% (95% CI, 87.0-94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0-95.3) / 92.3% (95% CI, 88.6-95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3-72.5)/ 89.5% (95%CI, 86.0-93.0), 65.9% (95%CI, 56.0-75.8)/ 89.0% (95%CI, 85.2-92.9), 62.1% (95%CI, 44.4-79.7)/ 82.6% (95%CI, 71.7-93.6) and 34.9% (95%CI, 24.8-46.2)/ 67.3% (95%CI, 60.6-73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9-74.7)/ 58.8% (95%CI, 53.2-64.5), 70.8% (95%CI, 61.3-80.2)/ 52.9% (95%CI, 46.8-59.1), 71.4% (95%CI, 54.7-88.2)/ 40.4% (95%CI, 26.4-54.5) and 18.1% (95%CI, 10.5-28.1)/ 90.4% (95%CI, 85.5-94.0), respectively. CONCLUSIONS/SIGNIFICANCE: The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

18f-Fluorodeoxyglucose Positron Emission Tomography Versus Bone Marrow Biopsy for the Evaluation of Bone Marrow Infiltration in Newly Diagnosed Lymphoma Patients.

BACKGROUND: Bone marrow evaluation (BME) is crucial for establishing an accurate staging and prognosis in lymphoma patients. OBJECTIVE: The objective of the study was to study the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) against bone marrow biopsy (BMB) for BME. METHODS: Five hundred patient files of newly diagnosed lymphoma patients treated at an academic medical center were reviewed for BME at diagnosis by BMB and FDG PET-CT. Diagnostic performance of FDG PET-CT for detecting bone marrow infiltration (BMI)was assessed, as well as clinical predictors for positive BMB and positive FDG PET-CT. RESULTS: BMB was positive in 16.3% of all patients, and 28.7% had a positive FDG PET-CT for BMI. Overall, the sensitivity of FDG PET-CT was 74.1% and specificity 80.1%. As for predictors for BMB and FDG PET-CT positivity, B symptoms and thrombocytopenia were independent factors for BMI. Seventy-four patients had discordant results between BMB and FDG PET-CT, non-Hodgkin lymphoma (NHL) having the most significant discordance. This discrepancy did not affect treatment. CONCLUSIONS: FDG PET-CT shows excellent performance for the detection of BMI in Hodgkin lymphoma. For diffuse large B-cell lymphoma, we recommend performing BMB and FDG PET-CT as complementary tests. In all other NHL, a unilateral BMB is mandatory at diagnosis.

Clinical and epidemiological characteristics of patients diagnosed with covid-19 in a tertiary care center in Mexico City: a prospective cohort study

ABSTRACT Background: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. Objective: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). Methods: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. Results: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. Conclusions: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.