Thrombosis in breast cancer patients on cyclin-dependent kinase inhibitors: Survival impact and predictive factors - A study by the cancer and thrombosis group of the spanish society of medical oncology (SEOM).

Thrombosis may be included in the profile of side effects associated with CDK4/6 inhibitors. Its significance might be greater than reported in randomized clinical trials. To investigate this, a retrospective, multicenter study was conducted. The primary objective was to calculate the incidence of thrombosis associated with CDK4/6 inhibitors. Secondary objectives included examining the impact of thrombosis on survival and identifying predictor variables for the development of venous thromboembolism (VTE) or arterial thrombosis (AT). A total of 986 patients were recruited. The incidence of VTE/AT associated with CDK4/6 inhibitor treatment during the follow-up period was 5.48 %. Survival analysis did not indicate that the development of VTE/AT during CDK4/6 inhibitor treatment significantly impacted patient survival (p = 0.133). In our analysis, two variables were found to be statistically significant (p < 0.05) as predictors of VTE/AT in breast cancer patients receiving CDK4/6 inhibitor therapy. These variables were the presence of central nervous system (CNS) metastasis with an odds ratio (OR) of 3.68 (95 % CI 1.18 - 11.49) and the use of abemaciclib with an OR of 2.3 (95 % CI 1.16 - 4.57).

Prediction of mortality in acute pulmonary embolism in cancer-associated thrombosis (MAUPE-C): derivation and validation of a multivariable model.

Optimal risk stratification of patients with cancer and pulmonary embolism (PE) remains unclear. We constructed a clinical prediction rule (CPR) named 'MAUPE-C' to identify patients with low 30 days mortality. The study retrospectively developed and internally validated a CPR for 30 days mortality in a cohort of patients with cancer and PE (both suspected and unsuspected). Candidate variables were chosen based on the EPIPHANY study, which categorized patients into 3 groups based on symptoms, signs, suspicion and patient setting at PE diagnosis. The performance of 'MAUPE-C' was compared to RIETE and sPESI scores. Univariate analysis confirmed that the presence of symptoms, signs, suspicion and inpatient diagnosis were associated with 30 days mortality. Multivariable logistic regression analysis led to the exclusion of symptoms as predictive variable. 'MAUPE-C' was developed by assigning weights to risk factors related to the ß coefficient, yielding a score range of 0 to 4.5. After receiver operating characteristic (ROC) curve analysis, a cutoff point was established at ≤ 1. Prognostic accuracy was good with an area under the curve (AUC) of 0.77 (95% CI 0.71-0.82), outperforming RIETE and sPESI scores in this cohort (AUC of 0.64 [95% CI 0.57-0.71] and 0.57 [95% CI 0.49-0.65], respectively). Forty-five per cent of patients were classified as low risk and experienced a 2.79% 30 days mortality. MAUPE-C has good prognostic accuracy in identifying patients at low risk of 30 days mortality. This CPR could help physicians select patients for early discharge.

Bacteremia in Patients with Solid Organ Cancer: Insights into Epidemiology and Antibiotic Consumption.

Epidemiology and risk factors associated to bacterial resistance in solid organ cancer (SOC) patients has been barely described. This retrospective monocentric study analyzed clinical variables in SOC patients who developed bacteremia between 1 January 2019 and 31 December 2022. We described rates of bacterial resistance in Gram negative bacteria (80.6%): E. coli-ESBL, K. pneumoniae-ESBL, Carbapenem-Resistant K. pneumoniae and Meropenem-Resistant P. aeruginosa, as well as antibiotic consumption, and compared these rates between the medical and oncology wards. In total, we included 314 bacteremias from 253 patients. SOC patients are frequently prescribed antibiotics (40.8%), mainly fluoroquinolones. Nosocomial bacteremia accounted for 18.2% of the cases and only 14.3% of patients were neutropenic. Hepatobiliary tract was the most frequent tumor (31.5%) and source of bacteremia (38.5%). Resistant bacteria showed a decreased rate of resistance during the years studied in the oncology ward. Both K-ESBL and K-CBP resistance rates decreased (from 45.8% to 20.0%, and from 29.2% to 20.0%, respectively), as well as MRPA, which varied from a resistance rate of 28% to 16.7%. The presence of a urinary catheter (p < 0.001) and previous antibiotic prescription (p = 0.002) were risk factors for bacterial resistance. Identifying either of these risk factors could help in guiding antibiotic prescription for SOC patients.

Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study.

BACKGROUND: Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival. METHODS: This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors. FINDINGS: From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2·5, 95% CI 1·1-6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4-17·8 and HR 6·6, 1·4-31·0, respectively). INTERPRETATION: Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment. FUNDING: The Instituto de Salud Carlos III and the European Union.

Cancer-associated splanchnic vein thrombosis: Clinical features upon diagnosis and short-term outcomes.

INTRODUCTION: The incidence of splanchnic vein thrombosis (SVT) in cancer patients has increased in recent years and its real clinical significance and management can be challenging. This study aimed to describe the clinical presentation and short-term outcomes of patients with cancer-associated SVT. MATERIAL AND METHODS: This was a retrospective observational study of consecutive patients with cancer-associated SVT diagnosed during the period 2015-2020. The primary objective was to describe the clinical presentation of SVT. Patients were clinically classified into two groups based on the presence of symptoms on SVT diagnosis. The main outcomes were overall and SVT-related mortality, major and non-major bleeding rates, and the thrombosis recurrence rate in the first 30 days of follow-up. RESULTS: This study enrolled 203 patients. Intra-abdominal tumors (76 %) and metastatic disease (68 %) predominated. A total of 79 (39 %) patients without symptoms were diagnosed with SVT during a scheduled radiological test and were classified as "asymptomatic", while 124 (61 %) patients presented some potential SVT symptoms and were considered as "symptomatic". Although the 30-day outcomes showed no significant differences between the two groups, mortality in the asymptomatic group was slightly lower compared to the symptomatic group (3 % vs. 10 %, p = 0.085). CONCLUSIONS: Almost 40 % of cases of cancer-associated SVT are asymptomatic. There were no significant differences in short-term outcomes between the symptomatic and asymptomatic patients. More studies are required to better define long-term management and outcomes in these patients.

Multidisciplinary management in chronic myeloid leukemia improves cardiovascular risk measured by SCORE.

Introduction: Cardiovascular events are one of the main long-term complications in patients with chronic myeloid leukemia (CML) receiving treatment with tyrosine kinase inhibitors (TKIs). The proper choice of TKI and the adequate management of risk factors may reduce cardiovascular comorbidity in this population. Methods: This study evaluated the cardiovascular risk of a cohort of patients with CML at diagnosis and after follow-up in a specialized cardiovascular risk consultation. In order to do this, we performed data analysis from 35 patients who received TKIs and were referred to the aforementioned consultation between 2015 and 2018 at our center. Cardiovascular risk factors were analyzed separately, as well as integrated into the cardiovascular SCORE, both at diagnosis and at the last visit to the specialized consultation. Results: At the time of diagnosis, 60% had some type of risk factor, 20% had a high or very high risk SCORE, 40% had an intermediate risk, and 40% belonged to the low risk category. During follow-up, the main cardiovascular adverse event observed was hypertension (diagnosed in 8 patients, 23%). 66% of patients quit smoking, achieving control of blood pressure in 95%, diabetes in 50%, weight in 76%, and dyslipidemia in 92%. 5.7% of patients suffered a thrombotic event and a significant percentage of patients showed a reduction in their SCORE. Conclusion: Our study shows the benefit of controlling cardiovascular risk factors through follow-up in a specialized consultation for patients with CML treated with TKI.

Saddle Pulmonary Embolism in Patients with Cancer in the Era of Incidental Events: Clinical Findings and Outcomes in a Single Centre Cohort.

Background There is scarce information regarding the prevalence and clinical impact of saddle pulmonary embolism (PE) in patients with cancer. Objectives This study aimed to assess the prevalence, clinical findings, and short-term outcomes of patients with cancer-related saddle PE including acute symptomatic and unsuspected events. Patients/Methods Consecutive patients with cancer-related PE (March 1, 2006-October 31, 2014) were retrospectively reviewed by a chest radiologist to assess PE burden and signs of right ventricular (RV) overload. The clinical outcomes within 30 days were evaluated according to saddle versus nonsaddle PE. Results Thirty-six (12%) out of 289 patients with newly diagnosed cancer-related PE presented with saddle PE. Saddle PE was found in 21 cases (58%) with acute symptomatic PE and the remaining 15 cases (42%) were found as unsuspected findings. Patients with saddle PE had more frequently experienced a previous thrombotic event (31 vs. 13%; p =0.008), and it occurred more frequently as an acute symptomatic event (58 vs. 39%; p =0.025) compared with those with nonsaddle PE. Signs of RV overload including RV/left ventricle ratio ≥1 (22 vs. 4%; p <0.001) and interventricular septum displacement (53 vs. 20%; p <0.001) were also more common in patients with saddle PE compared with nonsaddle PE. Overall, PE-related mortality, venous thromboembolism recurrence, and major bleeding within 30 days were found to be similar according to saddle versus nonsaddle PE. Conclusion Saddle PE is not uncommon in patients with cancer-related PE including in those with unsuspected PE. Similar 30-day outcomes were found according to saddle versus nonsaddle PE in our cohort.

Saddle Pulmonary Embolism in Patients with Cancer in the Era of Incidental Events: Clinical Findings and Outcomes in a Single Centre Cohort.

Background There is scarce information regarding the prevalence and clinical impact of saddle pulmonary embolism (PE) in patients with cancer. Objectives This study aimed to assess the prevalence, clinical findings, and short-term outcomes of patients with cancer-related saddle PE including acute symptomatic and unsuspected events. Patients/Methods Consecutive patients with cancer-related PE (March 1, 2006-October 31, 2014) were retrospectively reviewed by a chest radiologist to assess PE burden and signs of right ventricular (RV) overload. The clinical outcomes within 30 days were evaluated according to saddle versus nonsaddle PE. Results Thirty-six (12%) out of 289 patients with newly diagnosed cancer-related PE presented with saddle PE. Saddle PE was found in 21 cases (58%) with acute symptomatic PE and the remaining 15 cases (42%) were found as unsuspected findings. Patients with saddle PE had more frequently experienced a previous thrombotic event (31 vs. 13%; p = 0.008), and it occurred more frequently as an acute symptomatic event (58 vs. 39%; p = 0.025) compared with those with nonsaddle PE. Signs of RV overload including RV/left ventricle ratio ≥1 (22 vs. 4%; p < 0.001) and interventricular septum displacement (53 vs. 20%; p < 0.001) were also more common in patients with saddle PE compared with nonsaddle PE. Overall, PE-related mortality, venous thromboembolism recurrence, and major bleeding within 30 days were found to be similar according to saddle versus nonsaddle PE. Conclusion Saddle PE is not uncommon in patients with cancer-related PE including in those with unsuspected PE. Similar 30-day outcomes were found according to saddle versus nonsaddle PE in our cohort.

Clinical Differences and Outcomes of COVID-19 Associated Pulmonary Thromboembolism in Comparison with Non-COVID-19 Pulmonary Thromboembolism.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been reported to increase the risk of pulmonary thromboembolism (PTE). The aim of this study is to elucidate whether Coronavirus disease COVID-19-associated PTE has a different clinical expression than non-COVID-19 PTE due to a different pathophysiology. (2) Methods: retrospective study of PTE episodes conducted at our hospital between January 2019 and December 2020, comparing the group of COVID-19-associated PTE patients with a control group of non-COVID-19 PTE patients. (3) Results: A total of 229 patients with PTE were registered, 79 of whom had COVID-19. Cancer (15.2% vs. 39.3%; p < 0.001), previous surgery (0% vs. 8%; p = 0.01), previous VTE (2.5% vs. 15.3%; p = 0.003), signs and/or symptoms of deep venous thrombosis (DVT) (7.6% vs. 22.7%; p = 0.004) and syncope (1.3% vs. 8.1%; p = 0.035) were less frequent in the COVID-19 group. Central thrombosis was more frequent in the control group (35.3% vs. 13.9%; p = 0.001). No VTE recurrent episodes were observed in the COVID-19 group, whereas four (2.7%) episodes were recorded for the control group. One-month bleeding rate was higher in the COVID-19 group (10.1% vs. 1.3%; p = 0.004). (4) Conclusion: COVID-19-associated PTE has clinical characteristics that differ from those of PTE without COVID-19, including inferior severity and a lower rate of VTE recurrence. Physicians should be aware of the high risk of bleeding in the first month of COVID-19-associated PTE.

Cancer Histology and Natural History of Patients with Lung Cancer and Venous Thromboembolism.

Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45-214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76-18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09-0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76-1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite.

Higher mortality of hospitalized haematologic patients with COVID-19 compared to non-haematologic is driven by thrombotic complications and development of ARDS: An age-matched cohorts study.

BACKGROUND AND OBJECTIVES: The characteristics of COVID-19 in haematologic patients compared to non-haematologic patients have seldom been analyzed. Our aim was to analyze whether there are differences in clinical characteristics and outcome of haematologic patients with COVID-19 as compared to non-haematologic. PATIENTS AND METHODS: Retrospective cohort study in 2 University hospitals of patients admitted with laboratory-confirmed COVID-19 included in the SEMICOVID19 database. The cohort with underlying haematologic disease was compared to a cohort of age and date-of-COVID-19-matched controls without haematologic disease (1:2). RESULTS: 71 cases and 142 controls were included from March-May 2020.Twenty (28.1%) had received recent chemotherapy. Twelve (16.9%) were stem cell transplant recipients (SCT). Eleven (15.5%) were neutropenic concurrently with COVID-19 diagnosis.Haematologic patients presented ARDS (58.5 vs 20.7%, p = 0.0001), thrombotic complications (15.7 vs 2.1%, p = 0.002), DIC (5.7 vs 0.0%, p = 0.011), heart failure (14.3 vs 4.9%, p = 0.029) and required ICU admission (15.5 vs 2.8%, p = 0.001), MV (14.1% vs 2.1%, p 0.001), steroid (64.8 vs 33.1%, p = 0.0001), tocilizumab (33.8 vs 8.5%, p = 0.0001) or anakinra treatment (9.9% vs 0%, p = 0.0001) more often. In-hospital mortality was significantly higher (38.0% vs 18.3%, p = 0.002). CONCLUSIONS: Our results suggest COVID-19 has worse outcomes in haematologic patients than in non-haematologic, independently of age, and that the development of ARDS and thrombotic complications drive the higher in-hospital mortality.

Incidence of venous thromboembolism in patients with non-hematological cancer admitted for COVID-19 at a third-level hospital in Madrid.

An increased risk of venous thromboembolism (VTE) in hospitalized patients with COVID-19 has been reported. We aimed to describe the incidence rate of VTE on patients with non-hematological cancer who required hospitalization due to COVID-19 at our center. In this prospective study, non-hematological cancer patients hospitalized for confirmed COVID-19 at our institution from 1st March to 30th April 2020, were evaluated daily for VTE complications during their hospital stay, and after discharge until 30th June 2020. Furthermore, Doppler ultrasound of lower limbs was routinely performed in asymptomatic patients based on D-dimer levels and current active cancer therapy. The primary outcome of this study was the cumulative incidence of VTE. Secondary outcomes were the cumulative incidence of bleeding and mortality. A total of 58 hospitalized non-hematological cancer patients and confirmed COVID-19 were identified. Median follow-up since initial symptoms of COVID-19 was 91 days (IQR 19-104). Pulmonary embolism was diagnosed in three (5%) patients. Symptomatic catheter-related deep vein thrombosis (DVT) was observed in one patient. Doppler ultrasound of lower limbs was done in 11 asymptomatic patients, showing distal DVT in two of them (18%). The cumulative incidence of VTE on day 14 after admission was 10%, without new VTE events after hospital discharge and up to 90 days follow-up. No bleeding complication was observed. Seventeen patients (29%) died in the first 14 days after COVID-19 diagnosis. Four patients died after discharge due to malignancy progression. The cumulative incidence of VTE in non-hematological cancer patients under active treatment was 10% at day 14 after admission, with no further new events in the following 12 weeks.

SARS-CoV-2 infection in cancer patients undergoing active treatment: analysis of clinical features and predictive factors for severe respiratory failure and death.

AIM: Previous studies have suggested a more frequent and severe course of novel coronavirus SARS-CoV-2 infection in cancer patients undergoing active oncologic treatment. Our aim was to describe the characteristics of the disease in this population and to determine predictive factors for poor outcome in terms of severe respiratory distress (acute respiratory distress syndrome [ARDS]) or death. PATIENTS AND METHODS: Patients consecutively admitted for SARS-CoV-2 infection were prospectively collected, and retrospective statistical analysis was performed. Univariate and multivariate analyses were performed to assess potential factors for poor outcomes defined as ARDS or death. RESULTS: Sixty-three patients were analysed, and 34 of them developed respiratory failure (70% as ARDS). Lymphocytes/mm3 (412 versus 686; p = 0.001), serum albumin (2.84 versus 3.1); lactate dehydrogenase (LDH) (670 versus 359; p < 0.001) and C-reactive protein (CRP) levels (25.8 versus 9.9; p < 0.001) discriminate those that developed respiratory failure. Mortality rate was 25%, significantly higher among ARDS, neutropenic patients (p = 0.01) and in those with bilateral infiltrates (44% versus 0%; p < 0.001). Multivariate logistic analyses model confirmed the predictive value of severe neutropenia (odds ratio [OR] 16.54; 95% confidence interval [CI] 1.43-190.9, p 0.025), bilateral infiltrates (OR 32.83, CI 95% 3.51-307, p 0.002) and tumour lung involvement (OR 4.34, CI 95% 1.2-14.95, p 0.02). CONCLUSION: Cancer patients under active treatment admitted for SARS-CoV-2 infection have worse outcomes in terms of mortality and respiratory failure rates compared with COVID-19 global population. Lymphopenia, LDH, CRP and albumin discriminate illness severity, whereas neutropenia, bilateral infiltrates and tumour pulmonary involvement are predictive of higher mortality.

An unsuspected complication with immune checkpoint blockade: a case report.

BACKGROUND: Immunotherapy treatment with immune-checkpoint blockade has become a new paradigm in cancer treatment. Despite its efficacy, it has also given rise to a new class of adverse events, immune-related adverse events, which may affect any organ, including the thyroid and the pituitary. CASE PRESENTATION: We present a case of a 77-year-old Caucasian man with metastatic renal cell carcinoma on immunotherapy treatment who was admitted to our hospital with a severe persistent headache of sudden onset. He had been on corticosteroid therapy for 10 days for suspected immune-related thyroiditis. The patient had tachycardia and mild diarrhea, and his thyroid function tests were compatible with subclinical hyperthyroidism with a suppressed thyroid-stimulating hormone level of 0.01 µIU/ml (0.4-4.5), a raised free T4 level of 2.17 ng/dl (0.7-1.9), and a free T3 level of 4.66 pg/ml (2.27-5). Computed tomography and magnetic resonance imaging revealed an enlargement of the pituitary gland compatible with macroadenoma. In the face of a probable immune-related hypophysitis, high-dose corticosteroid treatment was started. A posterior hormonal evaluation revealed secondary hypothyroidism with a suppressed thyroid-stimulating hormone level of 0.11 µIU/ml (0.4-4.5) and low thyroid hormones, a normal free T4 level of 1.02 ng/dl (0.7-1.9), and a low free T3 level of 1.53 pg/ml (2.27-5). These new findings suggested central hypothyroidism possibly due to pituitary apoplexy as a complication of the macroadenoma. Therefore, levothyroxine substitution was started along with the previously started corticosteroid therapy. The patient's headache and asthenia gradually resolved, and after a few days, he was released from the hospital with levothyroxine substitution and corticosteroid tapering. CONCLUSIONS: This case emphasizes the importance of the differential diagnosis when dealing with patients on immune checkpoint inhibitors because other non-immune-related events may present. Our patient was finally diagnosed with immune-related hyperthyroidism and a concurrent pituitary macroadenoma. This case also highlights the importance of a prompt start of corticosteroid therapy once immune-related adverse events such as hypophysitis are suspected, because otherwise the outcome would be fatal.

Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis.

OBJECTIVE: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model. PATIENTS AND METHODS: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017. RESULTS: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P<.001), mixed microbiological infections (P=.02), and more than 1 infection (P=.01) and glucocorticoid monotherapy (P=.02). According to univariate analyses, platelets of less than 100,000/mm3 (hazard ratio [HR], 3.39; 95% CI, 1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR, 1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95% CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98) and the immunosuppressive drug/intravenous immunoglobulin/biological therapies (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality. Multivariable Cox proportional hazards regression analysis identified 2 or more infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable independently associated with death. CONCLUSION: The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with more than 1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation, and therapeutic management.

Impact of functional status on 6-month mortality in elderly patients with acute venous thromboembolism: results from a prospective cohort.

Functional status linked to a poor outcome in a broad spectrum of medical disorders. Barthel Activities of Daily Life Index (BADLI) is one of the most extended tools to quantify functional dependence. Whether BADLI can help to predict outcomes in elderly patients with acute venous thromboembolism (VTE) is unknown. The current study aimed to ascertain the influence of BADLI on 6-month all-cause mortality in aged patients with VTE. This is a prospective observational study. We included consecutive patients older than 75-year-old with an acute VTE between April 2015 and April 2017. We analyzed several variables as mortality predictors, including BADLI-measured functional status. Afterward, we performed a multivariate analysis, using logistic regression, to identify all-cause mortality independent predictive factors. Two hundred and two subjects were included. Thirty-five (17%) patients died in the first 6 months. The leading cause of death was cancer (59%). After multivariable logistic regression, we identified BADLI and Charlson index as independent predictors for 6-months mortality [BADLI (every decrease of 10 points) OR 1.21 95% CI (1.03-1.42) and Charlson index OR 1.71 95% CI (1.21-2.43)]. Body mass index (BMI) values were inversely related to mortality [OR 0.85 95% CI (0.75-0.95)]. In conclusion, BADLI, BMI, and Charlson index scores are independent predictive factors for 6-month all-cause mortality in old patients with VTE.

[Hemophagocytic lymphohistiocytosis: Analysis of 18 cases]. / Linfohistiocitosis hemofagocítica: análisis de 18 casos.

BACKGROUND AND OBJECTIVE: Hemophagocytic lymphohistiocytosis (HLH) is a serious condition, caused by an improper regulation of the immune response to different stimuli of the immune system. Early diagnosis and treatment are a challenge for the clinician. PATIENTS AND METHOD: We conducted a retrospective study at our institution between 2010 and 2015, of adult patients diagnosed with HLH, in accordance with the criteria of the Histiocyte Society, analyzing their clinical characteristics, diagnostic and etiological studies and the outcome. RESULTS: Eighteen patients were analyzed. Median time to diagnosis was 24 days. We found neoplastic etiology in 8 cases (7 hematologic), while it was infection-related in 6 (4 visceral leishmaniasis), and an inflammatory disease in one. In the remaining 3, an underlying cause for the HLH was not found. Course of treatment was corticosteroids in 16 patients, associated with cyclosporine in 2 of them, one received immunoglobulins, while another received etoposide with tacrolimus. CONCLUSIONS: We emphasize the scarce use of etoposide therapy, the currently recommended treatment. Overall mortality was 44%, mainly associated with neoplastic etiology (67 compared to 16.6% mortality in infection-related etiology, P<.05).

Clinical implications of respiratory virus infections in solid organ transplant recipients: a prospective study.

BACKGROUND: There is limited information about clinical consequences of respiratory virus infections (RVI) in solid organ transplant recipients. No prospective epidemiological study has been published previously. METHODS: We selected a cohort of 152 transplant recipients (cardiac, hepatic and renal transplant recipients). Median time from transplantation was 17 months (range 1-50). They were prospectively followed-up for RVI during 7 months (October to April). Clinical and microbiological evaluation (cell culture, shell vial and polymerase chain reaction technique) of each RVI episode was made. RESULTS: We detected 81 RVI (0.91 episodes/patient/year). Complications were detected in 15/81 episodes (18.5%): acute bronchitis (10 cases), pneumonia (three cases; 3.7% of RVI episodes) and bacterial sinusitis (2 cases). In 4 of 81 episodes (5%), patients needed hospitalization. A respiratory virus was isolated in 17 of 68 nasopharyngeal samples (six respiratory syncytial virus, six influenza, four picornavirus, one adenovirus). Fever presented an 83% positive predictive value for the diagnosis of influenza virus infection among those with a positive microbiological isolation. There were no episodes of acute rejection coincidentally with RVI. Only 54% of the subjects had been previously vaccinated against influenza. CONCLUSIONS: Incidence of RVI among solid organ transplant recipients is similar to general population but complications are higher. A relationship between RVI and rejection was not detected. The rate of influenza vaccination was lower than expected. The presence of fever in a transplant recipient with RVI strongly suggests influenza infection.

Staphylococcus aureus poststernotomy mediastinitis: description of two distinct acquisition pathways with different potential preventive approaches.

OBJECTIVE: Determining the acquisition routes of infection is crucial to designing specific preventive approaches against Staphylococcus aureus poststernotomy mediastinitis. METHODS: From 2002 to 2004, a nasal sample was obtained from patients before cardiac surgery. We collected clinical and microbiologic data of all episodes of S aureus poststernotomy mediastinitis. A case-control study (3:1) was performed to confirm the role of previous preoperative nasal colonization by S aureus as a risk factor for S aureus poststernotomy mediastinitis. Pulsed field gel electrophoresis molecular analysis of nasal and surgical site S aureus isolates was performed to analyze their relatedness in each patient with poststernotomy mediastinitis and with other patients of the study cohort. RESULTS: S aureus nasal cultures were positive in 228 (15.9%) of 1432 patients: methicillin-susceptible S aureus in 222 (15.5%) and meticillin-resistant S aureus in 6 (0.4%). S aureus poststernotomy mediastinitis was diagnosed in 17 (1.2%) of 1432 patients: 9 (3.95%) of 228 in colonized patients versus 8 (0.66%) of 1204 in noncolonized patients (P < .0001). Seven of 9 patients (1.2%) with methicillin-susceptible S aureus had an identical isolate by pulsed field gel electrophoresis in preoperative nasal and surgical-site cultures, but no clonal relatedness was shown among the isolates from these 9 patients. None of the 8 patients with methicillin-resistant S aureus poststernotomy mediastinitis had an identical isolate by pulsed field gel electrophoresis in preoperative nasal and surgical-site cultures, and the same clone of methicillin-resistant S aureus was responsible for all these cases. CONCLUSIONS: Endogenous [corrected] nasal colonization often precedes methicillin-resistant S aureus poststernotomy mediastinitis, which suggests that preoperative [corrected] decontamination is adequate for preventing methicillin-susceptible [corrected] S aureus poststernotomy mediastinitis, whereas hospital infection control measures seem to be the major factor for preventing methicillin-resistant S aureus poststernotomy mediastinitis.