Prognostic Understanding, Goals of Care, and Quality of Life in Hospitalized Patients with Leukemia or Multiple Myeloma.

Background: Prior studies reveal a lack of illness understanding and prognostic awareness among patients with hematological malignancies. We evaluated prognostic awareness and illness understanding among patients with acute leukemia and multiple myeloma (MM) and measured patient-hematologist discordance. Methods: We prospectively enrolled patients with acute leukemia and MM at Mount Sinai Hospital or Yale New Haven Hospital between August 2015 and February 2020. Patients were administered a survey assessing prognostic awareness, goals of care (GOC), and quality of life. Hematologists completed a similar survey for each patient. We assessed discordance across the cohort of patients and hematologists using the likelihood-ratio chi-square test and within patient-hematologist pairs using the kappa (κ) statistic. Results: We enrolled 185 patients (137 with leukemia and 48 with MM) and 29 hematologists. Among patients, 137 (74%) self-identified as White, 27 (15%) as Black, and 21 (11%) as Hispanic. Across the entire cohort, patients were significantly more optimistic about treatment goals compared with hematologists (p = 0.027). Within patient-hematologist pairs, hematologists were significantly more optimistic than patients with respect to line of treatment (κ = 0.03). For both leukemia and MM cohorts, patients were significantly more likely to respond "don't know" or deferring to a faith-based response with 88 (64%) and 34 (71%), respectively, compared with only 28 (20%) and 11 (23%) of hematologists, respectively. Conclusions: We observed significant discordance regarding prognosis and GOC among patients with hematological malignancies and their hematologists. These data support future interventions to improve prognostic understanding among this patient population to facilitate informed treatment choices.

Temporal relationship between sarcoidosis and malignancies in a nationwide cohort of 1942 patients.

PURPOSE: To investigate the phenotype of sarcoidosis according to the time when a malignancy is diagnosed (preexisting to the diagnosis of sarcoidosis, concomitant, or sequential) and to identify prognostic factors associated with malignancies in a large cohort of patients with sarcoidosis. METHODS: We searched for malignancies in the SARCOGEAS cohort, a multicenter nationwide database of consecutive patients diagnosed with sarcoidosis according to the ATS/ESC/WASOG criteria. Solid malignancies were classified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) nomenclature, and hematological malignancies using the 2016 WHO classification. We excluded patients with a biopsy-proven diagnosis of sarcoidosis based exclusively on demonstrating granulomas in tissues also involved by malignant cells. RESULTS: Out of 1942 patients with sarcoidosis, 233 (12%) developed 250 malignancies, including solid (n = 173), hematological (n = 57), and both types of malignancies (n = 3). Concerning the time interval between the diagnoses of both conditions, 83 (36%) patients were diagnosed with malignancy at least 1 year before sarcoidosis diagnosis, 22 (9%) had s synchronous diagnosis of both diseases, and 118 (51%) developed malignancies at least 1 year after the diagnosis of sarcoidosis (the remaining cases developed malignancies in different time intervals). The multivariate-adjusted model showed that individuals with sarcoidosis who developed a malignancy had an hazard ratio (HR) of 2.27 [95% confidence interval (CI), 1.62-3.17] for having an asymptomatic clinical phenotype at diagnosis of sarcoidosis and that spleen (presence vs. absence: HR = 2.06; 95% CI, 1.21-3.51) and bone marrow (presence vs. absence: HR = 3.04; 95% CI, 1.77-5.24) involvements were independent predictors for the development of all-type malignancies. No predictive factors were identified when the analysis was restricted to the development of solid malignancies. The analysis limited to the development of hematological malignancies confirmed the presence of involvement in the spleen (HR = 3.73; 95% CI, 1.38-10.06) and bone marrow (presence vs. absence: HR = 8.00; 95% CI, 3.15-20.35) at the time of sarcoidosis diagnosis as predictive factors. CONCLUSION: It is essential to consider the synchronous or metachronous timing of the diagnosis of malignancies in people with sarcoidosis. We found that half of the malignancies were diagnosed after a diagnosis of sarcoidosis, with spleen and bone marrow involvement associated with a four to eight times higher risk of developing hematological malignancies. Key messages What is already known on this topic Malignancies are one of the comorbidities more frequently encountered in people with sarcoidosis What this study adds Malignancies occur in 12% of patients with sarcoidosis Malignancy may precede, coincide with, or follow the diagnosis of sarcoidosis One-third were identified before sarcoidosis, and half were diagnosed after Spleen and bone marrow involvement are risk factors for developing hematological malignancies How this study might affect research, practice or policy Patients with sarcoidosis should be regularly monitored for neoplasms, informed of the increased risk, and educated on early detection. Those with spleen or bone marrow involvement must be closely followed.

Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma.

BACKGROUND: Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs. METHODS: Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression. RESULTS: Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4-8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4-14) and 55 (95 %CI 41-not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HRadj 1.14; 95 %CI 1.01-1.29; HRadj 1.29; 95 %CI 1.12-1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02-1.72) and OS (HRadj 1.34; 95 %CI 0.99-1.82) compared with corticosteroids alone. CONCLUSIONS: High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.

Enfermedad de Castleman, fisiopatología, avances en el diagnóstico y tratamiento / Castleman's disease, pathophysiology, advances in diagnosis and treatment

La enfermedad de Castleman (EC) engloba a un conjunto heterogéneo de procesos linfoproliferativos que comparten rasgos histológicos bien definidos. Se considera una enfermedad rara o minoritaria u su incidencia no es del todo conocida, aunque se estima en menos de uno por cada 100.000 habitantes. Tiene una distribución bimodal (30-40 años y luego los 60-80 años). Su incidencia es similar en ambos sexos, aunque la variante unicéntrica parece tener ligero predominio en mujeres con proporción 2:1. La EC se clasifica en una forma hialinovascular (siendo esta la más frecuente) y otra plasmocelular, relacionadas con el virus de la inmunodeficiencia humana (VIH) y el virus herpes humano tipo 8 (VHH-8), que junto a otros mecanismos autoinmunitarios desarrollan la hiperproducción de interleucina-6 (IL-6) por parte de los linfocitos B. Existen diferentes líneas de tratamiento, donde destaca el uso de anti IL-6, siendo el siltuximab el más utilizado y catalogado como el fármaco huérfano de esta patología.(AU)

Castleman's disease (CD) encompasses a heterogeneous set of reactive lymphoproliferative processes that share well-defined histologic features. CD is considered a rare or minority disease. The incidence of CD is not fully known, although it is estimated at less than 1 per 100,000 inhabitants. It has a bimodal distribution (30–40 years and then 60–80 years). The incidence is similar in both sexes, although the unicentric variant seems to have a slight predominance in women with a 2:1 ratio. CD is classified into a hyalinovascular form (this being the most frequent) and a plasmocellular form, related to the HIV and VHH-8 viruses, which together with other autoimmune mechanisms develop hyperproduction of interleukin-6 (IL-6) by B lymphocytes. There are different lines of treatment, where the use of anti IL-6 stands out, being siltuximab the most used as orphan drug in this pathology.(AU)

[Castleman's disease, pathophysiology, advances in diagnosis and treatment]. / Enfermedad de Castleman, fisiopatología, avances en el diagnóstico y tratamiento.

Castleman's disease (CD) encompasses a heterogeneous set of reactive lymphoproliferative processes that share well-defined histologic features. CD is considered a rare or minority disease. The incidence of CD is not fully known, although it is estimated at less than 1 per 100,000 inhabitants. It has a bimodal distribution (30-40 years and then 60-80 years). The incidence is similar in both sexes, although the unicentric variant seems to have a slight predominance in women with a 2:1 ratio. CD is classified into a hyalinovascular form (this being the most frequent) and a plasmocellular form, related to the HIV and VHH-8 viruses, which together with other autoimmune mechanisms develop hyperproduction of interleukin-6 (IL-6) by B lymphocytes. There are different lines of treatment, where the use of anti IL-6 stands out, being siltuximab the most used as orphan drug in this pathology.

Characterisation of the coexistence between sarcoidosis and Sjögren's syndrome. Analysis of 43 patients.

OBJECTIVES: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS). METHODS: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies. RESULTS: We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases. CONCLUSIONS: We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.

Therapy-resistant dermatomyositis with extensive 'lumbar belt' calcinosis.

Calcinosis cutis (CC) is the umbrella term for calcium salt deposition on skin and subcutaneous tissue. We present a unique case of CC associated with anti-Mi2-positive dermatomyositis, having a distinctive distribution of subcutaneous calcifications appearing as a 'lumbar belt'. Treatment of CC remains challenging for clinicians due to a lack of high-quality evidence. Corticosteroids, methotrexate, bisphosphonates, intravenous immunoglobulin replacement, rituximab and sodium thiosulfate failed to halt calcinosis progression in this case. Newer therapies, such as Janus kinase inhibitors, should be considered.

Immunotherapy Outcomes in Individuals With Non-Small Cell Lung Cancer and Poor Performance Status.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) treated in real-world practice typically have worse performance status (PS) compared with clinical trial patients, and the effectiveness of immunotherapy in this population in unknown. In this study, we assessed the effectiveness of standard of care immunotherapy for the first-line treatment of stage IV patients with NSCLC with Eastern Cooperative Oncology Group (ECOG) PS greater than or equal to 2. METHODS: We selected ECOG PS greater than or equal to 2 patients from real-world oncology data from a deidentified database and included them if they were diagnosed with stage IV NSCLC and had documented Programmed death-ligand 1 [PD-(L)1] expression greater than 0. Patients with tumor PD-(L)1 expression of at least 50% treated with pembrolizumab monotherapy were compared with those who did not have any documented treatment. Patients with tumor PD-(L)1 expression less than 50% treated with pembrolizumab and chemotherapy were compared with those treated with pembrolizumab monotherapy and those without documented treatment. RESULTS: In our propensity score-adjusted analysis, patients with ECOG PS of at least 2 and tumor PD-(L)1 expression of at least 50% treated with pembrolizumab monotherapy had statistically significantly better real-world overall survival compared with those without documented treatment (adjusted hazard ratio [HR] = 0.39, 95% confidence internal [CI] = 0.32 to 0.47). For patients with tumor PD-(L)1 expression less than 50%, there was also a statistically significant real-world overall survival benefit for those who received treatment either with combination pembrolizumab plus chemotherapy (adjusted HR = 0.39, 95% CI = 0.32 to 0.46) or pembrolizumab monotherapy (adjusted HR = 0.55, 95% CI = 0.41 to 0.70) compared with patients receiving no documented treatment. CONCLUSIONS: Among a highly representative sample of patients with advanced NSCLC and poor PS, our findings suggest that immunotherapy may provide an important survival benefit in individuals with high PD-(L)1-expressing tumors and in conjunction with chemotherapy in tumors with low PD-(L)1 expression.

Sorption/Desorption and Kinetics of Atrazine, Chlorfenvinphos, Endosulfan Sulfate and Trifluralin on Agro-Industrial and Composted Organic Wastes.

The use of pesticides presents a risk to terrestrial and aquatic ecosystems. For this reason, the development of strategies to prevent and restore pollution is of the greatest interest, including the adsorption to organic matter. The aim of the present study was to investigate the sorption/desorption and kinetics of atrazine, chlorfenvinphos, endosulfan sulfate, and trifluralin onto several raw organic wastes by batch experiments. Three kinetic models were used to fit the obtained sorption kinetics data and two to fit the obtained adsorption isotherm data; both the Freundlich and pseudo-second-order kinetic models described the sorption isotherms well. The desorption study revealed hysteresis in all cases, showing strong, and not completely reversible, adsorption in most cases, with the exception of atrazine-sawdust and chlorfenvinphos-sawdust and chicken manure combinations, for which responses were weak and irreversible. The best kinetic, adsorption and desorption constants were achieved for the hydrophobic pesticides. With respect to sorption-desorption rates, orujillo was found to be the best adsorbent for atrazine, while composted urban solid waste was more suitable for trifluralin and endosulfan sulfate. Sorption constants and simple correlations indicated that, not only the organic matter content, but also the nature of the organic matter itself, and the pesticide and adsorbent properties, determine pesticide sorption-desorption. The use of wastes as efficient and cheap adsorbents for reducing the risk of pesticide pollution is proposed.

Disparities in Supportive Care Needs Over Time Between Racial and Ethnic Minority and Non-Minority Patients With Advanced Lung Cancer.

CONTEXT: Little is known about inequities in supportive care needs among diverse patients with advanced lung cancer. OBJECTIVES: We aimed to examine differences in supportive care needs between racial/ethnic minority and non-minority patients with lung cancer and identify how these needs change over time. METHODS: We performed a prospective cohort study of patients newly diagnosed with advanced lung cancer (stage III and IV). Patients completed a validated survey at baseline, 4-, 8- and 12-months post-diagnosis, assessing supportive care needs: medical communication/information, psychological/emotional support, daily living, financial concerns, physical symptoms, and spiritual and social needs. Univariable and multivariable regression analyses compared differences in supportive care needs between minority (Black and Latinx) and non-minority patients. A mixed effect model with minority status, follow-up time and the interaction between minority status and time assessed the association between each need and minority status with changes over time. RESULTS: We enrolled 99 patients; 55 (56%) were minorities and 44 (44%) were non-minorities. At baseline, minorities reported significantly higher needs across each domain except medical communication/information. Over time, these reported differences remained consistent except for medical communication. After adjustment, the needs of both minorities and non-minorities increased significantly in the psychological/emotional, daily living and physical symptom domains. CONCLUSION: Minority patients with advanced lung cancer are more likely to have higher baseline and persistent supportive care needs relatives to non-minority patients. Clinicians caring for minority patients with lung cancer should provide targeted supportive care evaluation and treatment to ensure health equity.

Guidelines for surfactant selection to treat petroleum hydrocarbon-contaminated soils.

The present study determined the most effective surfactants to remediate gasoline and diesel-contaminated soil integrating information from soil texture and soil organic matter. Different ranges for aliphatic and aromatic hydrocarbons (> C6-C8, > C8-C10, > C10-C12, > C12-C16, > C16-C21, and > C21-C35) in gasoline and diesel fuel were analyzed. This type of analysis has been investigated infrequently. Three types of soils (silty clay, silt loam, and loamy sand) and four surfactants (non-ionic: Brij 35 and Tween 80; anionic: SDBS and SDS) were used. The results indicated that the largest hydrocarbon desorption was 56% for silty clay soil (SDS), 59% for silt loam soil (SDBS), and 69% for loamy sand soil (SDS). Soils with large amounts of small particles showed the worst desorption efficiencies. Anionic surfactants removed more hydrocarbons than non-ionic surfactants. It was notable that preferential desorption on different hydrocarbon ranges was observed since aliphatic hydrocarbons and large ranges were the most recalcitrant compounds of gasoline and diesel fuel components. Unlike soil texture, natural organic matter concentration caused minor changes in the hydrocarbon removal rates. Based on these results, this study might be useful as a tool to select the most cost-effective surfactant knowing the soil texture and the size and chemical structure of the hydrocarbons present in a contaminated site.

Cutaneous and Ganglion Sarcoidosis Induced by Polycaprolactone Facial Filler: A New Expression of ASIA Syndrome?

Dermal fillers are applied using a minimally invasive technique with a good safety profile. However, they can have side effects. We present the case of a patient who, 2 months after undergoing polycaprolactone (Ellansé®) injections, developed nodular facial and nodal lesions that were compatible with sarcoidosis on histology. This complication has not been previously described for polycaprolactone and could be the expression of an autoimmune syndrome induced by adjuvants. LEARNING POINTS: Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) is a recently devised umbrella term for autoimmune diseases caused by adjuvants.Aesthetic procedures, which are increasingly common, may be a cause of ASIA syndrome.Polycaprolactone is a bioabsorbable polymer with a safe profile but can have adverse events, including systemic sarcoidosis.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

A Multi-Omics Approach Reveals New Signatures in Obese Allergic Asthmatic Children.

Background: Asthma is a multifactorial condition where patients with identical clinical diagnoses do not have the same clinical history or respond to treatment. This clinical heterogeneity is reflected in the definition of two main endotypes. We aimed to explore the metabolic and microbiota signatures that characterize the clinical allergic asthma phenotype in obese children. Methods: We used a multi-omics approach combining clinical data, plasma and fecal inflammatory biomarkers, metagenomics, and metabolomics data in a cohort of allergic asthmatic children. Results: We observed that the obese allergic asthmatic phenotype was markedly associated with higher levels of leptin and lower relative proportions of plasma acetate and a member from the Clostridiales order. Moreover, allergic children with a worse asthma outcome showed higher levels of large unstained cells, fecal D lactate and D/L lactate ratio, and with a higher relative proportion of plasma creatinine and an unclassified family member from the RF39 order belonging to the Mollicutes class. Otherwise, children with persistent asthma presented lower levels of plasma citrate and dimethylsulfone. Conclusion: Our integrative approach shows the molecular heterogeneity of the allergic asthma phenotype while highlighting the use of omics technologies to examine the clinical phenotype at a more holistic level.

Climate change effects on plant-soil feedbacks and consequences for biodiversity and functioning of terrestrial ecosystems.

Plant-soil feedbacks (PSFs) are interactions among plants, soil organisms, and abiotic soil conditions that influence plant performance, plant species diversity, and community structure, ultimately driving ecosystem processes. We review how climate change will alter PSFs and their potential consequences for ecosystem functioning. Climate change influences PSFs through the performance of interacting species and altered community composition resulting from changes in species distributions. Climate change thus affects plant inputs into the soil subsystem via litter and rhizodeposits and alters the composition of the living plant roots with which mutualistic symbionts, decomposers, and their natural enemies interact. Many of these plant-soil interactions are species-specific and are greatly affected by temperature, moisture, and other climate-related factors. We make a number of predictions concerning climate change effects on PSFs and consequences for vegetation-soil-climate feedbacks while acknowledging that they may be context-dependent, spatially heterogeneous, and temporally variable.