Explore the vast range of titles available.

Recent observational and modeling studies suggest that stratospheric ozone depletion not only influences the surface climate in the Southern Hemisphere (SH), but also impacts Northern Hemisphere (NH) spring, which implies a strong interaction between dynamics and chemistry. Here, we systematically analyze the importance of interactive chemistry with respect to the representation of stratosphere–troposphere coupling and in particular the effects on NH surface climate during the recent past. We use the interactive and specified chemistry version of NCAR's Whole Atmosphere Community Climate Model coupled to an ocean model to investigate differences in the mean state of the NH stratosphere as well as in stratospheric extreme events, namely sudden stratospheric warmings (SSWs), and their surface impacts. To be able to focus on differences that arise from two-way interactions between chemistry and dynamics in the model, the specified chemistry model version uses a time-evolving, model-consistent ozone field generated by the interactive chemistry model version. We also test the effects of zonally symmetric versus asymmetric prescribed ozone, evaluating the importance of ozone waves in the representation of stratospheric mean state and variability. The interactive chemistry simulation is characterized by a significantly stronger and colder polar night jet (PNJ) during spring when ozone depletion becomes important. We identify a negative feedback between lower stratospheric ozone and atmospheric dynamics during the breakdown of the stratospheric polar vortex in the NH, which contributes to the different characteristics of the PNJ between the simulations. Not only the mean state, but also stratospheric variability is better represented in the interactive chemistry simulation, which shows a more realistic distribution of SSWs as well as a more persistent surface impact afterwards compared with the simulation where the feedback between chemistry and dynamics is switched off. We hypothesize that this is also related to the feedback between ozone and dynamics via the intrusion of ozone-rich air into polar latitudes during SSWs. The results from the zonally asymmetric ozone simulation are closer to the interactive chemistry simulations, implying that under a model-consistent ozone forcing, a three-dimensional (3-D) representation of the prescribed ozone field is desirable. This suggests that a 3-D ozone forcing, as recommended for the upcoming CMIP6 simulations, has the potential to improve the representation of stratospheric dynamics and chemistry. Our findings underline the importance of the representation of interactive chemistry and its feedback on the stratospheric mean state and variability not only in the SH but also in the NH during the recent past.

Background: In 2019, a new coronavirus disease emerged in Wuhan, China, known as SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, and caused an ongoing pandemic. Symptomatology of the syndrome is variable, with complications extending to hematopoiesis and hemostasis. Approximately a year after onset of the virus, four vaccination formulas became available to the public, based on a viral vector or mRNA technology. These vaccine formulas have been hampered with hematological complications, like vaccine-induced immune thrombotic thrombocytopenia (VITT) and vaccine-related ITP (immune thrombocytopenic purpura). ITP is a disease with autoimmune pathogenesis characterized by antibody production against platelets and an increased hemorrhagic risk. A decent number of cases have been referred to as possible adverse effects of COVID-19 vaccinations. Case presentation: in this case report, we present two cases of newly diagnosed ITP after vaccination with ChAdOx1-S (AstraZeneca), with a good response to treatment with thrombopoietin-receptor agonists (TPO-RAs). Discussion: we observed an absence of response after corticosteroids and IVIG therapy and a positive therapeutic outcome on TPO-RA. Conclusions: in the ongoing pandemic, there is an urgent need to create therapeutic guidelines for vaccination-related clinical entities and to clarify indications for the vaccination of patients with pre-existing hematological diseases.

The BRAF-V600E mutation has been established as a signature alteration occurring almost universally in hairy cell leukemia. Moreover, it can be detected in a small percentage of patients with non-small cell lung cancer. We report the case of a patient with a metastatic BRAF-V600E-mutated lung adenocarcinoma suffering from concomitant hairy cell leukemia. The identification of an identical BRAF mutation in both malignancies raises physiopathological considerations and might offer unique therapeutic strategies for this group of patients.

Southern Hemisphere lower-stratospheric ozone depletion has been shown to lead to a poleward shift of the tropospheric jet stream during austral summer, influencing surface atmosphere and ocean conditions, such as surface temperatures and sea ice extent. The characteristics of stratospheric and tropospheric responses to ozone depletion, however, differ among climate models depending on the representation of ozone in the models. The most appropriate way to represent ozone in a model is to calculate it interactively. However, due to computational costs, in particular for long-term coupled ocean–atmosphere model integrations, the more common way is to prescribe ozone from observations or calculated model fields. Here, we investigate the difference between an interactive and a specified chemistry version of the same atmospheric model in a fully coupled setup using a nine-member chemistry–climate model ensemble. In the specified chemistry version of the model the ozone fields are prescribed using the output from the interactive chemistry model version. We use daily resolved ozone fields in the specified chemistry simulations to achieve a very good comparability between the ozone forcing with and without interactive chemistry. We find that although the shortwave heating rate trend in response to ozone depletion is the same in the different chemistry settings, the interactive chemistry ensemble shows a stronger trend in polar cap stratospheric temperatures (by about 0.7 K decade−1) and circumpolar stratospheric zonal mean zonal winds (by about 1.6 m s−1 decade−1 as compared to the specified chemistry ensemble. This difference between interactive and specified chemistry in the stratospheric response to ozone depletion also affects the tropospheric response. However, an impact on the poleward shift of the tropospheric jet stream is not detected. We attribute part of the differences found in the experiments to the missing representation of feedbacks between chemistry and dynamics in the specified chemistry ensemble, which affect the dynamical heating rates, and part of it to the lack of spatial asymmetries in the prescribed ozone fields. This effect is investigated using a sensitivity ensemble that was forced by a three-dimensional instead of a two-dimensional ozone field. This study emphasizes the value of interactive chemistry for the representation of the Southern Hemisphere stratospheric-jet response to ozone depletion and infers that for periods with strong ozone variability (trends) the details of the ozone forcing could also have an influence on the representation of southern-hemispheric climate variability.

In a recent study it was illustrated that the El Nino Southern Oscillation (ENSO) mode can exist in the absence of any ocean dynamics. This oscillating mode exists just due to the interaction between atmospheric heat fluxes and ocean heat capacity. The primary purpose of this study is to further explore these atmospheric Slab Ocean ENSO dynamics and therefore the role of positive atmospheric feedbacks in model simulations and observations. The positive solar radiation feedback to sea surface temperature (SST), due to reduced cloud cover for anomalous warm SSTs, is the main positive feedback in the Slab Ocean El Nino dynamics. The strength of this positive cloud feedback is strongly related to the strength of the equatorial cold tongue. The combination of positive latent and sensible heat fluxes to the west and negative ones to the east of positive anomalies leads to the westward propagation of the SST anomalies, which allows for oscillating behavior with a preferred period of 6–7 years. Several indications are found that parts of these dynamics are indeed observed and simulated in other atmospheric or coupled general circulation models (AGCMs or CGCMs). The CMIP3 AGCM-slab ensemble of 13 different AGCM simulations shows unstable ocean–atmosphere interactions along the equatorial Pacific related to stronger cold tongues. In observations and in the CMIP3 and CMIP5 CGCM model ensemble the strength and sign of the cloud feedback is a function of the strength of the cold tongue. In summary, this indicates that the Slab Ocean El Nino dynamics are indeed a characteristic of the equatorial Pacific climate that is only dominant or significantly contributing to the ENSO dynamics if the SST cold tongue is sufficiently strong. In the observations this is only the case during strong La Nina conditions. The presence of the Slab Ocean ENSO atmospheric feedbacks in observations and CGCM model simulations implies that the family of physical ENSO modes does have another member, which is entirely driven by atmospheric processes and does not need to have the same spatial pattern nor the same time scales as the main ENSO dynamics.

Major sudden stratospheric warmings (SSWs) are extreme events during boreal winter,which not only impact tropospheric weather up to three months but also can influence oceanic variability through wind stress and heat flux anomalies. In the North Atlantic region, SSWs have the potential to modulate deep convection in the Labrador Sea and thereby the strength of the Atlantic meridional overturning circulation. The impact of SSWs on the Northern Hemisphere surface climate is investigated in two coupled climate models: a stratosphere-resolving (high top) and a non-stratosphere-resolving (low top) model. In both configurations, a robust link between SSWs and a negative NAO is detected, which leads to shallower-than-normal North Atlantic mixed layer depth. The frequency of SSWs and the persistence of this link is better captured in the high-top model. Significant differences occur over the Pacific region, where an unrealistically persistent Aleutian low is observed in the low-top configuration. An overrepresentation of SSWs during El Niño conditions in the low-top model is the main cause for this artifact. Our results underline the importance of a proper representation of the stratosphere in a coupled climatemodel for a consistent surface response in both the atmosphere and the ocean, which, among others, may have implications for oceanic deep convection in the subpolar North Atlantic.

Lenalidomide has particular activity in patients with transfusion-dependent del(5q) myelodysplastic syndromes (MDS), but mechanistic information is limited regarding the relationship between erythroid and cytogenetic responses. We reviewed medical records from three distinct subgroups of del(5q) MDS patients who had unexpected effects with lenalidomide treatment: 1. two patients with complex karyotypes who achieved both cytogenetic remissions and transfusion independence; 2. two patients with 5q- syndrome who took lenalidomide for less than 12 weeks but remained transfusion independent for 15+ months still displaying del(5q) metaphases after 6 and 12 months; and 3. one patient who was a non-responder on lenalidomide during treatment but became transfusion independent for 13+ months after discontinuation. All but the latter patient in this series had reduction of affected metaphases, suggesting that erythroid responses might be mediated by result from partial or complete suppression of the malignant clone, either directly or indirectly through modulation of the bone marrow microenvironment. These clinical observations illustrate the heterogeneity of del(5q)MDS pathogenesis and the diversity of lenalidomide responses within this patient subset.

Lenalidomide is a novel thalidomide analogue with enhanced immunomodulatory and antiangiogenic action lacking most of the typical thalidomide-associated adverse events. In myelodysplastic syndromes (MDS), it has been used primarily in the IPSS low- and intermediate-1 risk setting. Several trials have demonstrated its potential to lead to both erythroid and cytogenetic responses in these disease groups. In a clinical trial of patients with a del(5q) chromosomal abnormality, lenalidomide treatment resulted in red blood cell (RBC) transfusion independence in 67% of patients. Moreover, 45% of patients achieved a complete cytogenetic remission, and 28% achieved a minor cytogenetic remission. This result was independent of karyotype complexity. Lenalidomide might also induce long-term remissions in del(5q) patients with an elevated medullary blast count. In non-del(5q) patients, 43% of patients with confirmed low- and intermediate-1 risk achieved transfusion independence or a reduction of at least 50% of pre-treatment RBC transfusion levels. Adverse events are common but manageable and include neutropenia and thrombocytopenia, pruritus, rash, diarrhea, and others. Lenalidomide will prove an essential part in the armamentarium of MDS therapeutics. Combination therapies with cytokines, demethylating agents, tyrosine kinase inhibitors, or chemotherapy are being investigated and may show additional benefit in both low- and high risk MDS.

All-trans-retinoic acid (ATRA) alone or in combination with cytokines and vitamins has been shown to stimulate erythropoiesis in low-risk myelodysplastic syndromes (MDS). We performed a phase II study on 29 patients with MDS and isolated del(5q) including bands q31-q33 to determine the efficacy and safety of ATRA in combination with tocopherol-alpha. All patients had low/intermediate-1 risk MDS according to the international prognostic scoring system. They received 45 mg/m(2) ATRA on days 1 to 90, and 90 mg/m(2) on days 91 to 180. Tocopherol dosage was 600 IU three times daily. Twenty-four patients completed dose level I, and 12 patients dose level II. Eighty-six percent of patients experienced side effects. Thirty discontinued the drug treatment due to such events as skin reactions, cheilitis, conjunctivitis, joint pain, creatinine increase, or CNS symptoms. One patient (3%) achieved a major erythroid response resulting in transfusion independence throughout the study. Four patients (14%) achieved a minor erythroid response with >50% reduction of transfusion needs. None of the participants had a cytogenetic response. There was no significant improvement in quality of life among responding patients as measured by the European Organization for the Research and Treatment of Cancer (EORTC) quality of life questionnaire. Based on these results, the combination of ATRA and tocopherol-alpha is not recommended for the treatment of del(5q) MDS.

All-trans-retinoic acid (ATRA) alone or in combination with cytokines and vitamins has been shown to stimulate erythropoiesis in low-risk myelodysplastic syndromes (MDS). We performed a phase II study on 29 patients with MDS and isolated del(5q) including bands q31-q33 to determine the efficacy and safety of ATRA in combination with tocopherol-α. All patients had low/intermediate-1 risk MDS according to the international prognostic scoring system. They received 45 mg/m^sup 2^ ATRA on days 1 to 90, and 90 mg/m^sup 2^ on days 91 to 180. Tocopherol dosage was 600 IU three times daily. Twenty-four patients completed dose level I, and 12 patients dose level II. Eighty-six percent of patients experienced side effects. Thirty discontinued the drug treatment due to such events as skin reactions, cheilitis, conjunctivitis, joint pain, creatinine increase, or CNS symptoms. One patient (3%) achieved a major erythroid response resulting in transfusion independence throughout the study. Four patients (14%) achieved a minor erythroid response with >50% reduction of transfusion needs. None of the participants had a cytogenetic response. There was no significant improvement in quality of life among responding patients as measured by the European Organization for the Research and Treatment of Cancer (EORTC) quality of life questionnaire. Based on these results, the combination of ATRA and tocopherol-α is not recommended for the treatment of del(5q) MDS.[PUBLICATION ABSTRACT]