Patient and public involvement in abortion research: reflections from the Shaping Abortion for Change (SACHA) Study.

Patient and public involvement (PPI) is limited within abortion-related research. Possible reasons for this include concerns about engaging with a stigmatised patient group who value confidentiality and may be reluctant to re-engage with services. Structural barriers, including limited funding for abortion-related research, also prevent researchers from creating meaningful PPI opportunities. Here, we describe lessons learnt on undertaking PPI as part of the Shaping Abortion for Change (SACHA) Study, which sought to create an evidence base to guide new directions in abortion care in Britain.Two approaches to PPI were used: involving patients and the public in the oversight of the research and its dissemination as lay advisors, and group meetings to obtain patients' views on interpretation of findings and recommendations. All participants observed the SACHA findings aligned with their own experiences of having an abortion in Britain. These priorities aligned closely with those identified in a separate expert stakeholder consultation undertaken as part of the SACHA Study. One additional priority which had not been identified during the research was identified by the PPI participants.We found abortion patients to be highly motivated to engage in the group meetings, and participation in them actively contributed to the destigmatisation of abortion by giving them a space to share their experiences. This may alleviate any ethical concerns about conducting research and PPI on abortion, including the assumption that revisiting an abortion experience will cause distress. We hope that our reflections are useful to others considering PPI in abortion-related research and service improvement.

Impact of approval of home use of misoprostol in England on access to medical abortion: An interrupted time series analysis.

OBJECTIVE: In 2018, the Department of Health and Social Care in England approved the use of misoprostol at home for early medical abortions, following administration of mifepristone at clinic. The objective of the present study was to assess the impact of the approval of home administration of misoprostol in England on access to medical abortion, assessed through proxy measures of the proportion of all abortions that were medical and gestational age. METHODS: This study uses the clinical data from the British Pregnancy Advisory Service on abortions in England in years 2018-2019, containing demographic and procedure characteristics of patients. We conducted an interrupted time series analysis to establish the differences before and after the approval in access to medical abortion, measured by the proportion of all abortions that were medical, and gestational age. The analysis also examined whether these changes were equitable, with focus on area-level deprivation. RESULTS: The analysis of the data (145 529 abortions) suggested that there was an increase in the proportion of medical abortions and decrease in gestational age of abortions after the approval. Compared with the situation if former trends had continued, the actual proportion of early medical abortions was 4.2% higher in December 2019, and the mean gestational age 3.4 days lower. We found that the acceleration of existing trends in increase in proportion of medical abortions and decrease in gestational age were larger in the most deprived quintiles and in those reporting a disability, but not equal across ethnic groups, with Black and Black British women experiencing little change in trajectories post-approval. CONCLUSION: The approval of home use of misoprostol as part of an early medical abortion regimen in England was associated with material and equitable improvements in abortion access. Pre-approval trends toward greater uptake of medical abortion and declining gestational age were accelerated post-approval and were greatest in the most deprived areas of England, but not across all racial/ethnic groups. The present findings strongly support the continuation or introduction of home management of medical abortions.

HPV Vaccination among Polish Adolescents-Results from POLKA 18 Study.

Human Papillomavirus (HPV) is the main cause of cervical cancer and genital warts and constitutes one of the most common sexually transmitted infections. Cervical cancer is the only reproductive cancer that has a primary prevention programme through the introduction of HPV vaccinations. Even though the majority of European countries have nationally funded HPV vaccination programmes, in Poland these are exclusively local and scarcely funded. Moreover, the majority of local programmes are directed to females only. Meanwhile, Poland has one of the highest cervical cancer incidence rates among high income countries. The aim of this study was to measure HPV vaccination levels among final-year students in Poland and to establish the association between vaccination status and gender, region and level of sexual education received. This study is a part of the POLKA 18 Study, which used original self-reported paper-based questionnaires distributed in schools in six Polish regions. The study was conducted between April and December 2019. The obtained data were analysed in STATA 17. In total, 2701 fully completed questionnaires were collected. Over half of the respondents (58.2%) did not know their HPV vaccination status. Only 16.0% of the respondents replied that they have been vaccinated against HPV (18.2% of females and 14.5% of males). There was no direct association between vaccination status and access to 'family life education' classes. The vaccination level significantly differed among the different regions of Poland (p < 0.0001), with the Slaskie and Wielkopolskie regions achieving the highest rates. At least a quarter of adolescents after their sexual debut have not been vaccinated against HPV. Regions with immunization programmes introduced to their provincial capitals had higher vaccination rates. Our findings indicate the need for the introduction of state-funded vaccination programmes at the national level for the vaccination rate to increase, which will have the potential to decrease cervical cancer incidence in the country.

Improving experience of medical abortion at home in a changing therapeutic, technological and regulatory landscape: a realist review.

OBJECTIVE: To inform UK service development to support medical abortion at home, appropriate for person and context. DESIGN: Realist review SETTING/PARTICIPANTS: Peer-reviewed literature from 1 January 2000 to 9 December 2021, describing interventions or models of home abortion care. Participants included people seeking or having had an abortion. INTERVENTIONS: Interventions and new models of abortion care relevant to the UK. OUTCOME MEASURES: Causal explanations, in the form of context-mechanism-outcome configurations, to test and develop our realist programme theory. RESULTS: We identified 12 401 abstracts, selecting 944 for full text assessment. Our final review included 50 papers. Medical abortion at home is safe, effective and acceptable to most, but clinical pathways and user experience are variable and a minority would not choose this method again. Having a choice of abortion location remains essential, as some people are unable to have a medical abortion at home. Choice of place of abortion (home or clinical setting) was influenced by service factors (appointment number, timing and wait-times), personal responsibilities (caring/work commitments), geography (travel time/distance), relationships (need for secrecy) and desire for awareness/involvement in the process. We found experiences could be improved by offering: an option for self-referral through a telemedicine consultation, realistic information on a range of experiences, opportunities to personalise the process, improved pain relief, and choice of when and how to discuss contraception. CONCLUSIONS: Acknowledging the work done by patients when moving medical abortion care from clinic to home is important. Patients may benefit from support to: prepare a space, manage privacy and work/caring obligations, decide when/how to take medications, understand what is normal, assess experience and decide when and how to ask for help. The transition of this complex intervention when delivered outside healthcare environments could be supported by strategies that reduce surprise or anxiety, enabling preparation and a sense of control.

Aboveground plant-to-plant electrical signaling mediates network acquired acclimation.

Systemic acquired acclimation and wound signaling require the transmission of electrical, calcium, and reactive oxygen species (ROS) signals between local and systemic tissues of the same plant. However, whether such signals can be transmitted between two different plants is largely unknown. Here, we reveal a new type of plant-to-plant aboveground direct communication involving electrical signaling detected at the surface of leaves, ROS, and photosystem networks. A foliar electrical signal induced by wounding or high light stress applied to a single dandelion leaf can be transmitted to a neighboring plant that is in direct contact with the stimulated plant, resulting in systemic photosynthetic, oxidative, molecular, and physiological changes in both plants. Furthermore, similar aboveground changes can be induced in a network of plants serially connected via touch. Such signals can also induce responses even if the neighboring plant is from a different plant species. Our study demonstrates that electrical signals can function as a communication link between transmitter and receiver plants that are organized as a network (community) of plants. This process can be described as network-acquired acclimation.

Should COVID-specific arrangements for abortion continue? The views of women experiencing abortion in Britain during the pandemic.

BACKGROUND: During the COVID-19 pandemic, the British governments issued temporary approvals enabling the use of both medical abortion pills, mifepristone and misoprostol, at home. This permitted the introduction of a fully telemedical model of abortion care with consultations taking place via telephone or video call and medications delivered to women's homes. The decision was taken by the governments in England and Wales to continue this model of care beyond the original end date of April 2022, while at time of writing the approval in Scotland remains under consultation. METHODS: We interviewed 30 women who had undergone an abortion in England, Scotland or Wales between August and December 2021. We explored their views on the changes in abortion service configuration during the pandemic and whether abortion via telemedicine and use of abortion medications at home should continue. RESULTS: Support for continuation of the permission to use mifepristone and misoprostol at home was overwhelmingly positive. Reasons cited included convenience, comfort, reduced stigma, privacy and respect for autonomy. A telemedical model was also highly regarded for similar reasons, but for some its necessity was linked to safety measures during the pandemic, and an option to have an in-person interaction with a health professional at some point in the care pathway was endorsed. CONCLUSIONS: The approval to use abortion pills at home via telemedicine is supported by women having abortions in Britain. The voices of patients are essential to shaping acceptable and appropriate abortion service provision.

Photosystem II 22kDa protein level - a prerequisite for excess light-inducible memory, cross-tolerance to UV-C and regulation of electrical signalling.

It is well known that PsbS is a key protein for the proper management of excessive energy in plants. Plants without PsbS cannot trigger non-photochemical quenching, which is crucial for optimal photosynthesis under variable conditions. Our studies showed wild-type plants had enhanced tolerance to UV-C-induced cell death (CD) upon induction of light memory by a blue or red light. However, npq4-1 plants, which lack PsbS, as well as plants overexpressing this protein (oePsbS), responded differently. Untreated oePsbS appeared more tolerant to UV-C exposure, whereas npq4-1 was unable to adequately induce cross-tolerance to UV-C. Similarly, light memory induced by episodic blue or red light was differently deregulated in npq-4 and oePsbS, as indicated by transcriptomic analyses, measurements of the trans-thylakoid pH gradient, chlorophyll a fluorescence parameters, and measurements of foliar surface electrical potential. The mechanism of the foliar CD development seemed to be unaffected in the analysed plants and is associated with chloroplast breakdown. Our results suggest a novel, substantial role for PsbS as a regulator of chloroplast retrograde signalling for light memory, light acclimation, CD, and cross-tolerance to UV radiation.

Electrical Signaling, Photosynthesis and Systemic Acquired Acclimation.

Electrical signaling in higher plants is required for the appropriate intracellular and intercellular communication, stress responses, growth and development. In this review, we have focus on recent findings regarding the electrical signaling, as a major regulator of the systemic acquired acclimation (SAA) and the systemic acquired resistance (SAR). The electric signaling on its own cannot confer the required specificity of information to trigger SAA and SAR, therefore, we have also discussed a number of other mechanisms and signaling systems that can operate in combination with electric signaling. We have emphasized the interrelation between ionic mechanism of electrical activity and regulation of photosynthesis, which is intrinsic to a proper induction of SAA and SAR. In a special way, we have summarized the role of non-photochemical quenching and its regulator PsbS. Further, redox status of the cell, calcium and hydraulic waves, hormonal circuits and stomatal aperture regulation have been considered as components of the signaling. Finally, a model of light-dependent mechanisms of electrical signaling propagation has been presented together with the systemic regulation of light-responsive genes encoding both, ion channels and proteins involved in regulation of their activity. Due to space limitations, we have not addressed many other important aspects of hormonal and ROS signaling, which were presented in a number of recent excellent reviews.

The prognostic significance of surface dipeptidylpeptidase IV (CD26) expression in B-cell chronic lymphocytic leukemia.

A number of factors related to B-cell chronic lymphocytic leukemia (B-CLL) patients' prognosis have been identified. However, still some factors better reflecting disease activity in individual cases are explored. The study aimed to evaluate prognostic significance of dipeptidylpeptidase IV/CD26 expression on B-CLL cells and its relationship with other well established prognostic factors. The study included 94 patients with newly diagnosed B-CLL and involved analysis of clinical, laboratory, flow-cytometry and cytogenetic data. Detailed analysis showed that CD26 expression on B-CLL cells correlates with Rai's clinical stage of the disease at diagnosis (p=0.034), ß2-microglobulin concentration (p=0.012), lactic acid dehydrogenase activity (p=0.045) and absolute lymphocytes' count (p=0.027) in the blood. The multivariate analysis revealed that time to treatment (TTT) was significantly influenced by Rai clinical stage, LDH activity in blood and CD26 expression on B-CLL cell's. Moreover, in the multivariate analysis restricted to the group of patients with documented cytogenetic risk (n=36) CD26 expression, Rai clinical stage and cytogenetic profile remained their independent impact on TTT. The results of our study indicate that the CD26 expression should be incorporated in B-CLL patients risk assessment along with well known prognostic factors, since it seems to have a relationship with the tumor mass and influences TTT.

B-Cell Chronic Lymphocytic Leukemia with 11q22.3 Rearrangement in Patient with Chronic Myeloid Leukemia Treated with Imatinib.

The coexistence of two diseases chronic myeloid leukemia (CML) and B-cell chronic lymphocytic leukemia (B-CLL) is a rare phenomenon. Both neoplastic disorders have several common epidemiological denominators (they occur more often in men over 50 years of age) but different origin and long term prognosis. In this paper we described the clinical and pathological findings in patient with CML in major molecular response who developed B-CLL with 11q22.3 rearrangement and Coombs positive hemolytic anemia during the imatinib treatment. Due to the presence of the symptoms of autoimmune hemolytic anemia and optimal CML response to the imatinib treatment, the decision about combined therapy with prednisone and imatinib was made. During the follow-up, the normalization of complete blood count and resolution of peripheral lymphadenopathy were noted. The hematologic response of B-CLL was diagnosed. The repeated FISH analysis of cultured peripheral blood lymphocytes showed 2% of cells carrying 11q22.3 rearrangement. At the same time, molecular monitoring confirmed the deep molecular response of CML. The effectiveness of such combination in the described case raises the question about the best therapeutic option in such situation, especially in patients with good imatinib tolerance and optimal response.

The JAK2 V617F mutational status and allele burden may be related with the risk of venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms.

INTRODUCTION: Patients with Philadelphia-negative myeloproliferative neoplasms (Ph(-) MPNs) are at increased risk of thromboembolic and hemorrhagic complications. The aim of the study was to determine the relationship between JAK2 V617F mutational status, JAK2 V617F allele burden and the risk of vascular complications occurrence. MATERIALS AND METHODS: Analysis was performed in a cohort of 186 patients diagnosed with polycythemia vera (53), essential thrombocythemia (114), primary myelofibrosis (11), and unclassified MPN (8). The risk of vascular complications development was analyzed in 126 JAK2 V617F-positive patients with respect to allele burden assessed with allele-specific 'real-time' quantitative polymerase chain reaction (AS RQ-PCR). RESULTS: Overall prevalence of any vascular complications was 44.6%. Arterial thrombosis occurred in 20.4%, venous thromboembolism (VTE) in 11.3%, bleeding episodes in 24.7% of patients. Individuals harboring JAK2 V617F mutation, regardless of MPN type, were at higher risk of VTE (OR=5.15, 95%CI: 1.16-22.90, P=0.024), mainly deep vein thrombosis (DVT). JAK2 allele burden higher than 20% identified patients with 7.4-fold increased risk of VTE (95%CI: 1.6-33.7, P=0.004), but not of arterial thrombosis, neither of bleeding complications, and remained the only significant VTE risk factor in multivariate logistic regression. High allele burdens (over 50%) were strikingly associated with proximal DVT cases, but not with distal DVT. CONCLUSIONS: The group of MPN patients with JAK2 V617F allele burden higher than 20% may benefit the most from vigilant monitoring and appropriate prophylaxis against vascular events. Inclusion of JAK2 V617F mutant allele burden in new risk stratifications seems to be justified and requires controlled prospective trials.

Bleeding complications after arthroscopy in a JAK2V617F-positive patient with essential thrombocythemia and acquired von Willebrand syndrome (AVWS).

Acquired von Willebrand syndrome (AVWS) is an acquired bleeding disorder with clinical and laboratory features similar to those of the inherited form of the disease. AVWS is reported in many disorders, most frequently in myeloproliferative neoplasms and in, among others, essential thrombocythemia (ET). Interestingly, ET is associated with both the thrombotic and haemorrhagic complications, which occur in 20 % and 5-30 % of patients, respectively. The present report concerns a 38-year-old man, suffering from ET, who presented with two episodes of post-arthroscopic joint bleeding after synovectomy required for the treatment of synovial hypertrophy and chronic left knee joint synovitis. We discuss the current diagnostic approaches, as well as the risk factors predisposing to bleeding and its management, in patients with essential thrombocythemia.

Transient presence of clonal chromosomal aberrations in Ph-negative cells in patients with chronic myeloid leukemia remaining in deep molecular response on tyrosine kinase inhibitor treatment.

Advancements in treatment of chronic myeloid leukemia (CML) turned this formerly fatal neoplasm into a manageable chronic condition. Therapy with tyrosine kinase inhibitors (TKIs) often leads to significant reduction of disease burden, known as the deep molecular response (DMR). Herein, we decided to analyze the cohort of CML patients treated in our center with TKIs, who obtain and retain DMR for a period longer than 24 months. The aim of the study was to evaluate the frequency of clonal cytogenetic aberrations in Philadelphia-negative (Ph-) cells in patients with DMR during TKI treatment. The analyzed data was obtained during routine molecular and cytogenetic treatment monitoring, using G-banded trypsin and Giemsa stain (GTG) karyotyping and reverse transcription quantitative PCR. We noticed that approximately 50% of patients (28 of 55) in DMR had, at some follow-up point, transient changes in the karyotype of their Ph- bone marrow cells. In 9.1% of cases (5 of 55), the presence of the same aberrations was observed at different time points. The most frequently appearing aberrations were monosomies of chromosomes 19, 20, 21, and Y. Statistical analysis suggests that the occurrence of such abnormalities in CML patients correlates with the TKI treatment time.

The relationship between mean platelet volume and thrombosis recurrence in patients diagnosed with antiphospholipid syndrome.

Increased mean platelet volume (MPV) is associated with platelet reactivity and is a predictor of cardiovascular risk and unprovoked venous thromboembolism. The aim of our study was to evaluate MPV in patients with confirmed antiphospholipid antibody syndrome (APS) and to identify the correlation between the value of MPV and the recurrence of thrombosis. The studied group consists of 247 patients with a history of thrombosis and/or pregnancy loss (median age 38, range 18-66 years) classified as APS group (n = 70) or APS negative patients (n = 177) according to the updated Sapporo criteria. The control group consisted of 98 healthy subjects. MPV was significantly higher in the group of patients with clinically and laboratory confirmed APS (median 7.85, range 4.73-12.2 fl) in comparison with the controls. It was also higher than in APS negative patients (7.61, range 5.21-12.3 fl). APS patients with triple positivity for antiphospholipid antibodies with respect to Miyakis classification categories had higher MPV values than other APS patients (9.69 ± 1.85 vs. 7.29 ± 1.3 fl, p = 0.001). Recurrent thrombotic episodes were observed in 83 patients, but among the triple positive high-risk patients with APS in 80 % cases (p = 0.0046). In receiver operating characteristic curve analysis, the value of MPV level for thrombosis recurrence prediction in the APS group with sensitivity of 86 % and specificity of 82 % was 7.4 fl. In the multivariate logistic regression model, MPV above 7.4 fl (OR 3.65; 95 % CI 1.38-9.64, p = 0.009) significantly predicts thrombosis recurrence. Our results identify the value of MPV as a prognostic factor of thrombosis recurrence in patients with APS.

Bortezomib has little ex vivo activity in chronic myeloid leukemia: individual tumor response testing comparative study in acute and chronic myeloid leukemia.

AIM OF THE STUDY: Resistance to imatinib is one of the most important issues in treatment of chronic myeloid leukemia (CML) patients. The objective of the study was to analyze the ex vivo drug resistance profile to bortezomib and 22 other antileukemic drugs, including three tyrosine kinase inhibitors (TKIs), in CML in comparison to acute myeloid leukemia (AML). MATERIAL AND METHODS: A total of 82 patients entered the study, including 36 CML and 46 AML adults. Among CML patients, 19 had advanced disease, 16 were resistant to imatinib, and 6 had ABL-kinase domain mutations. The ex vivo drug resistance profile was studied by the MTT assay. RESULTS: CML CELLS WERE MORE RESISTANT THAN AML BLASTS TO THE FOLLOWING DRUGS: prednisolone, vincristine, doxorubicin, etoposide, melphalan, cytarabine, fludarabine, thiotepa, 4-HOO-cyclophosphamide, thioguanine, bortezomib, topotecan, and clofarabine. CML cells were 2-fold more sensitive to busulfan than AML cells. CML patients with clinical imatinib resistance had higher ex vivo resistance to vincristine, daunorubicin, etoposide, and busulfan. No significant differences to all tested drugs, including TKIs, were observed between CML patients with non-advanced and advanced disease. CML patients with mutation had higher ex vivo resistance to vincristine, idarubicin, thiotepa, and busulfan. CONCLUSIONS: CML cells are ex vivo more resistant to most drugs than acute myeloid leukemia blasts. Busulfan is more active in CML than AML cells. In comparison to AML cells, bortezomib has little ex vivo activity in CML cells. No differences between CML subgroups in sensitivity to 3 tested TKIs were detected.

Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.

INTRODUCTION: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment. OBJECTIVES: The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM). PATIENTS AND METHODS: Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months. The mean time of IM treatment was 18 months. At the time of the analysis, 75 patients were in the first chronic phase (CP), 4 in the second CP, 5 in the acceleration and 8 in the blastic phase. Fifty-seven patients (62%) were treated with IM at a daily dose of 400 mg and 35 patients with higher doses (600 or 800 mg daily). Inclusion criteria were based on the European Leukemia Net definitions for failure and suboptimal response to IM. RESULTS: Twelve mutations were detected in 11 of 92 patients, including 4 mutations (36.7%) diagnosed during CP, 3 (27.3%) in acceleration, and 4 (36.7%) in blast crisis. In 1 patient with lymphoid blast crisis of CML coexisting F359V and Y253F mutations were detected. In the whole group mutations were detected in 2 of 5 patients (40%) with primary resistance (M351T, F359V + Y253F) and in 9 of 87 patients (10.3%) (E255K, T315I-3x, M351T, E355G, F359V-2x) with acquired resistance to IM. CONCLUSIONS: The study confirmed the usefulness of BCR-ABL gene mutation screening in patients with CML resistant to IM therapy.

[Pulmonary embolism as a first manifestation of synchronous occurrence of two neoplasms]. / Zatorowosc plucna jako pierwszy objaw synchronicznego zachorowania na dwa nowotwory.

A case of 67-year-old man with a first episode of acute, unprovoked venous thromboembolism (VTE). Screening for cancer revealed coexistence of two neoplasms: colon sigmoid cancer (operated on 6 weeks after pulmonary embolism onset), and multiple myeloma (treated successfully with thalidomide and dexamethasone). Low molecular weight heparin use as VTE treatment was followed by thromboprophylaxis for myeloma therapy. During a 30-month follow-up period, neither new thromboembolic complications nor cancer recurrence were observed. Overlapping different prothrombotic mechanisms of double malignancy might result in detection of both neoplasms at early stage.