Predictors of Early Mortality Following Surgical or Non-surgical Treatment of Subaxial Cervical Spine Fractures: A Retrospective Nationwide Registry Study.

BACKGROUND: Traumatic subaxial cervical spine fractures are a significant public health concern due to their association with spinal cord injuries (SCI). Despite being mostly caused by low-energy trauma, these fractures significantly contribute to morbidity and mortality. Currently, research regarding early mortality based on the choice of treatment following these fractures is limited. Identifying predictors of early mortality may aid in postoperative patient monitoring and improve outcomes. PURPOSE: This study aimed to identify predictors of 30-days, 90-days, and one-year mortality in adults treated for subaxial fractures. STUDY DESIGN: A retrospective review of the nationwide Swedish Fracture Register (SFR). PATIENT SAMPLE: All adult patients in the SFR who underwent treatment for a subaxial cervical fracture (n = 1,963). OUTCOME MEASURES: Analyzed variables included age, sex, injury mechanism, neurological function, fracture characteristics, and treatment type. The primary endpoints were 30-days, 90-days, and one-year mortality. METHODS: 1,963 patients in the SFR, treated for subaxial cervical fractures between 2013 to 2021, were analyzed. Surgical procedures included anterior, posterior, or anteroposterior approaches. Non-surgical treatment included collar treatment or medical examinations without intervention. Stepwise regression and Cox regression analysis were used to determine predictors. Model performance was tested using the area under the receiver operating characteristic curve (AUC). RESULTS: 620 patients underwent surgery and 1,343 received non-surgical treatment. Surgical cases had primarily translation fractures, with 323 (52%) displaying no neurological deficits. Mortality rates at 30 days, 90 days, and one year were 22/620 (3.5%), 35/620 (5.6%), and 53/620 (8.5%), respectively. Age and SCI were predictors of mortality. Non-surgically treated patients mostly had compression fracture, with 1,214 (90%) experiencing no neurological deficits. Mortality rates at 30 days, 90 days, and one year were 41/1,343 (3.1%), 71/1,343 (5.3%), and 118/1,343 (8.7%). Age, male sex, SCI and fractures occurring at the C3 or C6 levels were predictors of mortality. An intact neurological function was a positive predictor of survival among non-surgically treated patients (AUC > 0.78). CONCLUSIONS: Age and SCI emerged as significant predictors of early mortality in both surgically and non-surgically treated patients. An intact neurological function served as a protective factor against early mortality in non-surgically treated patients. Fractures at C3 or C6 vertebrae may impact mortality.

CRISPR/Cas9-mediated gene disruption determines the roles of MITF and CITED2 in human mast cell differentiation.

The differentiation of hematopoietic stem and progenitor cells into the various cell lineages is regulated by cell-intrinsic factors and the progenitors' microenvironment. Experiments in mice have allowed the identification of transcriptional modulators that control mast cell differentiation. However, a comprehensive approach that allows efficient disruption of individual transcriptional modulators in primary human hematopoietic progenitors coupled with a mast cell formation readout has not been described. Here, we report a simple electroporation- and ribonucleoprotein-based knockout system that allows the identification of genes that are required and dispensable for human mast cell differentiation. We show that the transcription factor MITF is upregulated in human mast cell progenitors and reveal that the loss of MITF results in the suppressed formation of mast cells. By contrast, CITED2, another transcriptional modulator that is upregulated along the mast cell differentiation trajectory, was dispensable for human mast cell differentiation. Taken together, we report a CRISPR/Cas9-based framework that serves to identify genes involved in regulating the formation of human mast cells, and the results uncover the role of two transcriptional modulators in controlling human mast cell differentiation.

Plasma protein profiling to discern indolent from advanced systemic mastocytosis.

Mastocytosis is a heterogeneous disorder characterized by abnormal mast cell accumulation, in which the clinical severity may be explained by distinct molecular mechanisms. This study aimed to explore plasma protein biomarkers associated with systemic mastocytosis subtypes, as well as the cellular origin of the identified proteins. Plasma samples from patients with mastocytosis, including cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), advanced SM (AdvSM), and a reference group of patients with polycythemia vera (PCV), were analyzed by Proximity Extension Assay (OLINK technology) targeting 275 proteins. Furthermore, potential cellular origin was explored using an available scRNA sequencing data set generated from ISM patients. The study cohort included 16 patients with CM, 92 patients with SM (ISM, n=80; AdvSM, n=12), and 60 PCV patients. A Principal Component Analysis based on 275 plasma proteins revealed one cluster of CM and ISM patients that was separated from AdvSM patients. Up to 29 proteins were associated to distinct severe activity in SM patients (ISM vs AdvSM), including IL-1RT1, and TNFSF13B (q<0.01). Furthermore, scRNA seq analysis from ISM-derived bone marrow cells revealed that the mRNA for the identified proteins was not exclusive of mast cells. Distinct plasma protein profiles show potential to refine ISM and AdvSM diagnoses, possibly reflecting differences in pathogenic mechanisms and diverse clinical manifestations.

An optimized method for IgE-mediated degranulation of human lung mast cells.

Background: Mast cells are critically involved in IgE-mediated diseases, e.g., allergies and asthma. Human mast cells are heterogeneous, and mast cells from different anatomical sites have been shown to respond differently to certain stimuli and drugs. The origin of the mast cells is therefore of importance when setting up a model system, and human lung mast cells are highly relevant cells to study in the context of asthma. We therefore set out to optimize a protocol of IgE-mediated activation of human lung mast cells. Methods: Human lung mast cells were extracted from lung tissue obtained from patients undergoing pulmonary resection by enzyme digestion and mechanical disruption followed by CD117 magnetic-activated cell sorting (MACS) enrichment. Different culturing media and conditions for the IgE-mediated degranulation were tested to obtain an optimized method. Results: IgE crosslinking of human lung mast cells cultured in serum-free media gave a stronger response compared to cells cultured with 10% serum. The addition of stem cell factor (SCF) did not enhance the degranulation. However, when the cells were put in fresh serum-free media 30 minutes prior to the addition of anti-IgE antibodies, the cells responded more vigorously. Maximum degranulation was reached 10 minutes after the addition of anti-IgE. Both CD63 and CD164 were identified as stable markers for the detection of degranulated mast cells over time, while the staining with anti-CD107a and avidin started to decline 10 minutes after activation. The levels of CD203c and CD13 did not change in activated cells and therefore cannot be used as degranulation markers of human lung mast cells. Conclusions: For an optimal degranulation response, human lung mast cells should be cultured and activated in serum-free media. With this method, a very strong and consistent degranulation response with a low donor-to-donor variation is obtained. Therefore, this model is useful for further investigations of IgE-mediated mast cell activation and exploring drugs that target human lung mast cells, for instance, in the context of asthma.

Long-term outcomes after surgery for subaxial cervical spine injuries in octogenarians, a matched population-based cohort study.

PURPOSE: We aimed to investigate surgical outcomes in octogenarians with subaxial cervical spine injuries and determine the predictors of complications and mortality. METHODS: Eligible for inclusion were all patients surgically treated between 2006 and 2018, with either anterior or posterior fixation for subaxial spine injuries. A cohort of octogenarians was identified and matched 1:1 to a corresponding cohort of younger adults. Primary outcomes were perioperative complications and mortality. RESULTS: Fifty-four patients were included in each of the octogenarian and younger groups (median age: 84.0 vs. 38.5). While the risks for surgical complications, including dural tears and wound infections, were similar between groups, the risks of postoperative medical complications, including respiratory or urinary tract infections, were significantly higher among the elderly (p < 0.05). Additionally, there were no differences in operative time (p = 0.625) or estimated blood loss (p = 0.403) between groups. The 30 and 90-day mortality rates were significantly higher among the elderly (p = 0.004 and p < 0.001). These differences were due to comorbidities in the octogenarian cohort as they were revoked when propensity score matching was performed to account for the differences in American Society of Anesthesiology (ASA) grade. Multivariable logistic regression revealed age and ASA score to be independent predictors of complications and the 90-day mortality, respectively. CONCLUSIONS: Octogenarians with comorbidities were more susceptible to postoperative complications, explaining the increased short-term mortality in this group. However, octogenarians without comorbidities had similar outcomes compared to the younger patients, indicating that overall health, including comorbidities, rather than chronological age should be considered in surgical decision-making.

Predictors of failure after primary anterior cervical discectomy and fusion for subaxial traumatic spine injuries.

INTRODUCTION: Traumatic subaxial fractures account for more than half of all cervical spine injuries. The optimal surgical approach is a matter of debate and may include anterior, posterior or a combined anteroposterior (360º) approach. Analyzing a cohort of patients initially treated with anterior cervical discectomy and fusion (ACDF) for traumatic subaxial injuries, the study aimed to identify predictors for treatment failure and the subsequent need for supplementary posterior fusion (PF). METHODS: A retrospective, single center, consecutive cohort study of all adult patients undergoing primary ACDF for traumatic subaxial cervical spine fractures between 2006 and 2018 was undertaken and 341 patients were included. Baseline clinical and radiological data for all included patients were analyzed and 11 cases of supplementary posterior fixation were identified. RESULTS: Patients were operated at a median of 2.0 days from the trauma, undergoing 1-level (78%), 2-levels (16%) and ≥ 3-levels (6.2%) ACDF. A delayed supplementary PF was performed in 11 cases, due to ACDF failure. On univariable regression analysis, older age (p = 0.017), shorter stature (p = 0.031), posterior longitudinal ligament (PLL) injury (p = 0.004), injury to ligamentum flavum (p = 0.005), bilateral facet joint dislocation (p < 0.001) and traumatic cervical spondylolisthesis (p = 0.003) predicted ACDF failure. On the multivariable regression model, older age (p = 0.015), PLL injury (p = 0.048), and bilateral facet joint dislocation (p = 0.010) remained as independent predictors of ACDF failure. CONCLUSIONS: ACDF is safe and effective for the treatment of subaxial cervical spine fractures. High age, bilateral facet joint dislocation and traumatic PLL disruption are independent predictors of failure. We suggest increased vigilance regarding these cases.

Effectiveness of integrated person-centered interventions for older people's care: Review of Swedish experiences and experts' perspective.

Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers' scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field.

Patients' expectations of primary health care from both patients' and physicians' perspectives: a questionnaire study with a qualitative approach.

BACKGROUND: Patients' ideas, concerns, and expectations are three important concepts in consultation techniques. Limited studies on these concepts include responses from both health care providers and care recipients of the same consultation. Highlighting both perspectives provides an increased understanding of the consultation. This study aims to explore the perspectives of patients and health care professionals about patients' expectations of primary health care during consultations with primary care physicians and compare the two sets of perspectives. METHODS: A cross-sectional study. Patients (n = 113) and physicians (n = 67) from five primary health care centers completed a questionnaire after planned consultations. Their responses to open-ended questions about patients' expectations, from patients' and physicians' perspectives were analyzed with qualitative content analyses. RESULTS: The patients expected a personal journey, through the primary health care system where they were the subject of interest. A journey, with ready access to a health care provider followed by a consultation with the physician, medical measures administered, their outcomes discussed, and a plan developed for continued health care. The physicians observed patients' expectations to concern the responsibilities placed on primary health care where patients were the object of interest. Patients' short-term expectations were described in a similar way by both patients and physicians. Patients expressed their long-term expectations as more personal and interpersonal whereas physicians observed them from a more professional and organizational standpoint. CONCLUSIONS: Patients and physicians have different views of what patients expect of primary health care. While patients' short-term expectations were perceived by physicians, their long-term expectations were not. Patients expected more of a personal journey through the primary health care system while physicians observed patients' expectations to concern the responsibilities placed on primary health care. Identifying and meeting patients' expectations is an important part of patient-centered care, and a better understanding of patients' expectations is needed to improve health professionals' consultation skills.

Epidemiology of mastocytosis: a population-based study (Sweden).

BACKGROUND: Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator-related symptoms and is divided into systemic mastocytosis (SM) and cutaneous mastocytosis (CM). The epidemiology of mastocytosis remains incompletely understood. OBJECTIVE: To estimate the incidence, prevalence, overall survival (OS) and burden of comorbidities in adult mastocytosis patients identified in Swedish population-based registries. METHODS: Individuals (≥ 20 years of age) with a mastocytosis diagnosis in the National Patient Register (NPR) and/or the Swedish Cancer Register (SCR) between 2001 and 2018, were identified. In a matched cohort design, for each case five randomly selected mastocytosis-free comparators matched on age, sex, and county of residence were chosen from the Population Register. The Kaplan-Meier method was used to compare OS between individuals with mastocytosis and comparators. Information on concomitant disease at baseline was assessed by use of the Charlson Comorbidity Index (CCI). RESULTS: We identified 2,040 adults with a mastocytosis diagnosis yielding an annual incidence of 1.56 per 100,000 (95% CI 1.29-1.87) and a prevalence of 23.9 per 100,000 (95% CI 22.8-25.0). The comorbidity burden was higher, and the OS lower, in patients with mastocytosis compared to comparators. INTERPRETATION: We found a higher incidence and prevalence of mastocytosis compared to assessments in other settings and confirmed that the prognosis generally is favorable. Of special note was evidence of a higher comorbidity burden in mastocytosis patients compared to the background population. LIMITATIONS: Underreporting and inconsistencies in the use of diagnostic codes.

Dysphagia, health-related quality of life, and return to work after occipitocervical fixation.

PURPOSE: The purpose of this study was to evaluate patient-reported outcome measures (PROMS) on dysphagia, health-related quality of life (HRQoL) and return to work after occipitocervical fixation (OCF). Postoperative radiographic measurements were evaluated to identify possible predictors of dysphagia. METHODS: All individuals (≥ 18 years) who underwent an OCF at the study center or were registered in the Swedish spine registry (Swespine) between 2005 and 2019, and were still alive when the study was conducted, were eligible for inclusion. There was no overlap between the cohorts. Prospectively collected data on dysphagia (Dysphagia Short Questionnaire DSQ), HRQoL (EQ5D-3L) and return to work were used. Radiological and baseline patient data were retrospectively collected. In addition, HRQoL data of a matched sample of individuals was elicited from the Stockholm Public Health Survey 2006. RESULTS: In total, 54 individuals were included. At long-term follow-up, 26 individuals (51%) had no dysphagia, and 25 (49%) reported some degree of dysphagia: 11 (22%) had mild dysphagia, and 14 (27%) had moderate to severe dysphagia. On a group level, the OCF sample scored significantly lower EQVAS and EQ-5Dindex values compared to the general population (60.0 vs. 80.0, p = 0.016; 0.43 vs. 0.80, p < 0.001). Individuals working preoperatively returned to work after surgery. Of those responding, 88% stated that they would undergo the OCF operation if it was offered today. No predictors of dysphagia based on radiographic measurements were identified. CONCLUSION: Occipitocervical fixation results in a high frequency of long-term dysphagia. The HRQoL of OCF patients is significantly reduced compared to matched controls. However, most patients are satisfied with their surgery. No radiographic predictors of long-term dysphagia could be identified. Future prospective and systematic studies with larger samples and more objective outcome measures are needed to elucidate the causes of dysphagia in OCF.

A comparative trial of blood pressure monitoring in a self-care kiosk, in office, and with ambulatory blood pressure monitoring.

BACKGROUND: Automated measurement of blood pressure (BP) in designated BP kiosks have in recent years been introduced in primary care. If kiosk blood pressure (BP) monitoring provides results equivalent to in-office BP or daytime ambulatory BP monitoring (ABPM), follow-up of adult patients could be managed primarily by self-checks. We therefore designed a comparative trial and evaluated the diagnostic performance of kiosk- and office-based BP (nurse- versus physician-measured) compared with daytime ABPM. METHODS: A trial of automated BP monitoring in three settings: a designated BP kiosk, by nurses and physicians in clinic, and by ABPM. The primary outcome was systolic and diastolic BP, with respective diagnostic thresholds of ≥135 mmHg and/or ≥ 85 mmHg for daytime ABPM and kiosk BP and ≥ 140 mmHg and/or ≥ 90 mmHg for office BP (nurse- and physician-measured). RESULTS: Compared with daytime ABPM, mean systolic kiosk BP was higher by 6.2 mmHg (95% confidence interval [CI] 3.8-8.6) and diastolic by 7.9 mmHg (95% CI 6.2-9.6; p < 0.001). Mean systolic BP taken by nurses was similar to daytime ABPM values (+ 2.0 mmHg; 95% CI - 0.2-4.2; p = 0.071), but nurse-measured diastolic values were higher, by 7.2 mmHg (95% CI 5.9-9.6; p < 0.001). Mean systolic and diastolic physician-measured BPs were higher compared with daytime ABPM (systolic, by 7.6 mmHg [95% CI 4.5-10.2] and diastolic by 5.8 mmHg [95% CI 4.1-7.6]; p < 0.001). Receiver operating characteristic curves of BP monitoring across pairs of systolic/diastolic cut-off levels among the three settings, with daytime ABPM as reference, demonstrated overall similar diagnostic performance between kiosk and nurse-measured values and over the curve performance for physician-measured BP. Accuracy with nurse-measured BP was 69.2% (95% CI 60.0-77.4%), compared with 65.8% (95% CI 56.5-74.3%) for kiosk BP. CONCLUSIONS: In this study kiosk BP monitoring was not comparable to daytime ABPM but could be an alternative to in-office BP monitoring by trained nurses. The diagnostic performance of kiosk and nurse-measured BP monitoring was similar and better than that of physician-measured BP. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04488289) 27/07/2020.

Medical students' perception of learning from patient encounters in primary health care; a qualitative interview study.

BACKGROUND: Clinical practice gives medical students opportunities to develop clinical skills and to gain insight into their future profession as a physician. Students in the medical programme at Karolinska Institutet in Sweden had clinical practice in primary health care in nine of their 11 semesters. The aim of this study was to explore medical students' perceptions of learning from patient encounters in a primary health care context. METHODS: The study was a qualitative inductive interview study. The 21 participating medical students were from their 3rd, 4th and 5th (final year) year of the study programme. A semi-structured interview guide was used. The data analysis was performed with qualitative content analysis. RESULTS: The overarching theme of the study was: The individual patient encounters are the key to learning in primary health care. The patient encounters presented both useful opportunities and challenges that could contribute to the students' professional development. The following four categories were found: 1. Patient encounters in are instructive, rewarding and challenging. Practising in primary health care provided experience in meeting and communicating with a wide variety of patients. Students described it being challenging to trust in their own clinical competence and feeling a responsibility towards the patients. 2. Encounters with patients in primary health care provide opportunities for gradual professional development. Students had the opportunity of increasing independence based on their level of clinical competence. They experienced a progression in their professional development after each period in primary health care. 3. A committed supervisor plays a significant role in learning. Committed supervisors who set aside time for supervision, offered support, and encouraged the student, played an important role in the student's learning. 4. Learning in primary health care and learning in hospitals complement one another. It could be difficult for the students to sort out exactly where they learnt different things as they perceived that learning in primary health care and in hospitals complemented one another. CONCLUSIONS: The students' encounters with authentic patients in primary health care gave them recurring opportunities to develop communication skills and to be trusted to work on their own under supervision, giving them guidance on their way to becoming future physicians.

Make My Day: primary prevention of stroke using engaging everyday activities as a mediator of sustainable health - a randomised controlled trial and process evaluation protocol.

INTRODUCTION: The individual, societal and economic benefits of stroke prevention are high. Even though most risk factors can be reduced by changes to lifestyle habits, maintaining new and healthy activity patterns has been shown to be challenging.The aim of the study is to evaluate the impact of an interdisciplinary team-based, mHealth-supported prevention intervention on persons at risk for stroke. The intervention is mediated by engaging everyday activities that promote health. An additional aim is to describe a process evaluation that serves to increase knowledge about how the programme leads to potential change by studying the implementation process and mechanisms of impact. METHODS AND ANALYSIS: The study will be a randomised controlled trial including 104 persons at risk for stroke. Persons at risk of stroke (n=52) will be randomised to an mHealth-supported stroke prevention programme. Controls will have ordinary primary healthcare (PHC) services. The 10-week programme will be conducted at PHC clinics, combining group meetings and online resources to support self-management of lifestyle change using engaging everyday activities as a mediator. Primary outcomes are stroke risk, lifestyle habits and participation in health-promoting activities. Assessments will be performed at baseline and at follow-up (11 weeks and 12 months). The effects of the programme will be analysed using inferential statistics. Implementation will be analysed using qualitative and quantitative methods. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority. Study results will be disseminated in peer-reviewed journals and at regional and international conferences targeting mixed audiences. TRIAL REGISTRATION NUMBER: NCT05279508.

The impact of residency training in family medicine on hospital admissions due to Ambulatory-care Sensitive Conditions in Rio de Janeiro.

Lack of skilled human resources in primary care remains a major concern for policymakers in low- and middle-income countries. There is little evidence supporting the impact of residency training in family medicine in the quality of care, and it perpetuates misconceptions among policymakers that the provision of primary care can be easily done by any physician without special training. This article compares the risk of patients being hospitalized due to Ambulatory care sensitive conditions and the odds of having follow-up visits in primary care after hospital discharge, according to the type of their medical provider: (1) Generalists (reference), (2) Family physicians; and, (3) patients with no consultations prior to the event. Multilevel multivariate binomial regression models estimated the relative risks of a patient being hospitalized in a given month and the relative risks for the occurrence of a follow-up visit in primary care in a retrospective cohort of 636.640 patients between January 2013 and July 2018 in Rio de Janeiro. For all 14 conditions, there was a higher risk of hospitalization when patients had no consultation in primary care prior to the event. Except for Ear, Nose and Throat infections, patients seen by family physicians had a lower risk of being hospitalized, compared to patients seen by Generalists. Follow-up visits were more likely to happen among patients treated by family physicians for almost every condition analyzed. With two years of training in family medicine, Family physicians can reduce the risk of their patients being hospitalized and increase the likelihood of those patients having a follow-up consultation in primary care. Investments in residency training in family medicine should be made to fix the shortage of skilled physicians in primary care, reduce hospitalizations and improve quality and continuity of care.

Hypertension management in primary health care: a survey in eight regions of Sweden.

PURPOSE: To explore hypertension management in primary healthcare (PHC). DESIGN: Structured interviews of randomly selected PHC centres (PHCCs) from December 2019 to January 2021. SETTING: Seventy-six PHCCs in eight regions of Sweden. MAIN OUTCOME MEASURES: Staffing and organization of hypertension care. Methods of measuring blood pressure (BP), laboratory tests, registration of co-morbidities and lifestyle advice at diagnosis and follow-up. RESULTS: The management of hypertension varied among PHCCs. At diagnosis, most PHCCs (75%) used the sitting position at measurements, and only 13% routinely measured standing BP. One in three (33%) PHCCs never used home BP measurements and 25% only used manual measurements. The frequencies of laboratory analyses at diagnosis were similar in the PHCCs. At follow-up, fewer analyses were performed and the tests of lipids and microalbuminuria decreased from 95% to 45% (p < 0.001) and 61% to 43% (p = 0.001), respectively. Only one out of 76 PHCCs did not measure kidney function at routine follow-ups. Lifestyle, physical activity, food habits, smoking and alcohol use were assessed in ≥96% of patients at diagnosis. At follow-up, however, there were fewer assessments. Half of the PHCCs reported dedicated teams for hypertension, 82% of which were managed by nurses. There was a great inequality in the number of patients per tenured GP in the PHCCs (median 2500; range 1300-11300) patients. CONCLUSIONS: The management of hypertension varies in many respects between PHCCs in Sweden. This might lead to inequity in the care of patients with hypertension.

Hypertension is mainly handled in primary healthcare (PHC), and this study shows important dissimilarities in organization and clinical management.Several variants in techniques and measurements of blood pressure were found between PHC centres.Lifestyle, clinical and laboratory assessments decreased at follow-ups compared to at diagnosis, specifically for lipids, microalbuminuria and electrocardiograms.Nearly half of the PHC centres reported that they had dedicated hypertension teams.

Analysis of human lung mast cells by single cell RNA sequencing.

Mast cells are tissue-resident cells playing major roles in homeostasis and disease conditions. Lung mast cells are particularly important in airway inflammatory diseases such as asthma. Human mast cells are classically divided into the subsets MCT and MCTC, where MCT express the mast cell protease tryptase and MCTC in addition express chymase, carboxypeptidase A3 (CPA3) and cathepsin G. Apart from the disctintion of the MCT and MCTC subsets, little is known about the heterogeniety of human lung mast cells and a deep analysis of their heterogeniety has previously not been performed. We therefore performed single cell RNA sequencing on sorted human lung mast cells using SmartSeq2. The mast cells showed high expression of classical mast cell markers. The expression of several individual genes varied considerably among the cells, however, no subpopulations were detected by unbiased clustering. Variable genes included the protease-encoding transcripts CMA1 (chymase) and CTSG (cathepsin G). Human lung mast cells are predominantly of the MCT subset and consistent with this, the expression of CMA1 was only detectable in a small proportion of the cells, and correlated moderately to CTSG. However, in contrast to established data for the protein, CPA3 mRNA was high in all cells and the correlation of CPA3 to CMA1 was weak.

European Competence Network on Mastocytosis (ECNM): 20-Year Jubilee, Updates, and Future Perspectives.

In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve diagnosis and management of patients with mast cell (MC) disorders. The ECNM consists of a net of specialized centers, expert physicians, and scientists who dedicate their work to MC diseases. One essential aim of the ECNM is to timely distribute all available information about the disease to patients, doctors, and scientists. In the past 20 years, the ECNM has expanded substantially and contributed successfully to the development of new diagnostic concepts, and to the classification, prognostication, and treatments of patients with mastocytosis and MC activation disorders. The ECNM also organized annual meetings and several working conferences, thereby supporting the development of the World Health Organization classification between 2002 and 2022. In addition, the ECNM established a robust and rapidly expanding patient registry and supported the development of new prognostic scoring systems and new treatment approaches. In all projects, ECNM representatives collaborated closely with their U.S. colleagues, various patient organizations, and other scientific networks. Finally, ECNM members have started several collaborations with industrial partners, leading to the preclinical development and clinical testing of KIT-targeting drugs in systemic mastocytosis, and some of these drugs received licensing approval in recent years. All these networking activities and collaborations have strengthened the ECNM and supported our efforts to increase awareness of MC disorders and to improve diagnosis, prognostication, and therapy in patients.

House Dust Mite and Cat Dander Extract Induce Asthma-Like Histopathology with an Increase of Mucosal Mast Cells in a Guinea Pig Model.

Background: Asthma is a chronic inflammatory disease with structural changes in the lungs defined as airway remodelling. Mast cell responses are important in asthma as they, upon activation, release mediators inducing bronchoconstriction, inflammatory cell recruitment, and often remodelling of the airways. As guinea pigs exhibit anatomical, physiological, and pharmacological features resembling human airways, including mast cell distribution and mediator release, we evaluated the effect of extracts from two common allergens, house dust mite (HDM) and cat dander (CDE), on histopathological changes and the composition of tryptase- and chymase-positive mast cells in the guinea pig lungs. Methods: Guinea pigs were exposed intranasally to HDM or CDE for 4, 8, and 12 weeks, and airway histology was examined at each time point. Hematoxylin and eosin, Picro-Sirius Red, and Periodic Acid-Schiff staining were performed to evaluate airway inflammation, collagen deposition, and mucus-producing cells. In addition, Astra blue and immunostaining against tryptase and chymase were used to visualize mast cells. Results: Repetitive administration of HDM or CDE led to the accumulation of inflammatory cells into the proximal and distal airways as well as increased airway smooth muscle mass. HDM exposure caused subepithelial collagen deposition and mucus cell hyperplasia at all three time points, whereas CDE exposure only caused these effects at 8 and 12 weeks. Both HDM and CDE induced a substantial increase in mast cells after 8 and 12 weeks of challenges. This increase was primarily due to mast cells expressing tryptase, but not chymase, thus indicating mucosal mast cells. Conclusions: We here show that exposure to HDM and CDE elicits asthma-like histopathology in guinea pigs with infiltration of inflammatory cells, airway remodelling, and accumulation of primarily mucosal mast cells. The results together encourage the use of HDM and CDE allergens for the stimulation of a clinically relevant asthma model in guinea pigs.