Initial steps towards developing a predictive algorithm of disease progression for hidradenitis suppurativa (HS): results from a Cox proportional hazard regression analysis on disease progression among a cohort of 335 Danish patients with HS.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory and scarring disease with a wide spectrum of disease severity. The amount of scarring is proportional to the preceding tissue damage and poses a challenge to patients. Severe HS is most often treatment recalcitrant, but hypothetically avoidable through early biologic treatment. Early prediction of individual risk of disease progression is therefore essential for patient management. OBJECTIVES: To investigate risk factors associated with disease progression and to design an algorithm capable of predicting disease -progression. METHODS: A prospective cohort study of 335 Hurley III-naïve patients with HS, not treated with biologics, was followed for a median of 2 years. Potential risk factors covered basic demographics, HS anamnestic factors and clinical HS factors collected during physical examination. Two separate Cox proportional hazard regression (CPHR) analyses were conducted. A summated 'progression score' was calculated and used in the predictive algorithm of severe disease. Subsequent bootstrap sampling was used to validate the predictability of the predictive algorithm. RESULTS: The CPHR analysis of Transition to severe disease found that active smoking [hazard ratio (HR) 4.01, 95% confidence interval (CI) 1.71-9.40, P = 0.001]; body mass index (BMI) points > 25 at baseline (each point: HR 1.06, 95% CI 1.02-1.09, P < 0.001); active disease in 2 (HR 4.26, 95% CI 1.23-14.84, P = 0.02) and ≥ 3 areas (HR 6.54, 95% CI 1.89-22.72, P = 0.003) all constituted substantial risk factors. Conversely, the CPHR analysis of Disease progression did not yield results of clinical relevance. A 'progression score' of 3.04 was used as a threshold in the predictive algorithm of Transition to severe disease and achieved the following test specifics: sensitivity = 0.51, specificity = 0.86, positive predictive value = 0.50, negative predictive value = 0.86. CONCLUSIONS: We found a disparity between factors increasing the risk of simple Disease progression and those increasing the risk of Transition to severe disease. For the latter, active smoking, BMI points > 25, active disease in 2 or ≥ 3 areas were all shown to be the clinically relevant factors that could be used to construct an algorithm that correctly predicted progression to severe HS in more than half of all instances.

Increased cancer incidence among patients with hidradenitis suppurativa - a Danish nationwide register study 1977-2017.

BACKGROUND: The chronic, inflammatory skin disease hidradenitis suppurativa (HS) (prevalence: 0.5%-1%, diagnostic delay: 7-10 years) primarily arises in younger adults and frequently coincides with autoimmune comorbidities and unhealthy life-styles (smoking and obesity). These factors are known to increase cancer risk, but despite this, information on cancer occurrence among HS patients is scarce. MATERIALS AND METHODS: A nationwide retrospective register-based study assessing relative risk of cancer - overall and by anatomical site - following HS diagnosis expressed as standardized incidence ratios (SIRs), which is ratios between observed cases among all Danes diagnosed with HS since 1977 and expected cases based on cancer incidence rates of the entire Danish population during the same period. RESULTS: Participants consisted of a cohort of 13,919 Danes with HS, who during an average of 14.2 years of follow-up developed a total of 1,193 incident cancers, corresponding to a 40% increased risk (SIR = 1.4, 95% CI: 1.3 to 1.4, p < 0.001). Increased risks were observed for cancers of the respiratory system, oral cavity and pharynx, digestive organs and peritoneum, urinary tract, and the lymphatic tissues. INTERPRETATION: These findings underline an unmet need for health monitoring, lifestyle interventions and cancer screening if and when relevant.

Heterozygosity for the Budapest 3 mutation in SERPINC1 in a family with thrombophilia and structural anomalies of the inferior vena cava.

BACKGROUND: Atresia of the infrarenal inferior vena cava (IVC) is associated with thrombophilia and antithrombin (AT) deficiency (ATD) due to homozygosity for the so-called Budapest 3 variant, c.391C > T, in the gene, SERPINC1. CASE PRESENTATION: We report on a father and his two sons that had severe thrombosis at a young age. One son had absence of, and the other had very gracile infrarenal IVC. The father had gracile vena iliaca. All had significant collateral building. AT activity was determined with four different methods and varied between moderately reduced and borderline normal values, depending on the method. While all were heterozygous for c.391C > T, the father was also heterozygous for a variant of uncertain significance in SERPINC1. CONCLUSIONS: The findings support the association between c.391C > T in SERPINC1, thrombophilia, and atresia of the IVC system and indicate that even heterozygosity for c.391C > T may contribute to such anomalies. ATD detection was hampered by the varying sensitivity of methods used for AT activity measurement.

The Global Hidradenitis Suppurativa Atlas Methodology: Combining Global Proportions in a Pooled Analysis.

INTRODUCTION: Data concerning the global burden of hidradenitis suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalences have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. METHODS: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital or a private/family medicine clinic. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Approximately ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). CONCLUSION: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation and synthesized using a random-effects model. The novel standardization of the Global Prevalence Studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies.

Benefits and Harms of Digital Health Interventions Promoting Physical Activity in People With Chronic Conditions: Systematic Review and Meta-Analysis.

BACKGROUND: Digital health interventions for managing chronic conditions have great potential. However, the benefits and harms are still unclear. OBJECTIVE: This systematic review and meta-analysis aimed to investigate the benefits and harms of digital health interventions in promoting physical activity in people with chronic conditions. METHODS: We searched the MEDLINE, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases from inception to October 2022. Eligible randomized controlled trials were included if they used a digital component in physical activity promotion in adults with ≥1 of the following conditions: depression or anxiety, ischemic heart disease or heart failure, chronic obstructive pulmonary disease, knee or hip osteoarthritis, hypertension, or type 2 diabetes. The primary outcomes were objectively measured physical activity and physical function (eg, walk or step tests). We used a random effects model (restricted maximum likelihood) for meta-analyses and meta-regression analyses to assess the impact of study-level covariates. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Of 14,078 hits, 130 randomized controlled trials were included. Compared with usual care or minimal intervention, digital health interventions increased objectively measured physical activity (end of intervention: standardized mean difference [SMD] 0.29, 95% CI 0.21-0.37; follow-up: SMD 0.17, 95% CI 0.04-0.31) and physical function (end of intervention: SMD 0.36, 95% CI 0.12-0.59; follow-up: SMD 0.29, 95% CI 0.01-0.57). The secondary outcomes also favored the digital health interventions for subjectively measured physical activity and physical function, depression, anxiety, and health-related quality of life at the end of the intervention but only subjectively measured physical activity at follow-up. The risk of nonserious adverse events, but not serious adverse events, was higher in the digital health interventions at the end of the intervention, but no difference was seen at follow-up. CONCLUSIONS: Digital health interventions improved physical activity and physical function across various chronic conditions. Effects on depression, anxiety, and health-related quality of life were only observed at the end of the intervention. The risk of nonserious adverse events is present during the intervention, which should be addressed. Future studies should focus on better reporting, comparing the effects of different digital health solutions, and investigating how intervention effects are sustained beyond the end of the intervention. TRIAL REGISTRATION: PROSPERO CRD42020189028; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=189028.

Physical activity after colorectal cancer surgery-a cross sectional study of patients with a long-term stoma.

PURPOSE: Physical activity is recommended to cancer survivors by the World Health Organisation (WHO) and is associated with improved survival after colorectal cancer. It remains unclear whether having a stoma is a barrier for an active lifestyle. We examined the level of physical activity and explored factors impacting physical activity in survivors with a stoma. METHODS: A total of 1265 (65%) patients in the Danish Stoma Database completed a multidimensional survey. Physical activity of moderate- and vigorous-intensity was assessed using two validated questions. Based on WHO guidelines, physical activity was categorised into 'Meeting' or 'Not Meeting' recommendations. Multivariate regression analysis, adjusting for potential confounders, provided odds ratio (OR) and 95% confidence intervals (CI) for factors' association with'Not Meeting' guideline recommendations. RESULTS: In total, 571 patients with colorectal cancer reported on physical activity at a median of 4.3 years (interquartile range 3.1-5.8) after stoma surgery. Two hundred ninety-three patients (51%) were 'Meeting recommendations' and 63% of them were 'Highly active'. Two hundred seventy-eight were 'Not meeting' recommendations (49%). Of the factors analysed, patients without support garment were more likely (OR 1.72 [95% CI 1.16; 2.54] not to meet guideline recommendations. We found no association between stoma type, surgical procedure, parastomal bulging and 'problematic stoma' and level of physical activity, respectively. CONCLUSION: In this large sample of survivors with a stoma half of patients met or exceeded guideline recommendations. Of patients not meeting recommendations some could potentially meet the recommendations by modest increases in either moderate or vigorous activity.

The Social and Psychological Impact of Acne Treatment: A Cross-Sectional Study of Blood Donors.

BACKGROUND: Acne in adolescence and adulthood is believed to have a long-term impact on socioeconomic status (SES) and health-related quality-of-life (HRQoL) in adults. OBJECTIVE: To estimate the cross-sectional prevalence of medically treated (MedTreAc) and untreated acne (UnTreAc) and to characterize its long-term impact in adults. METHODS: A nationwide cross-sectional study on 17 428 blood donors aged 18-35 was performed. Associations among acne and HRQoL, depressive symptoms, total income, and SES were investigated via linear/logistic/multinomial logistic regression analyses adjusted for relevant covariables. HRQoL was measured by the Short Form-12, and depressive symptoms by the Major Depression Inventory. The data were self-reported. RESULTS: Of the participants, 3591 (20.6%) and 1354 (7.8%) identified as the MedTreAc and UnTreAc phenotype, respectively. Neither phenotype was associated with a long-term impact on total income, but the MedTreAc group was associated with being an apprentice/student (OR = 1.26; 95% CI: 1.12, 1.42; P = 1.3×10-4) or high skill-level employee (OR = 1.22, 95% CI: 1.07; 1.39, P = .0023), while self-employment was more common for those with UnTreAc (OR = 1.53; 95% CI: 1.12, 2.06, P = .0061). Additionally, the UnTreAc group was associated with a lower mental HRQoL (SF-12 mental component summary score -1.05, 95% CI: -1.56, -0.54; P = 1.4×10-9) and increased odds ratio of depressive symptoms (OR = 1.44; 95% CI: 1.00, 2.02, P = .046). CONCLUSION: In this population of blood donors, the cumulative prevalence of MedTreAc and UnTreAc were 20.6% and 7.8%, respectively. Untreated acne had a long-term impact on psychosocial well-being in adulthood. It was associated with lower mental HRQoL and higher occurrence of depressive symptoms. Acne was not associated with a lower salary or SES.

Risk of Hidradenitis Suppurativa Comorbidities Over Time: A Prospective Cohort Study of Danish Blood Donors.

Hidradenitis suppurativa is a common recurrent inflammatory skin disease. It is associated with multiple comorbidities whose temporal relationships are unknown due to long diagnostic delays. This study of otherwise healthy blood donors with self-reported symptoms of hidradenitis suppurativa investigated the temporal relationships of comorbidities. A prospective survival analysis on a nationwide cohort of blood donors, using registry data on drug prescription, was used to calculate the hazard ratio of time until first prescription of medical treatment for the following hidradenitis suppurativa-related comorbidities: heart disease, diabetes, depression, thyroid disease and pain. Hidradenitis suppurativa status was determined by a validated questionnaire, and the survival analysis was adjusted for age, sex, body mass index, smoking status and having an International Classification of Diseases Version 10 (ICD-10) diagnosis of hidradenitis suppurativa. Of the participants, 1,012 reported hidradenitis suppurativa symptoms, and these symptoms increased the hazard ratio of antidepressants (1.73, 95% confidence interval 1.17-2.56, p ≈ 0.006) and analgesics (hazard ratio 1.24, 95% confidence interval 1.11-1.39, p < 0.001). Pain and depression are the first comorbidities to present in hidradenitis suppurativa pathogenesis.

Bacterial biofilm is associated with higher levels of regulatory T cells in unaffected hidradenitis suppurativa skin.

BACKGROUND: The role of bacterial biofilm in hidradenitis suppurativa (HS) is highly debated. Less biofilm is found in clinically unaffected axillary perilesional skin of HS patients compared with healthy controls. OBJECTIVE: To study the correlation between biofilm and the phenotypical characterization of the preclinical inflammatory infiltrate. MATERIALS AND METHODS: An exploratory comparative study of punch biopsies from unaffected axillary HS skin compared to similarly biopsies from healthy controls underwent standard staining procedures for CD4, CD8, CD25, FoxP3 and IL17. Standard-sized inflammatory histological hotspots were identified manually. Slides were scanned into Leica Biosystems' Digital Image Hub. Number of stained cells per slide and hotspot was found using an algorithm. RESULTS: 12.5% of HS had biofilm compared to 85% of controls. For full slides, HS patients had more CD4+ cells than controls; HS patients with biofilm had higher CD4+ cell number than controls with or without biofilm and HS patients without biofilm. For hotspots, HS patients with biofilm had higher number of CD4+FoxP3+ cells than HS patients without biofilm and controls with biofilm. CONCLUSION: The association between biofilm and the number of regulatory T cells in HS patients supports the concept of dysbiosis as a factor in the preclinical HS lesions.

The predictive value of coronary artery calcium detected by computed tomography in a prospective study on cardiac allograft vasculopathy in heart transplant patients.

The predictive value of coronary artery calcium (CAC) in heart transplant (HTX) patients is not established. We explored if the absence of CAC on computed tomography (CT) could exclude moderate and severe cardiac allograft vasculopathy [CAV2-3 ; the International Society for Heart and Lung Transplantation (ISHLT) recommended nomenclature] and significant coronary artery stenosis (diameter reduction ≥50%) and predict long-term clinical outcomes. HTX recipients (n = 133) were prospectively included and underwent CT for CAC scoring and invasive coronary angiography (ICA) 7.8 ± 5.0 years after HTX. CAC was detected in 73 (55%) patients. The absence of CAC on CT had a negative predictive value of 97% for ISHLT CAV2-3 and 88% for significant stenosis on ICA. During 7.5 ± 2.6 years of follow-up after CAC CT (n = 127), there were 57 (45%) nonfatal major adverse cardiac events and 23 (18%) deaths or graft losses registered as first events. Patients with CAC had significantly more events (P = 0.011). In an adjusted Cox regression analysis, the presence of CAC was significantly associated with a negative outcome (HR 1.8, 95% CI 1.1-3.0; P = 0.023). The absence of CAC predicted low prevalences of ISHLT CAV2-3 and significant coronary artery stenosis in HTX patients. The presence of CACS was significantly associated with a worse long-term outcome.

Coronary computed tomography in heart transplant patients: detection of significant stenosis and cardiac allograft vasculopathy, image quality, and radiation dose.

Background Cardiac allograft vasculopathy (CAV) is an accelerated form of atherosclerosis unique to heart transplant (HTX) patients. Purpose To investigate the detection of significant coronary artery stenosis and CAV, determinants of image quality, and the radiation dose in coronary computed tomography angiography (CCTA) of HTX patients with 64-slice multidetector CT (64-MDCT). Material and Methods Fifty-two HTX recipients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and underwent CCTA before ICA with intravascular ultrasound (IVUS). Results Interpretable CCTA images were acquired in 570 (95%) coronary artery segments ≥2 mm in diameter. Sensitivity, specificity, and positive and negative predictive values of CCTA for the detection of segments with significant stenosis (lumen reduction ≥50%) on ICA were 100%, 98%, 7.7%, and 100%, respectively. Twelve significant stenoses were located in segments with uninterpretable image quality or vessel diameter <2 mm; only one was eligible for intervention. IVUS detected CAV (maximal intimal thickness ≥0.5 mm) in 33/41 (81%) patients; CCTA and ICA identified CAV (any wall or luminal irregularity) in 18 (44%) and 14 (34%) of these 33 patients, respectively. The mean estimated radiation dose was 19.0 ± 3.4 mSv for CCTA and 5.7 ± 3.3 mSv for ICA ( P < 0.001). Conclusion CCTA with interpretable image quality had a high negative predictive value for ruling out significant stenoses suitable for intervention. The modest detection of CAV by CCTA implied a limited value in identifying subtle CAV. The high estimated radiation dose for 64-MDCT is of concern considering the need for repetitive examinations in the HTX population.

Serum Anticytokine Autoantibody Levels Are Not Increased in Hidradenitis Suppurativa: A Case-Control Pilot Study.

BACKGROUND: Hidradenitis suppurativa is a skin disease of recurrent episodes of inflammatory nodules, abscesses, and scarring of the intertriginous regions, e.g. the axillae and groin. A dysregulated immune response to one or more unknown antigens in hidradenitis suppurativa has been suggested. One hypothetical element of this dysregulation may be the functionality of the cytokines. This study examines the serum level of anticytokine autoantibodies for interleukin (IL)-1α, IL-6, IL-10, IL-17A, IL-17E, IL-17F, and interferon-α. METHOD: Recombinant, carrier-free cytokines were coupled to microspheres. The coupled beads were incubated for 1 h in the dark with assay buffer-diluted sera, and subsequently for 30 min with polyclonal goat F(ab')2 anti-human IgG phycoerythrin-conjugated antibody. Data are presented as the median fluorescence intensity of samples. RESULTS: No difference in levels of anticytokine autoantibodies was demonstrated for any of the autoantibodies studied. DISCUSSION: The data suggest that endogenously produced autoantibodies only play a minor role, if any, in hidradenitis suppurativa.

Structure of dimeric, recombinant Sulfolobus solfataricus phosphoribosyl diphosphate synthase: a bent dimer defining the adenine specificity of the substrate ATP.

The enzyme 5-phosphoribosyl-1-α-diphosphate (PRPP) synthase (EC 2.7.6.1) catalyses the Mg(2+)-dependent transfer of a diphosphoryl group from ATP to the C1 hydroxyl group of ribose 5-phosphate resulting in the production of PRPP and AMP. A nucleotide sequence specifying Sulfolobus solfataricus PRPP synthase was synthesised in vitro with optimised codon usage for expression in Escherichia coli. Following expression of the gene in E. coli PRPP synthase was purified by heat treatment and ammonium sulphate precipitation and the structure of S. solfataricus PRPP synthase was determined at 2.8 Å resolution. A bent dimer oligomerisation was revealed, which seems to be an abundant feature among PRPP synthases for defining the adenine specificity of the substrate ATP. Molecular replacement was used to determine the S. solfataricus PRPP synthase structure with a monomer subunit of Methanocaldococcus jannaschii PRPP synthase as a search model. The two amino acid sequences share 35 % identity. The resulting asymmetric unit consists of three separated dimers. The protein was co-crystallised in the presence of AMP and ribose 5-phosphate, but in the electron density map of the active site only AMP and a sulphate ion were observed. Sulphate ion, reminiscent of the ammonium sulphate precipitation step of the purification, seems to bind tightly and, therefore, presumably occupies and blocks the ribose 5-phosphate binding site. The activity of S. solfataricus PRPP synthase is independent of phosphate ion.

Light drives nitrogen fixation in tropical montane cloud forests in Costa Rica.

Tropical montane cloud forests are high altitude ecosystems characterized by very high ambient humidity, which favors organisms that depend on the environment for their water status, such as bryophytes and their nitrogen-fixing symbionts. Bryophyte-associated N2 fixation is a major source of new N in several northern environments, but their contributions to the N cycle in other ecosystems is still poorly understood. In this work, we evaluated N2 fixation rates associated with epiphytic bryophytes growing along the stems of pumpwood trees (Cecropia sp.) as well as in surrounding litter and soil from a primary and a secondary cloud forests in the Talamanca Mountain Range, Costa Rica. Nitrogen fixation was significantly higher in substrates from the secondary forest compared to those from the primary forest. Overall, N2 fixation rates associated with epiphytic bryophytes were 57 times those of litter and 270 times what was measured in soil. Further, light intensity was the major factor influencing N2 fixation rates in all substrates. Increased access to light in disturbed cloud forests may therefore favor bryophyte-associated N2 fixation, potentially contributing to the recovery of these ecosystems.

Hidradenitis suppurativa and female infertility: a pilot study conducted amongst 110 dermatological patients.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with severe consequences on quality of life. One aspect of this is that HS has been linked to an increased risk of infertility, but as data is still limited, it is not known if the association reflects causality. We performed a cross-sectional study of 161 female participants included at Zealand University Hospital, Roskilde, Denmark. Data regarding basic demographics, infertility, pregnancies, sexual function, and known factors with impact on fertility was collected. Logistic regressions were performed to analyze the association between HS and infertility, adjusting for factors that influence fertility. The study population consisted of 55 patients with HS, 55 patients with other dermatological diseases (ODD), and 51 healthy controls (HC). The HS group had a higher BMI, lower sexual function, and a higher tobacco use. We found no significant difference between the three groups in terms of whether they had children, the number of children they had, infertility, or whether they had received fertility treatments. The logistic analyses found no correlation between HS and infertility, and adjusting for factors affecting infertility did not alter this result. This study did not find a significant difference in infertility between patients with HS compared to those with ODD or HC. This result was not affected by adjustments for other factors known to influence fertility. Interestingly, the lower sexual function in the HS group did not appear to influence their desire or ability to conceive.

mHealth intervention including text messaging and behaviour change techniques to support maintenance of physical activity after cardiac rehabilitation: A single-arm feasibility study.

Objective: To evaluate the feasibility of a mobile health-supported intervention in patients with cardiovascular diseases after completion of a cardiac rehabilitation programme. Methods: The feasibility study was performed in two hospitals and one municipality in Region Zealand, Denmark. Eligible participants were ≥18 years old, participated in a supervised cardiac rehabilitation programme, had access to a mobile phone, and could walk 3 m independently. Participants received a 12-week intervention utilizing behaviour change techniques, consisting of action planning, text messages, and phone support. Feasibility was assessed using pre-defined progression criteria, which included recruitment (≥75%), retention (≥80%), accelerometer data completeness (≥80%), coordinator (phone support) time (≤30 min), the response rate on patient-reported outcomes (≥90%), adherence (≥75% respond to ≥75% of messages), and acceptability (≥75%). The secondary outcome of objective physical activity was assessed with accelerometers. Results: Ten women and 30 men with cardiovascular diseases aged 63.5 (±9.8 SD) participated. The progression criteria for retention (90%), accelerometer data completeness (83%), coordinator time (9.9 min), adherence (83%), and acceptability (82%) were at acceptable levels, exceptions were progression criteria for recruitment (35%) being below acceptable levels for recruitment, and response rate on patient-reported outcomes (75%). High satisfaction (92.6%) with the intervention was found. All objectively measured physical activity levels remained unchanged from baseline to follow-up. No serious adverse events related to the intervention were reported. Conclusion: Mobile health-supported maintenance of physical activity after cardiac rehabilitation completion was feasible, safe, and acceptable. Yet, changes to improve recruitment and response rate are needed before conducting a large-scale effect evaluation.