Tuberculosis is the deadliest infectious disease worldwide. Although the BCG vaccine is widely used, it does not efficiently protect against pulmonary tuberculosis and an improved tuberculosis ...vaccine is therefore urgently needed. Mycobacterium tuberculosis uses different ESX/Type VII secretion (T7S) systems to transport proteins important for virulence and host immune responses. We recently reported that secretion of T7S substrates belonging to the mycobacteria-specific Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins of the PGRS (polymorphic GC-rich sequences) and MPTR (major polymorphic tandem repeat) subfamilies required both a functional ESX-5 system and a functional PPE38/71 protein for secretion. Inactivation of ppe38/71 and the resulting loss of PE_PGRS/PPE-MPTR secretion were linked to increased virulence of M. tuberculosis strains. Here, we show that a predicted total of 89 PE_PGRS/PPE-MPTR surface proteins are not exported by certain animal-adapted strains of the M. tuberculosis complex including M. bovis. This Δppe38/71-associated secretion defect therefore also occurs in the M. bovis-derived tuberculosis vaccine BCG and could be partially restored by introduction of the M. tuberculosis ppe38-locus. Epitope mapping of the PPE-MPTR protein PPE10, further allowed us to monitor T-cell responses in splenocytes from BCG/M. tuberculosis immunized mice, confirming the dependence of PPE10-specific immune-induction on ESX-5/PPE38-mediated secretion. Restoration of PE_PGRS/PPE-MPTR secretion in recombinant BCG neither altered global antigenic presentation or activation of innate immune cells, nor protective efficacy in two different mouse vaccination-infection models. This unexpected finding stimulates a reassessment of the immunomodulatory properties of PE_PGRS/PPE-MPTR proteins, some of which are contained in vaccine formulations currently in clinical evaluation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Studies on surgical procedures in patients with concomitant primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have mainly been restricted to single centers. The aim ...was to compare surgical treatment of UC with or without PSC in a nationwide study.
Methods
A cohort study including all patients diagnosed with UC between 1987 and 2014 in Sweden was undertaken. The impact of PSC on the risk of colectomy, the chance of restorative surgery, and risk of failure (presence of a stoma) following restorative surgery were estimated. Survival analyses were performed using the Kaplan-Meier method and multivariable Cox regression models.
Results
Of 49 882 UC patients, 2079 had a PSC diagnosis at the end of follow-up. The risk of colectomy was unaffected by PSC diagnosis, whereas the chance of restorative surgery was elevated in PSC-UC patients (hazard ratio HR, 1.22; 95% confidence interval CI, 1.02-1.44). Ileorectal anastomosis (IRA) was performed in 63% of the PSC-UC patients and 43% of the non-PSC-UC-patients, and the corresponding numbers for ileal pouch anal anastomosis (IPAA) were 35% and 53%. There was no significantly increased risk of failure following restorative surgery in PSC patients (HR, 1.44; 95% CI, 0.93-2.22). In PSC-UC patients, the cumulative failure rates following an IRA at 3 and 5 years were 15% and 18%, and following an IPAA they were 11% and 18%, respectively.
Conclusions
Presence of PSC is not associated with the risk of colectomy, whereas the chance of restorative surgery in PSC-UC patients is higher than in UC alone.
Summary
Background
In young men, high body mass index (BMI) has been linked to liver disease later in life, but it is unclear if this also applies to women.
Aim
To study the association between BMI ...early in life and development of liver disease later in life in women.
Methods
We obtained data on early pregnancy BMI from 1 139 458 Swedish women between 1992 and 2015. National registers were used to ascertain incident severe liver disease, defined as cirrhosis, decompensated liver disease (hepatocellular carcinoma, oesophageal varices, hepatorenal syndrome or hepatic encephalopathy) or liver failure. A Cox regression model was used to investigate associations of BMI with incident severe liver disease adjusting for maternal age, calendar year, country of birth, smoking, civil status and education.
Results
During an average follow‐up of 13.8 years, 774 women developed severe liver disease. Compared to women with a low normal BMI (18.5‐22.4), an increased risk of severe liver disease was found in women with BMI between 22.5 and 24.9 kg/m2 (adjusted hazard ratio aHR 1.25, 95% CI 1.04‐1.50), 25.0 and 29.9 kg/m2 (aHR 1.27, 95% CI 1.05‐1.53) and BMI ≥ 30 kg/m2 (aHR 1.77, 95% CI 1.40‐2.24). When examining BMI as a continuous variable, the aHR increased by 4% per kg/m2 (95% CI 1.02‐1.05). A diagnosis of diabetes was associated with an increased risk of severe liver disease independent of baseline BMI.
Conclusion
A high BMI early in life in women is associated with a dose‐dependent, increased risk for future severe liver disease.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.
Methods
Candidate variables were assembled ...from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria.
Results
Based on data from 976 IIM patients (74% adults; 26% children) and 624 non‐IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) “probable IIM,” had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to “definite IIM.” A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50–<55% as “possible IIM.”
Conclusion
The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of “definite,” “probable,” and “possible” IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Construction companies followed either lower or higher business performance patterns.•Most companies presented lower patterns of occupational injuries overtime.•Low performing companies had a higher ...likelihood of experiencing high injury rates.•Labor-to-revenue ratio was associated with higher injury rates in all company sizes.
To identify patterns in business performance and occupational injuries (OIs) in the Swedish construction sector between 2003 and 2015 and investigate associations between these trajectories.
Company-level data were gathered from national registers. An open cohort of 13,089 private construction companies were classified by size. Yearly business performance indicators were return on equity, operating margin, and labor-to-revenue ratio. OIs rate was defined as number of injuries divided by number of employees. Group-based trajectory models were performed to identify companies with similar patterns in business performance and OIs rate over time. Associations were investigated with binomial regression models.
The model identified two main patterns (high/low) of injuries and business indicators for all company sizes. Trends in low labor-to-revenue ratio were associated with a high injury rate with a pooled estimate of 1.43 (95% CI 1.22–1.64) with some variation by company size: super small OR 1.3 (95% CI 1.01–1.62), small, OR 1.74 (95% CI 1.39–2.18), medium OR 1.3 (95% CI 0.9–1.8) and large OR 2.1 (95% CI 0.77–5.7). Similarly, low patterns of returns on equity were associated with high injury rate patterns across all company sizes, excluding small enterprises. No associations were found for operating margin patterns.
Low returns on equity and labor-to-revenue ratio were associated with higher OIs rate trajectories in the Swedish construction sector, which has implications for injury prevention as well as targeted surveillance and inspection. Further studies could investigate other economic sectors and possible mechanisms for this association.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to ...allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.
...we would like to emphasize that the introduction of a uniform gene nomenclature for other secretion systems in Gram-negative bacteria (type II, type III) has facilitated comparative analysis of ...these systems. Amongst the different topology prediction programs that were used (TMHMM Server v. 2.0, MEMSAT3, Philius, SCAMPI, HMMTOP and Phobius) MEMSAT3 gave the correct prediction for the highest number of Ecc membrane proteins. ...only the topology prediction results of TMHMM (used on the TubercuList server) and MEMSAT3 are shown.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
European consensus guidelines published in May 2013 recommended a target peripheral capillary oxygen saturation (SpO2) range of 90–95% for preterm infants. These were incorporated into guidelines ...at the Karolinska University Hospital, Sweden, in November 2013. This study compared clinical practice before and after those local guidelines.
Methods
We included infants who were born between 23 + 0 and 30 + 6 weeks from January 1, 2013 to December, 31 2015 and received intensive care in two Karolinska units. The lower saturation target of 88–92% and alarm limits of 85–95% used before November 2013 were compared to the new higher saturation target of 90–95% and alarm limits of 89–96%.
Results
Data from 399 infants were analysed. The mean SpO2 was 92.4% with the higher target (n = 301) and 91.1% with the lower target (n = 98). Using the higher instead of lower target meant that the SpO2 was within the prescribed target range more frequently (51% versus 30%) and the proportion of time with SpO2 >95% was increased by 9% (95% confidence interval 7–11%, p < 0.001).
Conclusion
The higher saturation target and tighter alarm limits led to higher mean oxygen saturation, increased adherence to the target and increased time with hyperoxaemia.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Many intensive care unit (ICU) patients describe pain and other adverse feelings that may impact long-term psychological morbidity. Sympathetically mediated palmar skin conductance variability is ...related to emotionally induced perspiration and correlates with pain levels in the perioperative setting but has not been studied in ICU patients.
Twenty non-intubated and 20 intubated general ICU patients were included in this observational study. Patients were monitored with the MED-STORM Pain Monitoring System®. The number of skin conductance fluctuations per second (NSCF) was measured in parallel with bedside observation during one hour of intensive care, including rest, procedures and patient-staff interactions. Arousal-agitation level was monitored with the motor activity assessment scale (MAAS). Pain was monitored with the numeric rating scale (0 to 10) in patients able to communicate or by observation in patients unable to communicate.
In non-intubated patients, NSCF increased with increasing stimulation/pain but also with higher MAAS (P=0.002). An interaction effect was found, with increased NSCF response to stimulation/pain with increasing MAAS (P<0.001).
In critically ill patients, NSCF may be more useful evaluating emotional distress rather than pain alone. It needs to be assessed whether NSCF monitoring is clinically useful and whether controlling emotional distress with the aid of such monitoring may impact on patient care and outcomes.
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