Örebro University Hospital

Ludvigsson J.F.

The coronavirus disease 2019 (COVID‐19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare.

Simon T.G., Roelstraete B., Khalili H., Hagström H., Ludvigsson J.F.

ObjectivePopulation-based data are lacking regarding the risk of overall and cause-specific mortality across the complete histological spectrum of non-alcoholic fatty liver disease (NAFLD).DesignThis nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD (1966 to 2017; n=10 568). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden’s 28 pathology departments, after excluding other etiologies of liver disease, and further categorised as, simple steatosis, non-fibrotic steatohepatitis (NASH), non-cirrhotic fibrosis and cirrhosis. NAFLD cases were matched to ≤5 general population comparators by age, sex, calendar year and county (n=49 925). Using Cox regression, we estimated multivariable-adjusted HRs (aHRs) and 95% CIs.ResultsOver a median of 14.2 years, 4,338 NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (16.9 vs 28.6/1000 PY; difference=11.7/1000 PY; aHR=1.93, 95% CI=1.86 to 2.00). Compared with controls, significant excess mortality risk was observed with simple steatosis (8.3/1000 PY, aHR=1.71, 95% CI=1.64 to 1.79), non-fibrotic NASH (13.4/1000 PY, aHR=2.14, 95% CI=1.93 to 2.38), non-cirrhotic fibrosis (18.4/1000 PY, aHR=2.44, 95% CI=2.22 to 2.69) and cirrhosis (53.6/1000 PY, aHR=3.79, 95% CI=3.34 to 4.30)(ptrend <0.01). This dose-dependent gradient was similar when simple steatosis was the reference (ptrend <0.01). The excess mortality associated with NAFLD was primarily from extrahepatic cancer (4.5/1000 PY, aHR=2.16, 95% CI=2.03 to 2.30), followed by cirrhosis (2.7/1000 PY, aHR=18.15, 95% CI=14.78 to 22.30), cardiovascular disease (1.4/1000 PY, aHR=1.35, 95% CI=1.26 to 1.44) and hepatocellular carcinoma (HCC) (1.2/1000 PY, aHR=11.12, 95% CI=8.65 to 14.30).ConclusionAll NAFLD histological stages were associated with significantly increased overall mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.

Zhang H., Ahearn T.U., Lecarpentier J., Barnes D., Beesley J., Qi G., Jiang X., O’Mara T.A., Zhao N., Bolla M.K., Dunning A.M., Dennis J., Wang Q., Ful Z.A., Aittomäki K., et. al.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1–3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10−8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores. Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

Ludvigsson J.F.

Aim Persistent symptoms in adults after COVID-19 are emerging and the term long COVID is increasingly appearing in the literature. However, paediatric data are scarce. Methods This paper contains a case report of five Swedish children and the long-term symptoms reported by their parents. It also includes a systematic literature review of the MEDLINE, EMBASE and Web of Science databases and the medRxiv/bioRxiv pre-print servers up to 2 November 2020. Results The five children with potential long COVID had a median age of 12 years (range 9–15) and four were girls. They had symptoms for 6–8 months after their clinical diagnoses of COVID-19. None were hospitalised at diagnosis, but one was later admitted for peri-myocarditis. All five children had fatigue, dyspnoea, heart palpitations or chest pain, and four had headaches, difficulties concentrating, muscle weakness, dizziness and sore throats. Some had improved after 6–8 months, but they all suffered from fatigue and none had fully returned to school. The systematic review identified 179 publications and 19 of these were deemed relevant and read in detail. None contained any information on long COVID in children. Conclusion Children may experience similar long COVID symptoms to adults and females may be more affected.

Debono B., Wainwright T.W., Wang M.Y., Sigmundsson F.G., Yang M.M., Smid-Nanninga H., Bonnal A., Le Huec J., Fawcett W.J., Ljungqvist O., Lonjon G., de Boer H.D.

AbstractBackground Enhanced Recovery After Surgery (ERAS) evidence-based protocols for perioperative care have led to improvements in outcomes in numerous surgical areas, through multimodal optimization of patient pathway, reduction of complications, improved patient experience and reduction in the length of stay. ERAS represent a relatively new paradigm in spine surgery. Purpose This multidisciplinary consensus review summarizes the literature and proposes recommendations for the perioperative care of patients undergoing lumbar fusion surgery with an ERAS program. Study Design This is a review article. Methods Under the impetus of the ERAS® society, a multidisciplinary guideline development group was constituted by bringing together international experts involved in the practice of ERAS and spine surgery. This group identified 22 ERAS items for lumbar fusion. A systematic search in the English language was performed in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Systematic reviews, randomized controlled trials, and cohort studies were included, and the evidence was graded according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Consensus recommendation was reached by the group after a critical appraisal of the literature. Results Two hundred fifty-six articles were included to develop the consensus statements for 22 ERAS items; one ERAS item (prehabilitation) was excluded from the final summary due to very poor quality and conflicting evidence in lumbar spinal fusion. From these remaining 21 ERAS items, 28 recommendations were included. All recommendations on ERAS protocol items are based on the best available evidence. These included nine preoperative, eleven intraoperative, and six postoperative recommendations. They span topics from preoperative patient education and nutritional evaluation, intraoperative anesthetic and surgical techniques, and postoperative multimodal analgesic strategies. The level of evidence for the use of each recommendation is presented. Conclusion Based on the best evidence available for each ERAS item within the multidisciplinary perioperative care pathways, the ERAS® Society presents this comprehensive consensus review for perioperative care in lumbar fusion.

Duffy S.W., Tabár L., Yen A.M., Dean P.B., Smith R.A., Jonsson H., Törnberg S., Chen S.L., Chiu S.Y., Fann J.C., Ku M.M., Wu W.Y., Hsu C., Chen Y., Svane G., et. al.

Background It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done b ...

Janier M., Unemo M., Dupin N., Tiplica G.S., Potočnik M., Patel R.

The 2020 edition of the European guideline on the management of syphilis is an update of the 2014 edition. Main modifications and updates include: -The ongoing epidemics of early syphilis in Europe, particularly in men who have sex with men (MSM) -The development of dual treponemal and non-treponemal point-of-care (POC) tests -The progress in non-treponemal test (NTT) automatization -The regular episodic shortage of benzathine penicillin G (BPG) in some European countries -The exclusion of azithromycin as an alternative treatment at any stage of syphilis -The pre-exposure or immediate post-exposure prophylaxis with doxycycline in populations at high risk of acquiring syphilis.

Ludvigsson J.F.

Aim COVID-19 has affected millions of people worldwide. This paper reviews the Swedish pandemic response. Methods A narrative review was carried out and a timeline constructed. Results By September 1, 2020, 0.8% of Swedish residents had tested positive for the virus and 0.06% of the population had died, which was higher than neighbouring Nordic countries, but lower than some European countries with general lockdowns. The main actors were the Public Health Agency, the National Board of Health and Welfare, the Civil Contingencies Agency and the Government. County councils and regions implemented policies, in conjunction with the Department of Education and county administrative boards. Sweden's response was less invasive than many other countries, with no general lockdown. It focused on mitigation: slowing, but not stopping, the pandemic. Physical distancing was recommended in public spaces, but mandatory in bars, restaurants and at events. Visits to nursing facilities were banned. Kindergartens and schools for children up to 16 stayed open, but closed for older children for three months. There were no enforced quarantines for infected households or geographical regions, and facemasks were not recommended outside health care. Conclusion Sweden chose a different pandemic strategy to its peer nations. This paper examines the first eight months.

Ludvigsson J.F.

Many countries have closed schools and kindergartens to minimise COVID-19, but the role that children play in disease transmission is unclear.A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID-19 transmission by children.We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID-19 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID-19 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS-COV-2 virus, which causes COVID-19, and even asymptomatic children can have viral loads.Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID-19 mortality rates in older people.

Miyata T., Ueda Y., Shinzato T., Iida Y., Tanaka S., Kurokawa K., van Ypersele de Strihou C., Maeda K.

Pentosidine is an advanced glycation end product and its formation is shown to be closely related to oxidative processes. Recent studies have shown that pentosidine levels are increased not only in plasma and matrix proteins from diabetic patients, but also markedly in nondiabetic hemodialysis patients. Currently, the mechanism of accumulation and kinetics of pentosidine formation in hemodialysis patients remain unknown. Gel filtration of uremic plasma revealed that plasma pentosidine exists in the albumin fraction (approximately 90%) and, interestingly, in free form (approximately 5%) as well. Plasma free pentosidine was undetectable in subjects with normal renal function. There was a significant correlation between the plasma levels of albumin-linked and free pentosidine in hemodialysis patients. Kinetic studies indicated that dietary pentosidine was absorbed into the circulation and that, after either oral or intravenous administration of pentosidine to intact or nephrectomized rats, the plasma free pentosidine level was closely linked to the level of renal function. These findings demonstrate that: (1) Pentosidine accumulates as albumin-linked and in free form in the circulation of uremic patients; (2) dietary pentosidine can be absorbed into the circulation, thus being one possible origin of circulating free pentosidine; (3) free pentosidine may accumulate as a result of decreased glomerular filtration; and (4) the mechanism of accumulation of albumin-linked pentosidine is not related to high glucose levels. It suggests the simultaneous accumulation, during renal failure, of either unknown pentosidine precursor(s) or catalyst(s) of glycoxidation, independent of glucose.