Surgical strategy in lithium-associated hyperparathyroidism: A population-based study.

BACKGROUND: The extent of parathyroidectomy (PTX) recommendation in patients with lithium-associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long-term outcomes. METHODS: A population-based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non-LAH). RESULTS: Lithium exposure was significantly more common among PHPT (n = 202, 2.3%) than in controls (n = 416, 0.5%); OR 5.0 (95% CI 4.2-5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH-group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re-admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5 years duration of lithium exposure prior to surgery. CONCLUSIONS: The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence.

Regional variations in the management of primary hyperparathyroidism in Sweden: population-based case-control study.

BACKGROUND: Substantial disparities in the utilization of parathyroidectomy for primary hyperparathyroidism have been reported. This study aimed to analyse regional variations in parathyroidectomy incidence with respect to the patient's disease burden and socioeconomic status. METHODS: A population-based case-control study included all patients with primary hyperparathyroidism who underwent parathyroidectomy in Sweden between 2008 and 2017 and 10 matched controls. Data on demographic and socioeconomic variables, co-morbidities and drug prescriptions were collected from relevant national registers. Conditional logistic regression was used to analyse predictors of parathyroidectomy. RESULTS: A total of 8626 patients with primary hyperparathyroidism (77% women) underwent parathyroidectomy during the study interval. The annual incidence of parathyroidectomy was 9.0 per 100 000 persons. The annual age-adjusted regional incidences of parathyroidectomy varied between 3.3 and 16.9 operations per 100 000 inhabitants. Except for a small underrepresentation of patients with lower education, no effect of socioeconomic variables was observed. Compared with matched controls, the parathyroidectomy group had increased odds ratios of having developed classical symptoms of primary hyperparathyroidism and being prescribed medication against cardiovascular disorders and psychiatric illness at the time of parathyroidectomy. Increased risks of kidney stones and osteoporosis were observed 5 years before parathyroidectomy. Patients with primary hyperparathyroidism selected for parathyroidectomy from regions with a low incidence of operations had a higher prevalence of kidney stones, osteoporosis and hypertension, as well as larger adenomas and higher calcium levels at the time of parathyroidectomy compared with patients in high-incidence regions. CONCLUSION: The considerable variation in parathyroidectomy seems more likely associated with different clinical thresholds for detection of primary hyperparathyroidism and referral to surgery than socioeconomic disparities.

Risk of pre-eclampsia and impact of disease activity and antirheumatic treatment in women with rheumatoid arthritis, axial spondylarthritis and psoriatic arthritis: a collaborative matched cohort study from Sweden and Denmark.

OBJECTIVE: To explore the risk of pre-eclampsia in rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA), focusing on the impact of treatment and disease activity. METHODS: We identified RA, AxSpA and PsA singleton pregnancies (2006-2018) by linking medical birth registers to Swedish (SRQ) and Danish (DANBIO) rheumatology registers. Control pregnancies from the medical birth registers were matched 1:10 on maternal age, parity and birth year.We obtained information on antirheumatic treatment before and during pregnancy and disease activity during pregnancy. Risks of pre-eclampsia in RA, AxSpA and PsA pregnancies, compared with control pregnancies, were estimated overall and by antirheumatic treatment (conventional synthetic disease-modifying antirheumatic drug (DMARD)/biological DMARD/corticosteroids, as monotherapy or combination therapy) and disease load (Health Assessment Questionnaire≥1/C-reactive protein≥10/Disease Activity Score in 28 joints≥3.2) through logistic regression (adjusted ORs (aORs) with 95% CI). RESULTS: We observed 69, 34, and 26 pre-eclampsia events among RA (n=1739), AxSpA (n=819) and PsA (n=489), resulting in a risk of pre-eclampsia of, respectively, aOR 1.27 (95% CI 0.96 to 1.67), 1.17 (0.76 to 1.78) and 1.85 (1.10 to 3.12), compared with controls.For RA, maternal combination therapy before and during pregnancy was associated with increased risk (1.59; 1.07 to 2.37 and 1.53; 0.97 to 2.39, respectively). For PsA, maternal monotherapy before pregnancy was associated with pre-eclampsia (2.72; 1.4 to 5.13). In RA pregnancies with available information (43%), high disease load was associated with doubled risk of pre-eclampsia (aOR 1.96; 1.26 to 3.04). CONCLUSION: PsA pregnancies, but not AxSpA pregnancies, were at increased risk of pre-eclampsia. For RA, combination therapy (potentially a surrogate for high disease activity both before and during pregnancy) and high disease load during pregnancy might be a risk factor for pre-eclampsia.

The Neuroimmune Response to Surgery - An Exploratory Study of Trauma-Induced Changes in Innate Immunity and Heart Rate Variability.

Surgery triggers a systemic inflammatory response that ultimately impacts the brain and associates with long-term cognitive impairment. Adequate regulation of this immune surge is pivotal for a successful surgical recovery. We explored the temporal immune response in a surgical cohort and its associations with neuroimmune regulatory pathways and cognition, in keeping with the growing body of evidence pointing towards the brain as a regulator of peripheral inflammation. Brain-to-immune communication acts through cellular, humoral and neural pathways. In this context, the vagal nerve and the cholinergic anti-inflammatory pathway (CAP) have been shown to modify peripheral immune cell activity in both acute and chronic inflammatory conditions. However, the relevance of neuroimmune regulatory mechanisms following a surgical trauma is not yet elucidated. Twenty-five male patients undergoing elective laparoscopic abdominal surgery were included in this observational prospective study. Serial blood samples with extensive immune characterization, assessments of heart rate variability (HRV) and cognitive tests were performed before surgery and continuing up to 6 months post-surgery. Temporal immune responses revealed biphasic reaction patterns with most pronounced changes at 5 hours after skin incision and 14 days following surgery. Estimations of cardiac vagal nerve activity through HRV recordings revealed great individual variations depending on the pre-operative HRV baseline. A principal component analysis displayed distinct differences in systemic inflammatory biomarker trajectories primarily based on pre-operative HRV, with potiential consequences for long-term surgical outcomes. In conclusion, individual pre-operative HRV generates differential response patterns that associate with distinct inflammatory trajectories following surgery. Long-term surgical outcomes need to be examined further in larger studies with mixed gender cohorts.

Neuropsychiatric Comorbidity in Primary Hyperparathyroidism Before and After Parathyroidectomy: A Population Study.

BACKGROUND: Primary hyperparathyroidism (PHPT) is often accompanied by neuropsychiatric symptoms. This study aimed to map out psychiatric comorbidity as reflected by medical treatment for psychiatric symptoms. METHODS: A retrospective case-control analysis and a prospective cohort analysis of psychotropic drug utilization before and after PTX. A total of 8279 PHPT patients treated with parathyroidectomy in Sweden between July 1, 2008 and December 31, 2017 compared to a matched control cohort from the total population (n = 82,790). Information on filled prescriptions was collected from the Swedish Prescribed Drug Register (SDR). Socioeconomic data and diagnoses were added by linkage to national patient and population registers. Regression analyses were used to calculate relative drug utilization (OR) within 3 years prior to PTX and relative incidence of drug treatment (RR) within 3 years postoperatively. RESULTS: Utilization of antidepressant, anxiolytic and sleep medication was more comprehensive in PHPT patients compared with the controls prior to PTX. The most common were benzodiazepines [OR 1.40 (95% CI: 1.31-1.50)] and selective serotonin reuptake inhibitors [SSRI; OR 1.38 (95% CI: 1.30-1.47)]. Postoperatively, the excess prescription rate for anxiolytic benzodiazepines decreased within three years from a 30 to 19% excess and for benzodiazepines for sleep from 31 to 14%. No corresponding decrease in excess prescription rate was observed for SSRI. CONCLUSION: PHPT is associated with increased utilization of antidepressive medications and benzodiazepines before PTX. This study implies that psychiatric symptoms should be considered in PHPT patients and continuous medication should be reevaluated after PTX.

Pregnancy Outcomes in Women With Psoriatic Arthritis in Relation to Presence and Timing of Antirheumatic Treatment.

OBJECTIVE: To evaluate pregnancy outcomes in relation to antirheumatic treatment before and during pregnancy, as a proxy of disease severity in pregnant women with psoriatic arthritis (PsA), compared to those without PsA. METHODS: Our study focused on a Swedish nationwide registry-based cohort study that included 921 PsA pregnancies and 9,210 non-PsA pregnancies occurring between 2007 and 2017 (matched 1:10 based on maternal age, year of delivery, and parity). We estimated adjusted odds ratios (ORs) overall, with 95% confidence intervals (95% CIs), and stratified by presence, timing, and type of antirheumatic treatment. Adjustments were made for maternal body mass index, smoking, education level, and country of birth. The outcome of preterm birth was also stratified by parity. RESULTS: Pregnant women with PsA versus those without PsA were more obese, more often smokers, and more frequently had a diagnosis of pregestational hypertension and diabetes mellitus. Increased risks in PsA pregnancies versus non-PsA pregnancies were primarily preterm birth (adjusted OR 1.69 [95% CI 1.27-2.24]) and cesarean delivery (adjusted OR 1.77 [95% CI 1.43-2.20] for elective delivery, and adjusted OR 1.42 [95% CI 1.10-1.84] for emergency delivery). The risks differed according to the presence, timing, and type of antirheumatic treatment, with the most increased risk in PsA pregnancies (versus non-PsA) occurring with antirheumatic treatment during pregnancy (adjusted OR 2.30 [95% CI 1.49-3.56] for preterm birth). The corresponding adjusted OR for preterm birth in women with PsA who were exposed specifically to biologic treatment during pregnancy was 4.49 [95% CI 2.60-7.79]. Risk of preterm birth was primarily increased in first pregnancies. CONCLUSION: Compared to non-PsA pregnancies, risks of preterm birth and cesarean delivery were mostly increased in those exposed to antirheumatic treatment during pregnancy, especially biologic treatments. As parity influences the risk of preterm birth in women with PsA, special attention to first pregnancies is warranted. Women with PsA should receive individualized monitoring during pregnancy.

Implant Attributes or Patient Characteristics? Factors Affecting Outcome after Breast Augmentation in Transgender Women.

Implant-based breast augmentation is a valuable tool for treatment of gender dysphoria in transgender women. The aim was to assess whether implant attributes, plane selection, and patient characteristics had an impact on the surgical outcome, and to compare these parameters between transgender and cisgender breast augmentations. Methods: A cohort of transgender women who underwent breast augmentation at our department during 2009-2018 were retrospectively studied. The cohort was also compared with a cohort of 12,884 mainly cisgender women registered in the Swedish breast implant registry (BRIMP) during 2014-2019. Results: A total of 143 transgender individuals were included, with a median follow-up of 5.7 years. Complications occurred in 20 patients (14.0%), four patients (2.8%) underwent acute reoperation, and 20 patients (14.0%) had secondary corrections. No differences were seen in complication rates when comparing prepectoral with subpectoral placement (15.1% versus 12.9%; P = 0.81); size, less than 400 mL versus greater than or equal to 400 mL (14.7% versus 13.3%; P = 0.81), or the shape of the implants, round versus anatomic (10.7% versus 22.2%; P = 0.10). In comparison with the cohort from BRIMP, the transgender cohort had more round implants (72.0% versus 60.7%; P < 0.01), larger implants (44.1% had volumes of 400-599 mL, compared with 25.4%; P < 0.0001), and more prepectoral placement (51.0% versus 7.3%; P < 0.0001). The risk of reoperation less than 30 days was 1.2% in BRIMP and 2.8% in the transgender cohort (P = 0.08). Conclusions: In transgender women, implants are often larger, round, and placed prepectoral' compared with cisgender women. Despite these differences, complication rates were equivalent. Implant attributes, surgical techniques, and patient characteristics were not independently associated with the rate of complications.

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

BACKGROUND: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses. METHODS: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020. RESULTS: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses. CONCLUSIONS: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

Improved Surgical Outcome with Double Incision and Free Nipple Graft in Gender Confirmation Mastectomy.

BACKGROUND: Mastectomy and chest-wall contouring is the most common gender confirmation surgery. With increasing prevalence of transgender individuals, there is a demand for better surgical outcomes and aesthetic results. Our aim was to evaluate surgical techniques used and assess modifications in gender confirmation mastectomies at Karolinska University hospital in Stockholm, Sweden. METHODS: A retrospective cohort study was performed on 464 patients undergoing gender confirmation mastectomies in our department between 2009 and 2018. Patient demographics, psychiatric comorbidity, surgical method, and outcome were analyzed. Follow-up was at least one year. RESULTS: The most frequently used surgical technique for gender confirmation mastectomies was double incision with free nipple graft (243 patients, 52.4%), followed by periareolar incision (113 patients, 24.4%) and semicircular incision (67 patients, 14.4%). The double incision technique and periareolar technique were associated with 18.9% and 28.3% complications, 3.3% and 12.4% acute reoperations, 28.4% and 65.5% secondary revisions, respectively. The double incision technique increased from being used in 17.8% of all mastectomies during 2009-2013 to 62.9% during 2014-2018, while periareolar incision decreased from 43.0% to 18.5%. CONCLUSIONS: The current study describes a successful transition of surgical technique from periareolar incision to double incision with free nipple graft in gender confirmation mastectomy, leading to significant improvements in the overall outcome with fewer complications, less acute reoperations and less secondary corrections. Hence, we consider the double incision with free nipple graft technique to be the favored technique in the vast majority of cases in female-to-male chest wall contouring.

Intraoperative Hypotension and Myocardial Infarction Development Among High-Risk Patients Undergoing Noncardiac Surgery: A Nested Case-Control Study.

BACKGROUND: Hemodynamic instability during anesthesia and surgery is common and associated with cardiac morbidity and mortality. Information is needed regarding optimal blood pressure (BP) threshold in the perioperative period. Therefore, the effect of intraoperative hypotension (IOH) on risk of perioperative myocardial infarction (MI) was explored. METHODS: A nested case-control study with patients developing MI <30 days postsurgery matched with non-MI patients, sampled from a large surgery cohort. Study participants were adults undergoing noncardiac surgery at 3 university hospitals in Sweden, 2007-2014. Matching criteria were age, sex, American Society of Anesthesiologists (ASA) physical status, cardiovascular disease, hospital, year-, type-, and extent of surgery. Medical records were reviewed to validate MI diagnoses and retrieve information on comorbid history, baseline BP, laboratory and intraoperative data. Main exposure was IOH, defined as a decrease in systolic blood pressure (SBP), in mm Hg, from preoperative individual resting baseline lasting at least 5 minutes. Outcomes were acute MI, fulfilling the universal criteria, subclassified as type 1 and 2, occurring within 30 days and mortality beyond 30 days among case and control patients. Conditional logistic regression assessed the association between IOH, decrease in SBP from individual baseline, and perioperative MI. Mortality rates were estimated using Cox proportional hazards. Relative risk estimates are reported as are the corresponding absolute risks derived from the well-characterized source population. RESULTS: A total of 326 cases met the inclusion criteria and were successfully matched with 326 controls. The distribution of MI type was 59 (18%) type 1 and 267 (82%) type 2. Median time to MI diagnosis was 2 days; 75% were detected within a week of surgery. Multivariable analysis acknowledged IOH as an independent risk factor of perioperative MI. IOH, with reduction of 41-50 mm Hg, from individual baseline SBP, was associated with a more than tripled increased odds, odds ratio (OR) = 3.42 (95% confidence interval [CI], 1.13-10.3), and a hypotensive event >50 mm Hg with considerably increased odds in respect to MI risk, OR = 22.6, (95% CI, 7.69-66.2). In patients with a very high-risk burden, the absolute risk of an MI diagnosis increased from 3.6 to 68 per 1000 surgeries. CONCLUSIONS: In patients undergoing noncardiac surgery, IOH is a possible contributor to clinically significant perioperative MI. The high absolute MI risk associated with IOH, among a growing population of patients with a high-risk burden, suggests that increased vigilance of BP control in these patients may be beneficial.

Oncological outcomes after complete mesocolic excision in right-sided colon cancer: a population-based study.

AIM: Complete mesocolic excision (CME) has been proposed as the preferred surgical technique for resection of colon cancer. This prospective cohort study evaluates the effect of CME surgery on colon cancer mortality after right-sided hemicolectomy on a population level. METHODS: Data from the Swedish Colorectal Cancer Registry and the Cause of Death Registry on all patients treated with elective right-sided hemicolectomy for colon cancer Stages I-III in the Stockholm County 2008-2012 were analysed. Adherence to principles of CME surgery was determined by structured analysis of anonymized surgical reports regarding the presence of five essential features. The exposure to CME was graded as group 0 (not exposed to CME), group 1 (intermediate) and group 2 (exposed to CME). RESULTS: In total, 1171 patients were analysed with 234 (20.0%) patients in CME group 0, 453 (38.7%) patients in CME group 1 and 484 (41.3%) in CME group 2. The 5-year colon cancer mortality was 20.2% in CME group 0, 13.9% in CME group 1 and 13.1% in CME group 2 (P = 0.026). The adjusted hazard ratio for colon cancer mortality was 0.61 (95% CI 0.42-0.91; P = 0.014) for CME group 1 and 0.52 (95% CI 0.35-0.77; P = 0.001) for CME group 2. DISCUSSION: The presence of predefined CME features in surgical reports was related to a graded benefit on cancer-specific mortality after right-sided hemicolectomy for colon cancer Stages I-III.

Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.

BACKGROUND: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function. METHODS: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid ß (Aß1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery. RESULTS: CSF and blood concentrations of T-tau, neurone-specific enolase, and Aß1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aß1-42. CONCLUSIONS: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.

Malaria and risk of lymphoid neoplasms and other cancer: a nationwide population-based cohort study.

BACKGROUND: Malaria is associated with Burkitt lymphoma among children in Sub-Saharan Africa. No longitudinal studies have assessed the long-term risk of other lymphoma or cancer overall. Here, we investigated the risk of lymphoid neoplasms and other cancer after malaria. METHODS: We included 4125 patients diagnosed with malaria in Sweden in 1987-2015, identified either through the National Surveillance Database at the Public Health Agency of Sweden, the National Inpatient and Outpatient Register, or by reports from microbiology departments. A comparator cohort (N = 66,997) matched on sex, age and birth region was retrieved from the general population and an additional cohort with all individuals born in Sub-Saharan Africa registered in the Total Population Register in 1987-2015 (N = 171,756). Incident lymphomas and other cancers were identified through linkage with the Swedish Cancer Register. Hazard ratios (HRs) were assessed using Cox regression with attained age as the timescale. RESULTS: A total of 20 lymphoid neoplasms and 202 non-haematological cancers were identified among malaria patients during a mean follow-up of 13.3 and 13.7 years, respectively. The overall risk of lymphoid neoplasms was not significantly increased (hazard ratio [HR] 1.24, 95% confidence interval [CI] 0.79-1.94), neither did we find any association with all-site non-haematological cancer (HR 0.89, 95% CI 0.77-1.02). However, in the Sub-Saharan Africa cohort, we observed an increased risk of lymphoid neoplasms after malaria diagnosis (HR 2.39, 95% CI 1.06-5.40), but no difference in the risk of other cancer (HR 1.01, 95% CI 0.70-1.45). The association could not be explained by co-infection with HIV or chronic hepatitis B or C, since the risk estimate was largely unchanged after excluding patients with these comorbidities (HR 2.63, 95% CI 1.08-6.42). The risk became more pronounced when restricting analyses to only including non-Hodgkin and Hodgkin lymphomas (HR 3.49, 95% CI 1.42-8.56). CONCLUSION: Individuals born in malaria-endemic areas and diagnosed with malaria in Sweden had an increased risk of lymphoid neoplasms, especially B cell lymphoma. There was no association with cancer overall nor did single malaria episodes confer an increased risk in travellers.

Sarcoma of the breast: breast cancer history as etiologic and prognostic factor-A population-based case-control study.

PURPOSE: Sarcomas of the breast account for about 1% of all breast malignancies. The aim of this national survey was to explore etiologic and prognostic factors. METHODS: Utilizing national Swedish registers, all patients registered with mesenchymal tumors in the breast during the period 1993-2013 (n = 344) were identified and compared to up to ten age and gender matched controls. Cancer history was retrieved for cases and controls. Conditional Poisson regression models were used for calculation of odds ratios. RESULTS: Previous breast cancer was overrepresented among patients with angiosarcoma. The highest risk occurred ≥ 5 years after treatment for breast cancer (OR 73.9, 95% confidence interval, CI, 25.4-215; P < 0.001). An increase in incidence of angiosarcoma was observed during the study period (1.10, 95% CI 1.05-1.16; P < 0.001). The overall incidence of breast sarcoma increased from 1.52 to 2.04 cases per million per year. Angiosarcoma of the breast was associated with a significant excess mortality compared to age-matched controls (HR 4.65, 95% CI 3.01-7.19; P < 0.001). CONCLUSIONS: Angiosarcoma increased in incidence and displayed a more severe clinical course, with significantly shorter survival. The strong association between a history of breast cancer 5 years or more prior to the diagnosis of angiosarcoma points to radiotherapy as a contributing factor.

Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy.

BACKGROUND: Most anti-tumour necrosis factor (anti-TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections. AIMS: To assess the risk of paediatric infections after maternal anti-TNF treatment. METHODS: Population-based cohort study in Denmark, Finland and Sweden 2006-2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti-TNF, and 9346 children to women with non-biologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years. RESULTS: Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23-1.67) for anti-TNF and 1.14 (1.07-1.21) for non-biologic systemic treatment, and 1.29 (1.11-1.50) and 1.09 (1.02-1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti-TNF, 1.19 (1.11-1.29), and for non-biologic systemic treatment, 1.10 (1.07-1.13). There was no difference among anti-TNF agents, treatment in the third trimester, or between mono/combination therapy with non-biologic systemic treatment. CONCLUSIONS: Both anti-TNF and non-biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, or with combination treatment, and were not persistent during the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare-seeking behaviour. This may in turn shift the risk-benefit equation towards continuation of treatment even in the third trimester.

Myocardial infarction after noncardiac surgery in Sweden: a national, retrospective observational cohort study.

BACKGROUND: The precise incidence of perioperative myocardial infarction (MI) after noncardiac surgery remains unclear. We determined the incidence and risk factors for perioperative MI after noncardiac surgery and the risk of MI and mortality compared with matched non-surgical patients. METHODS: Patients >18 yr undergoing noncardiac surgery in 23 Swedish hospitals from 2007 to 2014 were included in this national observational retrospective cohort study. We combined national surgical and outcome databases with Swedeheart, a national quality registry capturing data from patients with acute MI. The primary outcome was incidence of MI within 30 days of surgery. Multivariable logistic regression identified preoperative risk factors associated with MI, including ASA grade, diabetes mellitus, and cardiovascular pathology including previous MI. Standardised incidence rate ratios were calculated. Mortality rates were estimated using Cox proportional hazards. RESULTS: A total of 1605/400 742 (0.41%) patients (median age: 64 [49-75] yr) had an MI after surgery, which was independently associated with increasing age, comorbidities and higher risk (vascular, thoracic), emergency surgery, or all. The incidence of perioperative MI (per 1000 surgeries) varied from 0.064 (95% confidence interval [CI], 0.02-012) in low-risk patients (ASA physical status 1) to 15.8 (95% CI, 14.9-16.8) among higher risk patients (ASA physical status ≥3, age ≥80 yr, high-risk surgery). Perioperative MI was associated with higher 30-day mortality (adjusted odds ratio: 5.49 [95% 4.76-6.32]). Compared with the non-surgical Swedish population, the perioperative standardised incidence rate ratio was five-fold higher (odds ratio: 5.35 [95% CI: 5.09-5.61]). CONCLUSIONS: In a large Swedish surgical cohort, the incidence of MI within 30 days of noncardiac surgery was 0.41%, chiefly occurring in a small subset of higher risk patients.

Anti-TNF treatment during pregnancy and birth outcomes: A population-based study from Denmark, Finland, and Sweden.

PURPOSE: To study the risk of preterm birth, caesarean section, and small for gestational age after anti-tumor necrosis factor agent treatment (anti-TNF) in pregnancy. METHODS: Population-based study including women with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, and their infants born 2006 to 2013 from the national health registers in Denmark, Finland, and Sweden. Women treated with anti-TNF were compared with women with nonbiologic systemic treatment. Adalimumab, etanercept, and infliximab were compared pairwise. Continuation of treatment in early pregnancy was compared with discontinuation. Odds ratios with 95% confidence intervals were calculated in logistic regression models adjusted for country and maternal characteristics. RESULTS: Among 1 633 909 births, 1027 infants were to women treated with anti-TNF and 9399 to women with nonbiologic systemic treatment. Compared with non-biologic systemic treatment, women with anti-TNF treatment had a higher risk of preterm birth, odds ratio 1.61 (1.29-2.02) and caesarean section, 1.57 (1.35-1.82). The odds ratio for small for gestational age was 1.36 (0.96-1.92). In pairwise comparisons, infliximab was associated with a higher risk of severely small for gestational age for inflammatory joint and skin diseases but not for inflammatory bowel disease. Discontinuation of anti-TNF had opposite effects on preterm birth for inflammatory bowel disease and inflammatory joint and skin diseases. CONCLUSIONS: Anti-TNF agents were associated with increased risks of preterm birth, caesarean section, and small for gestational age. However, the diverse findings across disease groups may indicate an association related to the underlying disease activity, rather than to agent-specific effects.

Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study.

OBJECTIVE: Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. METHODS: Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. RESULTS: Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). INTERPRETATION: Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. Ann Neurol 2020;87:370-382.

Risk of adverse birth outcomes after maternal varenicline use: A population-based observational study in Denmark and Sweden.

PURPOSE: To examine risks of adverse birth outcomes in women exposed to varenicline during pregnancy. METHODS: Population-based cohort study including live-born and stillborn infants from 1 May 2007 to 31 December 2012. Data from health and administrative registries in Denmark and Sweden, two Nordic countries with universal health care and routine registration of major life and health events. Infants were allocated to three cohorts on the basis of their in utero exposure: the exposed cohort consisting of infants whose mothers were dispensed varenicline during pregnancy; the unexposed cohort comprised infants unexposed to varenicline, but exposed to maternal smoking in utero; and the reference cohort of infants unexposed to varenicline and maternal smoking in utero. The primary outcome was major congenital malformations diagnosed from birth to the first year of life. Secondary outcomes included stillbirth, fetal growth restriction (measured as small for gestational age), preterm delivery, preterm premature rupture of membranes, and sudden infant death syndrome. We estimated the prevalence of the primary outcome and secondary outcomes in the exposed, unexposed, and reference cohorts. Prevalence odds ratios with 95% confidence intervals (CIs) were computed using logistic regression with propensity score adjustment to control for potential confounders. RESULTS: The combined cohort included 885 185 infants. Of these, 335 infants were exposed, 78 412 were unexposed, and the remaining 806 438 comprised the reference cohort. Major congenital malformations were detected among 3.6% of exposed infants, 4.3% of unexposed infants, and 4.2% of infants in the reference cohort. The propensity score-adjusted prevalence odds ratio for major congenital malformations was 0.80 (95% CI, 0.45-1.42) for exposed vs unexposed infants. All analyses of primary and secondary outcomes comparing exposed with unexposed infants yielded odds ratio estimates below or close to unity. Use of varenicline during pregnancy does not appear to increase the risk of major congenital malformations or other adverse birth outcomes.