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.

Nosocomial SARS-CoV-2 Infections and Mortality During Unique COVID-19 Epidemic Waves.

Importance: Quantifying the burden of nosocomial SARS-CoV-2 infections and associated mortality is necessary to assess the need for infection prevention and control measures. Objective: To investigate the occurrence of nosocomial SARS-CoV-2 infections and associated 30-day mortality among patients admitted to hospitals in Region Stockholm, Sweden. Design, Setting, and Participants: A retrospective, matched cohort study divided the period from March 1, 2020, until September 15, 2022, into a prevaccination period, early vaccination and pre-Omicron (period 1), and late vaccination and Omicron (period 2). From among 303 898 patients 18 years or older living in Region Stockholm, 538 951 hospital admissions across all hospitals were included. Hospitalized admissions with nosocomial SARS-CoV-2 infections were matched to as many as 5 hospitalized admissions without nosocomial SARS-CoV-2 by age, sex, length of stay, admission time, and hospital unit. Exposure: Nosocomial SARS-CoV-2 infection defined as the first positive polymerase chain reaction test result at least 8 days after hospital admission or within 2 days after discharge. Main Outcomes and Measures: Primary outcome of 30-day mortality was analyzed using time-to-event analyses with a Cox proportional hazards regression model adjusted for age, sex, educational level, and comorbidities. Results: Among 2193 patients with SARS-CoV-2 infections or reinfections (1107 women [50.5%]; median age, 80 [IQR, 71-87] years), 2203 nosocomial SARS-CoV-2 infections were identified. The incidence rate of nosocomial SARS-CoV-2 infections was 1.57 (95% CI, 1.51-1.64) per 1000 patient-days. In the matched cohort, 1487 hospital admissions with nosocomial SARS-CoV-2 infections were matched to 5044 hospital admissions without nosocomial SARS-CoV-2 infections. Thirty-day mortality was higher in the prevaccination period (adjusted hazard ratio [AHR], 2.97 [95% CI, 2.50-3.53]) compared with period 1 (AHR, 2.08 [95% CI, 1.50-2.88]) or period 2 (AHR, 1.22 [95% CI, 0.92-1.60]). Among patients with nosocomial SARS-CoV-2 infections, 30-day AHR comparing those with 2 or more doses of SARS-CoV-2 vaccination and those with less than 2 doses was 0.64 (95% CI, 0.46-0.88). Conclusions and Relevance: In this matched cohort study, nosocomial SARS-CoV-2 infections were associated with higher 30-day mortality during the early phases of the pandemic and lower mortality during the Omicron variant wave and after the introduction of vaccinations. Mitigation of excess mortality risk from nosocomial transmission should be a strong focus when population immunity is low through implementation of adequate infection prevention and control measures.

Clinical outcomes during and beyond different COVID-19 critical illness variant periods compared with other lower respiratory tract infections.

BACKGROUND: It is yet to be better understood how outcomes during and after the critical illness potentially differ between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from other lower respiratory tract infections (LRTIs). We aimed to compare outcomes in adults admitted to an intensive care unit (ICU) with coronavirus disease 2019 (COVID-19) during the Wild-type, Alpha, Delta, and Omicron periods with individuals admitted with other LRTI. METHODS: Population-based cohort study in Stockholm, Sweden, using health registries with high coverage, including ICU-admitted adults from 1 January 2016 to 15 September 2022. Outcomes were in-hospital mortality, 180-day post-discharge mortality, 180-day hospital readmission, 180-day days alive and at home (DAAH), and incident diagnoses registered during follow-up. RESULTS: The number of ICU admitted individuals were 1421 Wild-type, 551 Alpha, 190 Delta, 223 Omicron, and 2380 LRTI. In-hospital mortality ranged from 28% (n = 665) in the LRTI cohort to 35% (n = 77) in the Delta cohort. The adjusted cause-specific hazard ratio (CSHR) compared with the LRTI cohort was 1.33 (95% confidence interval [CI] 1.16-1.53) in the Wild-type cohort, 1.53 (1.28-1.82) in the Alpha cohort, 1.70 (1.30-2.24) in the Delta cohort, and 1.59 (1.24-2.02) in the Omicron cohort. Among patients discharged alive from their COVID-19 hospitalization, the post-discharge mortality rates were lower (1-3%) compared with the LRTI cohort (9%), and the risk of hospital readmission was lower (CSHRs ranging from 0.42 to 0.68). Moreover, all COVID-19 cohorts had compared with the LRTI cohort more DAAH after compared with before the critical illness. CONCLUSION: Overall, COVID-19 critical was associated with an increased hazard of in-hospital mortality, but among those discharged alive from the hospital, less severe long-term outcomes were observed compared with other LRTIs.

Post COVID-19 condition diagnosis: A population-based cohort study of occurrence, associated factors, and healthcare use by severity of acute infection.

BACKGROUND: The occurrence and healthcare use trajectory of post COVID-19 condition (PCC) is poorly understood. Our aim was to investigate these aspects in SARS-CoV-2-positive individuals with and without a PCC diagnosis. METHODS: We conducted a population-based cohort study of adults in Stockholm, Sweden, with a verified infection from 1 March 2020 to 31 July 2021, stratified by the severity of the acute infection. The outcome was a PCC diagnosis registered any time 90-360 days after a positive test. We performed Cox regression models to assess baseline characteristics associated with the PCC diagnosis. Individuals diagnosed with PCC were then propensity-score matched to individuals without a diagnosis to assess healthcare use beyond the acute infection. RESULTS: Among 204,805 SARS-CoV-2-positive individuals, the proportion receiving a PCC diagnosis was 1% among individuals not hospitalized for their COVID-19 infection, 6% among hospitalized, and 32% among intensive care unit (ICU)-treated individuals. The most common new-onset symptom diagnosis codes among individuals with a PCC diagnosis were fatigue (29%) among nonhospitalized and dyspnea among both hospitalized (25%) and ICU-treated (41%) individuals. Female sex was associated with a PCC diagnosis among nonhospitalized and hospitalized individuals, with interactions between age and sex. Previous mental health disorders and asthma were associated with a PCC diagnosis among nonhospitalized and hospitalized individuals. Among individuals with a PCC diagnosis, the monthly proportion with outpatient care was substantially elevated up to 1 year after acute infection compared to before, with substantial proportions of this care attributed to PCC-related care. CONCLUSION: The differential association of age, sex, comorbidities, and healthcare use with the severity of the acute infection indicates different trajectories and phenotypes of PCC, with incomplete resolution 1 year after infection.

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.

The early impact of vaccination against SARS-CoV-2 in Region Stockholm, Sweden.

Vaccination against SARS-CoV-2 started in Region Stockholm, Sweden in December 2020 with those in long-term care facilities or receiving home care vaccinated first followed by those aged over 80 years. In this population-based, retrospective cohort study, we performed a Poisson regression to model the expected incidence of infections and deaths which we compared to the observed incidence and compared this to an unvaccinated control group of those aged 18-79 years. The aim of this study was to measure the early impact of the vaccination programme in Region Stockholm. Infections and deaths reduced substantially amongst the first two groups targeted for SARS-CoV-2 vaccination with an estimated total 3112 infections prevented, and 854 deaths prevented in these two groups from 4 weeks after the introduction of vaccination through to 2nd May 2021.

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.

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.

Chronic Disease and Immunosuppression Increase the Risk for Nonvaccine Serotype Pneumococcal Disease: A Nationwide Population-based Study.

BACKGROUND: Demography is changing, with people living longer with comorbidities. In this nationwide population-based study, we investigated the serotype-specific invasive pneumococcal disease (IPD) risk in individuals with comorbidities, and effects of the pneumococcal conjugated vaccine (PCV) child immunization program. METHODS: Cases included 14 096 IPD episodes in Sweden during 2006-2015. Controls (n = 137 289), matched to cases by age, sex, region, and calendar time, were selected from the general population. Comorbidity data was obtained through health registers and grouped as immunocompromising (IC) or chronic medical conditions (CMC). RESULTS: The prevalence of CMC and IC among elderly cases was 33.9% and 39.4%. New risks identified for IPD were sarcoidosis, inflammatory polyarthropathies, systemic connective tissue, and neurological diseases. The odds ratio (OR) for IPD caused by non-PCV13 compared with PCV13 serotypes was higher in individuals with CMC/IC. Serotypes associated with the highest risk were 16F, 15C, 35F, 19F, and 23A (OR 3-5 for CMC, >10 for IC). Most comorbidities increased post-vaccination, and absolute increases of IPD caused by non-PCV13, PPV23-non-PCV13, and non-PCV13/non-PPV23 serotypes were higher in individuals with IC/CMC compared with healthy persons. Non-PCV13 serotypes 6C, 9N, 11A, 22F, 23A and 35F increased more in those with comorbidities. Mortality due to non-PCV13 serotypes increased in individuals with IC/CMC, while remaining stable in persons without comorbidities. CONCLUSIONS: The PCV child immunization program associates with an increased disease burden of non-vaccine serotypes in individuals with comorbidities. These data are important for vaccine design and optimization of current vaccination strategies.

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.

Pregnancy outcomes in relation to disease activity and anti-rheumatic treatment strategies in women with rheumatoid arthritis: a matched cohort study from Sweden and Denmark.

OBJECTIVES: To explore the association of maternal RA to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. METHODS: By linking prospective clinical rheumatology registers (CRR) in Sweden (the Swedish Rheumatology Quality Register, SRQ) and Denmark (the Danish clinical quality register, DANBIO) with medical birth registers, we identified 1739 RA-pregnancies and 17 390 control-pregnancies (matched 1:10 on maternal age, birth year, parity) with delivery 2006-18. Disease activity (DAS28, CRP, HAQ score) and anti-rheumatic treatment 9 months before and during pregnancy were identified through CRR and prescribed drug registers. Using logistic regression, we estimated adjusted odds ratios (aOR) with 95% CI for PTB and SGA overall and stratified by disease activity and anti-rheumatic treatment before and during pregnancy, adjusting for maternal characteristics. RESULTS: We found increased aOR of PTB [1.92 (1.56-2.35)] and SGA [1.93 (1.45-2.57)] in RA-pregnancies vs control-pregnancies. For RA-pregnancies with DAS28-CRP ≥4.1 vs <3.2 during pregnancy, aOR was 3.38 (1.52-7.55) for PTB and 3.90 (1.46-10.4) for SGA. Use of oral CS (yes/no) during pregnancy resulted in an aOR of 2.11 (0.94-4.74) for PTB. The corresponding figure for biologics was 1.38 (0.66-2.89). Combination therapy, including biologics before pregnancy, was a marker of increased risk of both PTB and SGA. CONCLUSION: During pregnancy, disease activity rather than treatment seems to be the most important risk factor for PTB and SGA in RA. Women with RA should be carefully monitored during pregnancy, especially if they have moderate to high disease activity or/and are treated with extensive anti-rheumatic treatment.

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.

Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study.

BACKGROUND: This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms. METHODS: Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA). RESULTS: The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA. CONCLUSIONS: We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.

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.

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.

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.

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.