Humoral Immune Response to SARS-CoV-2 in Iceland.

BACKGROUND: Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. RESULTS: Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. CONCLUSIONS: Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

Immediate and long-term need for permanent cardiac pacing following aortic valve replacement.

Introduction: Atrioventricular (AV) node conduction disturbances are common following surgical aortic valve replacement (SAVR), and in some cases the patient needs a permanent pacemaker (PPM) implantation before discharge from hospital. Little is known about the long-term need for PPM and the PPM dependency of these individuals. We determined the incidence of PPM implantation before and after discharge in SAVR patients. Methods: We studied 557 consecutive patients who underwent SAVR for aortic stenosis in Iceland between 2002 and 2016. Timing and indication for PPM were registered, with a new concept, ventricular pacing proportion (VPP), defined as ventricular pacing ≥90% of the time, being used to approximate pacemaker dependency. The median follow-up time was 73 months. We plotted the cumulative incidence of pacemaker implantation, treating death as a competing risk. Results: Of the 557 patients, 22 (3.9%) received PPM in the first 30 days after surgery, most commonly for complete AV block (n = 14) or symptomatic bradycardia (n = 8); Thirty-eight other patients (6.8%) had a PPM implanted >30 days postoperatively, at a median of 43 months after surgery (range 0‒181), most often for AV block (n = 13) or sick-sinus syndrome (n = 10). The cumulative incidence of PPM implantation at 1, 5, and 10 years postoperatively was 5.0%, 9.2%, and 12.3%, respectively. During follow-up, 45.0% of the 60 patients had VPP ≥90%. Conclusion: The cumulative incidence of permanent pacemaker implantation following SAVR was about 12% at 10 years, with every other patient having VPP ≥90% during follow-up. This suggests that AV node conduction disturbances extend significantly beyond the perioperative period.

Postoperative Acute Kidney Injury: Focus on Renal Recovery Definitions, Kidney Disease Progression and Survival.

BACKGROUND: The aim of this study was to examine different definitions of renal recovery following postoperative acute kidney injury (AKI) and how these definitions associate with survival and the development and progression of chronic kidney disease (CKD). METHODS: This was a retrospective study of all patients who underwent abdominal, cardiothoracic, vascular, or orthopedic surgery at a single university hospital between 1998 and 2015. Recovery of renal function following postoperative AKI was assessed comparing 4 different definitions: serum creatinine (SCr) (i) < 1.1 × baseline, (ii) 1.1-1.25 × baseline, (iii) 1.25-1.5 × baseline, and (iv) > 1.5 × baseline. One-year survival and the development or progression of CKD within 5 years was compared with a propensity score-matched control groups. RESULTS: In total, 2,520 AKI patients were evaluated for renal recovery. Risk of incident and progressive CKD within 5 years was significantly increased if patients did not achieve a reduction in SCr to < 1.5 × baseline (hazard ratio [HR] 1.50; 95% CI 1.29-1.75) and if renal recovery was limited to a fall in SCr to 1.25-1.5 × baseline (HR 1.32; 95% CI 1.12-1.57) within 30 days. The definition of renal recovery that best predicted survival was a reduction in SCr to < 1.5 × baseline within 30 days. One-year survival of patients whose SCr decreased to < 1.5 × baseline within 30 days was significantly better than that of a propensity score-matched control group that did not achieve renal recovery (85 vs. 71%, p < 0.001). CONCLUSIONS: These findings should be considered when a consensus definition of renal recovery after AKI is established.

Improved long-term outcome of surgical AVR for AS: Results from a population-based cohort.

BACKGROUND: The aim of this retrospective study was to determine changes in outcomes after surgical aortic valve replacement (SAVR) for aortic stenosis (AS) in Iceland over a 15-year period. METHODS: We included 587 patients who underwent SAVR for AS in Iceland during the period 2002-2016, with a total follow-up of 3245 patient-years. Short-term and long-term outcomes, 30-day mortality, and long-term survival (Kaplan-Meier) were analyzed. Univariate linear regression and univariate and multinomial logistic regression analyses were performed on preoperative and perioperative variables. Poisson regression analysis was used to evaluate changes in rates of short-term outcomes. RESULTS: Mean age was 71 years, 65.1% were males, and mean EuroSCORE II was 3.9. Mean preoperative aortic valve area increased significantly (0.013 cm2 /year; P < .001) and mean aortic cross-clamp time declined (108 minutes, 2.8 min/year; P < .001). The rate of complications decreased, including new-onset atrial fibrillation (60.9% overall, decreased by 3.1%/year, P = .02), acute kidney injury (17.1%, 7.6%/year, P < .001), and reoperation for bleeding (12.5%, 6.3%/year, P = .02). Operative mortality did not change (5.4%); nor did 1- and 5-year overall survival (92.5% and 81.6%, respectively). Notable long-term events were chronic heart failure (27.7 admissions/100 patient-years), embolic event (15.9/100 patient-years), and bleeding (13.0/100 patient-years). CONCLUSIONS: Results of SAVR in this well-defined nationwide cohort of patients in Iceland have improved. This may be related to the patients having less severe AS at the time of operation and shorter operating times, as reflected by lower rates of short-term complications. However, the rate of long-term complications did not change significantly, with prosthetic valve-specific events being rare.

[No significant association between obesity and long-term outcome of coronary artery bypass grafting].

OBJECTIVES:  Our objective was to investigate long-term outcomes of obese patients undergoing coronary artery bypass grafting (CABG) in Iceland. MATERIALS AND METHODS:  A retrospective analysis on 1698 patients that underwent isolated CABG in Iceland between 2001-2013. Patients were divided into four groups according to body mass index (BMI); Normal=18.5-24.9kg/m2 (n=393), ii) overweight=25-29.9 kg/m2 (n=811), iii) obese=30-34.9 kg/m2 (n=388) and iv) severely obese ≥35kg/m2 (n=113). Thirty-day mortality and short-term complications were documented as well as long-term complications that were pooled into major adverse cardiac and cerebrovascular events (MACCE) and included myocardial infarction, stroke, repeated CABG, percutaneous coronary intervention with or without stenting, and death. After pooling the study groups, survival and freedom from MACCE plots (Kaplan- Meier) were generated and Cox regression analysis used to identify predictive factors of survival. Average follow-up time was 5.6 years. RESULTS:  Severely obese and obese patients were significantly younger than those with a normal BMI, more often males with identifiable risk factors of coronary artery disease (CAD) and a lower EuroSCORE II (1.6 vs. 2.7, p=0.002). The incidence of major early complications, 30-day mortality (2%), long-term survival (90% at 5 years, log-rank test p=0.088) and MACCE-free survival (81% at 5 years, log-rank test p=0.7) was similar for obese and non-obese patients. BMI was neither an independent predictor for long-term (OR: 0.98 95%-CI: 0.95-1.01) nor MACCE-free survival (OR: 1.0 95%-CI: 0.98-1.02).  Conclusions: Obese patients that undergo CABG in Iceland are younger and have an increased number of risk factors for coronary disease when compared to non-obese patients. However, BMI neither predicted long-term survival or long-term complications. The outcomes following CABG in obese patients are good in Iceland.

[Early outcome of surgical aortic valve replacement for aortic stenosis in Icelandic females].

INTRODUCTION: Aortic valve replacement (AVR) for aortic stenosis (AS) is the second most common open-heart procedure performed in Iceland. The aim of this study was to analyze the early outcome of AVR among females in Iceland. MATERIALS AND METHODS: This was a retrospective study including 428 patients who underwent surgical AVR due to AS in Iceland from 2002-2013. Information was gathered from medical records, including pre- and postoperative results of echocardiography and complications. Overall survival was estimated (Kaplan-Meier) and logistic regression used to identify predictors of operative mortality. The median follow-up time was 8.8 years (0-16.5 years). RESULTS: Of the 428 patients, 151 were female (35.3%), that were on average 2 years older than men (72.6 ± 9.4 vs. 70.4 ± 9.8 yrs., p=0.020). Preoperative symptoms were similar, but women had significantly higher EurosSCORE II than men (5.2 ± 8.8 vs. 3.2 ± 4.6, p=0.002). Maximal pressure-gradient across the aortic valve was higher for women (74.4 ± 29.3 mmHg vs. 68.0 ± 23.4 mmHg, p=0,013) but postoperative complications, operative mortality (8.6% vs. 4.0%, p=0.068) and 5-year survival (78.6% vs. 83.1%, p=0.245) were comparable for women and men. Logistic regression analysis showed that female gender was not an independent predictor of 30-day mortality (OR 1.54, 95% CI 0.63-3.77). CONCLUSIONS: Females constitute one third of patients that undergo AVR for AS in Iceland. At the time of surgery females are two years older than men and appear to have a more significant aortic stenosis at the time of surgery. However, complication rates, operative mortality and long-term survival were comparable for both genders.

Favourable long-term outcome after coronary artery bypass grafting in a nationwide cohort.

OBJECTIVES: In a nationwide cohort, we analyzed long-term outcome following coronary artery bypass grafting, using the combined strategy of left internal mammary artery to the left anterior descending artery and saphenous vein as secondary graft to other coronary targets. METHODS: 1,507 consecutive patients that underwent myocardial revascularization during 2001-2012 in Iceland. Mean follow-up was 6.8 years. Major adverse cardiac and cerebrovascular events were depicted using the Kaplan-Meier method. Cox-regression was used to define risk factors. Relative survival was estimated by comparing overall survival to the survival of Icelanders of the same age and gender. RESULTS: Mean age was 66 years, 83% were males, mean EuroSCOREst was 4.5, and 23% of the procedures were performed off-pump. At 5 years, 19.7% had suffered a major adverse cardiac or cerebrovascular event, 4.5% a stroke, 2.2% myocardial infarction, and 6.2% needed repeat revascularization. Overall 5-year survival was 89.9%, with a relative survival of 0.990. Independent predictors of major adverse cardiac and cerebrovascular events were left ventricular ejection fraction ≤30%, a previous history of percutaneous coronary intervention, chronic obstructive lung disease, chronic kidney disease, diabetes, and old age. The same variables and an earlier year of operation were predictors of long-term mortality. CONCLUSIONS: The long-term outcome following myocardial revascularization, using the left internal mammary artery and the great saphenous vein as conduits, is favourable and improving. This is reflected by the 5-year survival of 89.9%, deviating minimally from the survival rate of the general Icelandic population, together with a freedom from major adverse cardiac and cerebrovascular events of 80.3%.

Favorable Survival after Aortic Valve Replacement Compared to the General Population.

BACKGROUND: A comparison was made between the long-term survival of patients undergoing aortic valve replacement (AVR) for aortic stenosis and of the general Icelandic population, using centralized registries. METHODS: A total of 366 AVR patients (231 males, 135 females; mean age 70.1 years) operated on for aortic stenosis in Iceland between 2002 and 2011 was included in the study. Concomitant coronary artery bypass grafting was performed in 54% of cases. Short-term complications and 30-day mortality were analyzed. The patients' overall survival was compared with the survival of Icelanders of the same age and gender. The median follow up was 4.7 years. RESULTS: A bioprosthesis was used in 81% of the patients; the median prosthesis size was 25 mm. Atrial fibrillation (68%) and acute kidney injury (23%) were the most common complications, and the 30-day operative mortality was 6%. Overall survival at one year and five years was 92% and 82%, respectively. There was no difference in survival between the surgical cohorts and expected survival of Icelanders of the same age and gender (p = 0.08), except for the first 30 postoperative days. CONCLUSIONS: Despite the significant rate of short-term complications, the long-term survival of patients undergoing AVR for aortic stenosis was good compared to the general population of the same age and gender. These results confirmed the value of AVR as an excellent treatment option for aortic stenosis, as it offers a normalization of the patients' life expectancy.

Acute Kidney Injury After Abdominal Surgery: Incidence, Risk Factors, and Outcome.

BACKGROUND: Acute kidney injury (AKI) is a serious complication after major surgical procedures. We examined the incidence, risk factors, and mortality of patients who sustained AKI after abdominal surgery in a large population-based cohort. METHODS: All patients who underwent open and laparoscopic abdominal surgery (excluding genitourinary and abdominal vascular procedures), between 2007 and 2014 at the University Hospital in Reykjavik were identified and their perioperative serum creatinine (SCr) measurements used to identify AKI after surgery employing the Kidney Disease: Improving Global Outcome (KDIGO) criteria. Risk factors were evaluated using multivariate logistic regression analysis and 30-day mortality compared with a propensity score-matched control group. RESULTS: During the 8-year period, a total of 11,552 abdominal surgeries were performed on 10,022 patients. Both pre- and postoperative SCr measurements were available for 3902 (33.8%) of the surgical cases. Of these, 264 (6.8%) were complicated by AKI; 172 (4.4%), 49 (1.3%), and 43 (1.1%) were classified as KDIGO stages 1, 2 and 3, respectively. The overall incidence of AKI for patients with available SCr values was 67.7 (99% confidence interval [CI], 57.7-78.6) per 1000 surgeries. In logistic regression analysis, independent risk factors for AKI were female sex (odds ratio [OR] = 0.68; 99% CI, 0.47-0.98), hypertension (OR = 1.75; 99% CI, 1.10-2.74), preoperative chronic kidney disease (OR= 1.68; 99% CI, 1.12-2.50), ASA physical status classification of IV (OR = 9.48; 99% CI, 3.66-29.2) or V (OR = 21.4; 99% CI, 5.28-93.6), and reoperation (OR = 4.30; 99% CI, 2.36-7.70). Patients with AKI had greater 30-day mortality (18.2% vs 5.3%; P < 0.001) compared with propensity score-matched controls. CONCLUSIONS: AKI is an important complication of abdominal surgery. In addition to sex, hypertension, and chronic kidney disease, ASA physical status classification is an independent predictor of AKI. Individuals who develop AKI have substantially worse short-term outcomes, including higher 30-day mortality, even after correcting for multiple patient- and procedure-related risk factors.

Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study.

BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.

Persistent symptoms are commonly reported after SARS-CoV-2 infection, and this is often described as long Covid. We compared different symptoms reported following SARS-CoV- 2 infection with the results obtained during various medical evaluations that are often used to assess health, such as blood tests, smell tests, taste tests, hearing tests, etc. We compared symptoms and test results between 1,706 Icelanders who had been infected previously with SARS-CoV-2 infection (cases) and 14,398 individuals who had not been infected (controls). Out of 88 assessed symptoms, 41 were more common in cases than controls. However, relatively few differences were seen in the results obtained from the various medical evaluations (cases had poorer smell and taste test results, slightly less grip strength, and slightly poorer memory recall than controls). The differences seen between symptoms and results of medical evaluations suggests that conventional clinical tests may not be informative in relating symptoms to a past SARS-CoV-2 infection.

Development of a prognostic model of COVID-19 severity: a population-based cohort study in Iceland.

BACKGROUND: The severity of SARS-CoV-2 infection varies from asymptomatic state to severe respiratory failure and the clinical course is difficult to predict. The aim of the study was to develop a prognostic model to predict the severity of COVID-19 in unvaccinated adults at the time of diagnosis. METHODS: All SARS-CoV-2-positive adults in Iceland were prospectively enrolled into a telehealth service at diagnosis. A multivariable proportional-odds logistic regression model was derived from information obtained during the enrollment interview of those diagnosed between February 27 and December 31, 2020 who met the inclusion criteria. Outcomes were defined on an ordinal scale: (1) no need for escalation of care during follow-up; (2) need for urgent care visit; (3) hospitalization; and (4) admission to intensive care unit (ICU) or death. Missing data were multiply imputed using chained equations and the model was internally validated using bootstrapping techniques. Decision curve analysis was performed. RESULTS: The prognostic model was derived from 4756 SARS-CoV-2-positive persons. In total, 375 (7.9%) only required urgent care visits, 188 (4.0%) were hospitalized and 50 (1.1%) were either admitted to ICU or died due to complications of COVID-19. The model included age, sex, body mass index (BMI), current smoking, underlying conditions, and symptoms and clinical severity score at enrollment. On internal validation, the optimism-corrected Nagelkerke's R2 was 23.4% (95%CI, 22.7-24.2), the C-statistic was 0.793 (95%CI, 0.789-0.797) and the calibration slope was 0.97 (95%CI, 0.96-0.98). Outcome-specific indices were for urgent care visit or worse (calibration intercept -0.04 [95%CI, -0.06 to -0.02], Emax 0.014 [95%CI, 0.008-0.020]), hospitalization or worse (calibration intercept -0.06 [95%CI, -0.12 to -0.03], Emax 0.018 [95%CI, 0.010-0.027]), and ICU admission or death (calibration intercept -0.10 [95%CI, -0.15 to -0.04] and Emax 0.027 [95%CI, 0.013-0.041]). CONCLUSION: Our prognostic model can accurately predict the later need for urgent outpatient evaluation, hospitalization, and ICU admission and death among unvaccinated SARS-CoV-2-positive adults in the general population at the time of diagnosis, using information obtained by telephone interview.

HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2.

Memory T-cell responses following SARS-CoV-2 infection have been extensively investigated but many studies have been small with a limited range of disease severity. Here we analyze SARS-CoV-2 reactive T-cell responses in 768 convalescent SARS-CoV-2-infected (cases) and 500 uninfected (controls) Icelanders. The T-cell responses are stable three to eight months after SARS-CoV-2 infection, irrespective of disease severity and even those with the mildest symptoms induce broad and persistent T-cell responses. Robust CD4+ T-cell responses are detected against all measured proteins (M, N, S and S1) while the N protein induces strongest CD8+ T-cell responses. CD4+ T-cell responses correlate with disease severity, humoral responses and age, whereas CD8+ T-cell responses correlate with age and functional antibodies. Further, CD8+ T-cell responses associate with several class I HLA alleles. Our results, provide new insight into HLA restriction of CD8+ T-cell immunity and other factors contributing to heterogeneity of T-cell responses following SARS-CoV-2 infection.

Mild Stage 1 post-operative acute kidney injury: association with chronic kidney disease and long-term survival.

BACKGROUND: Mild cases of acute kidney injury (AKI) are identified by a small rise in serum creatinine (SCr) according to the KDIGO AKI definition. The aim of this study was to examine the long-term outcomes of individuals with mild AKI.Methods. This was a retrospective cohort study of all adult patients who underwent abdominal, cardiothoracic, vascular or orthopaedic surgery at Landspitali-The National University Hospital of Iceland in 1998-2015. Incident chronic kidney disease (CKD), progression of pre-existing CKD and long-term survival were compared between patients with mild Stage 1 AKI (defined as a rise in SCr of ≥26.5 µmol/L within 48 h post-operatively without reaching 1.5× baseline SCr within 7 days), and a propensity score-matched control group without AKI stratified by the presence of CKD. RESULTS: Pre- and post-operative SCr values were available for 47 333 (42%) surgeries. Of those, 1161 (2.4%) had mild Stage 1 AKI and 2355 (5%) more severe forms of AKI. Mild Stage 1 AKI was associated with both incident CKD and progression of pre-existing CKD (P < 0.001). After exclusion of post-operative deaths within 30 days, mild Stage 1 AKI was not associated with worse 1-year survival in patients with preserved kidney function (94% versus 94%, P = 0.660), and same was true for patients with pre-operative CKD (83% versus 82%, P = 0.870) compared with their matched individuals. Conclusions. Mild Stage 1 AKI is associated with development and progression of CKD, but not with inferior 1-year survival. These findings support the inclusion of a small absolute increase in SCr in the definition of AKI.

Acute Kidney Injury After Acute Repair of Type A Aortic Dissection.

BACKGROUND: The aim of this study was to examine the incidence, risk factors, and outcomes of patients with acute kidney injury (AKI) after surgery for acute type A aortic dissection (ATAAD) using the Nordic Consortium for Acute Type A Aortic Dissection registry. METHODS: Patients who underwent ATAAD surgery at 8 Nordic centers from 2005 to 2014 were analyzed for AKI according to the RIFLE criteria. Patients who died intraoperatively, those who had missing baseline or postoperative serum creatinine, and patients on preoperative renal replacement therapy were excluded. RESULTS: AKI occurred in 382 of 941 patients (40.6%), and postoperative dialysis was required for 105 patients (11.0%). Renal malperfusion was present preoperatively in 42 patients (5.1%), of whom 69.0% developed postoperative AKI. In multivariable analysis patient-related predictors of AKI included age (per 10 years; odds ratio [OR], 1.30; 95% confidence interval [CI], 1.15-1.48), body mass index >30 kg/m2 (OR, 2.16; 95% CI, 1.51-3.09), renal malperfusion (OR, 4.39; 95% CI, 2.23-9.07), and other malperfusion (OR, 2.10; 95% CI, 1.55-2.86). Perioperative predictors were cardiopulmonary bypass time (per 10 minutes; OR, 1.04; 95% CI, 1.02-1.07) and red blood cell transfusion (OR per transfused unit, 1.08; 95% CI, 1.06-1.10). Rates of 30-day mortality were 17.0% in the AKI group compared with 6.6% in the non-AKI group (P < .001). In 30-day survivors AKI was an independent predictor of long-term mortality (hazard ratio, 1.86; 95% CI; 1.24-2.79). CONCLUSIONS: AKI is a common complication after surgery for ATAAD and independently predicts adverse long-term outcome. Of note one-third of patients presenting with renal malperfusion did not develop postoperative AKI, possibly because of restoration of renal blood flow with surgical repair. Mortality risk persists beyond the perioperative period, indicating that close clinical follow-up of these patients is required.

Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study.

Multiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS. We conducted a large population-based cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 among individuals with MGUS. We included 75,422 Icelanders born before 1976, who had been screened for MGUS in the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). Data on SARS-CoV-2 testing and COVID-19 severity were acquired from the Icelandic COVID-19 Study Group. Using a test-negative study design, we included 32,047 iStopMM participants who had been tested for SARS-CoV-2, of whom 1754 had MGUS. Among these participants, 1100 participants, tested positive, 65 of whom had MGUS. Severe COVID-19 developed in 230 participants, including 16 with MGUS. MGUS was not associated with SARS-CoV-2 infection (Odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81-1.36; p = 0.72) or severe COVID-19 (OR: 0.99; 95%CI: 0.52-1.91; p = 0.99). These findings indicate that MGUS does not affect the susceptibility to SARS-CoV-2 or the severity of COVID-19.

Long-term outcomes after coronary artery bypass surgery in patients with diabetes.

OBJECTIVES: Our aim was to investigate the outcome of patients with diabetes undergoing coronary artery bypass grafting (CABG) surgery in a whole population with main focus on long-term mortality and complications. METHODS: This was a nationwide retrospective analysis of all patients who underwent isolated primary CABG in Iceland between 2001 and 2016. Overall survival together with the composite end point of major adverse cardiac and cerebrovascular events was compared between patients with diabetes and patients without diabetes during a median follow-up of 8.5 years. Multivariable regression analyses were used to evaluate the impact of diabetes on both short- and long-term outcomes. RESULTS: Of a total of 2060 patients, 356 (17%) patients had diabetes. Patients with diabetes had a higher body mass index (29.9 vs 27.9 kg/m2) and more often had hypertension (83% vs 62%) and chronic kidney disease (estimated glomerular filtration rate ≤60 ml/min/1.73 m2, 21% vs 14%). Patients with diabetes had an increased risk of operative mortality [odds ratio 2.52, 95% confidence interval (CI) 1.27-4.80] when adjusted for confounders. 5-Year overall survival (85% vs 91%, P < 0.001) and 5-year freedom from major adverse cardiac and cerebrovascular events were also inferior for patients with diabetes (77% vs 82%, P < 0.001). Cox regression analysis adjusting for potential confounders showed that the diagnosis of diabetes significantly predicted all-cause mortality [hazard ratio (HR) 1.87, 95% CI 1.53-2.29] and increased risk of major adverse cardiac and cerebrovascular events (HR 1.47, 95% CI 1.23-1.75). CONCLUSIONS: Patients with diabetes have significantly lower survival after CABG, both within 30 days and during long-term follow-up.

Clinical spectrum of coronavirus disease 2019 in Iceland: population based cohort study.

OBJECTIVE: To characterise the symptoms of coronavirus disease 2019 (covid-19). DESIGN: Population based cohort study. SETTING: Iceland. PARTICIPANTS: All individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR) between 17 March and 30 April 2020. Cases were identified by three testing strategies: targeted testing guided by clinical suspicion, open invitation population screening based on self referral, and random population screening. All identified cases were enrolled in a telehealth monitoring service, and symptoms were systematically monitored from diagnosis to recovery. MAIN OUTCOME MEASURES: Occurrence of one or more of 19 predefined symptoms during follow-up. RESULTS: Among 1564 people positive for SARS-CoV-2, the most common presenting symptoms were myalgia (55%), headache (51%), and non-productive cough (49%). At the time of diagnosis, 83 (5.3%) individuals reported no symptoms, of whom 49 (59%) remained asymptomatic during follow-up. At diagnosis, 216 (14%) and 349 (22%) people did not meet the case definition of the Centers for Disease Control and Prevention and the World Health Organization, respectively. Most (67%) of the SARS-CoV-2-positive patients had mild symptoms throughout the course of their disease. CONCLUSION: In the setting of broad access to RT-PCR testing, most SARS-CoV-2-positive people were found to have mild symptoms. Fever and dyspnoea were less common than previously reported. A substantial proportion of SARS-CoV-2-positive people did not meet recommended case definitions at the time of diagnosis.

Association Between Preoperative Opioid and Benzodiazepine Prescription Patterns and Mortality After Noncardiac Surgery.

Importance: The number of patients prescribed long-term opioids and benzodiazepines and complications from their long-term use have increased. Information regarding the perioperative outcomes of patients prescribed these medications before surgery is limited. Objective: To determine whether patients prescribed opioids and/or benzodiazepines within 6 months preoperatively would have greater short- and long-term mortality and increased opioid consumption postoperatively. Design, Setting, and Participants: This retrospective, single-center, population-based cohort study included all patients 18 years or older, undergoing noncardiac surgical procedures at a national hospital in Iceland from December 12, 2005, to December 31, 2015, with follow-up through May 20, 2016. A propensity score-matched control cohort was generated using individuals from the group that received prescriptions for neither medication class within 6 months preoperatively. Data analysis was performed from April 10, 2018, to March 9, 2019. Exposures: Patients who filled prescriptions for opioids only, benzodiazepines only, both opioids and benzodiazepines, or neither medication within 6 months preoperatively. Main Outcomes and Measures: Long-term survival compared with propensity score-matched controls. Secondary outcomes were 30-day survival and persistent postoperative opioid consumption, defined as a prescription filled more than 3 months postoperatively. Results: Among 41 170 noncardiac surgical cases in 27 787 individuals (16 004 women [57.6%]; mean [SD] age, 56.3 [18.8] years), a preoperative prescription for opioids only was filled for 7460 cases (17.7%), benzodiazepines only for 3121 (7.4%), and both for 2633 (6.2%). Patients who filled preoperative prescriptions for either medication class had a greater comorbidity burden compared with patients receiving neither medication class (Elixhauser comorbidity index >0 for 16% of patients filling prescriptions for opioids only, 22% for benzodiazepines only, and 21% for both medications compared with 14% for patients filling neither). There was no difference in 30-day (opioids only: 1.3% vs 1.0%; P = .23; benzodiazepines only: 1.9% vs 1.5%; P = .32) or long-term (opioids only: hazard ratio [HR], 1.12 [95% CI, 1.01-1.24]; P = .03; benzodiazepines only: HR, 1.11 [95% CI, 0.98-1.26]; P = .11) survival among the patients receiving opioids or benzodiazepines only compared with controls. However, patients prescribed both opioids and benzodiazepines had greater 30-day mortality (3.2% vs 1.8%; P = .004) and a greater hazard of long-term mortality (HR, 1.41; 95% CI, 1.22-1.64; P < .001). The rate of persistent postoperative opioid consumption was higher for patients filling prescriptions for opioids only (43%), benzodiazepines only (23%), or both (66%) compared with patients filling neither (12%) (P < .001 for all). Conclusions and Relevance: The findings suggest that opioid and benzodiazepine prescription fills in the 6 months before surgery are associated with increased short-and long-term mortality and an increased rate of persistent postoperative opioid consumption. These patients should be considered for early referral to preoperative clinic and medication optimization to improve surgical outcomes.

Acute kidney injury following coronary angiography: a nationwide study of incidence, risk factors and long-term outcomes.

BACKGROUND: We studied the incidence and risk factors of acute kidney injury (AKI) following coronary angiography (CA) and examined short- and long-term outcomes of patients who developed AKI, including progression of chronic kidney disease (CKD). METHODS: This was a retrospective study of all patients undergoing CA in Iceland from 2008 to 2015, with or without percutaneous coronary intervention. All procedures were performed with iso-osmolar contrast. AKI was defined according to the SCr component of the KDIGO criteria. Patients without post-procedural SCr were assumed to be free of AKI. Incident CKD was defined as 90-day sustained estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and progression of CKD as worsening at least one stage sustained over 90 days. RESULTS: AKI was detected in 231 of 13,561 cases (1.7%). There was an interaction between contrast dose and preexisting kidney function, where the risk for AKI was only significant at a dose > 150 mL in patients with baseline eGFR < 45 mL/min/1.73 m2 (OR 5.3, 95% CI 2.1-14.2). The AKI patients had worse short-and long-term survival, as well as elevated hazard of both new-onset CKD (HR 3.7, 95% CI 2.7-5.0) and progression of preexisting CKD (HR 2.0, 95% CI 1.5-2.6) over a median follow-up of 3.3 years (range 0.1-8.4 years), compared to a propensity score-matched control group. CONCLUSIONS: For iso-osmolar contrast, the risk of AKI related to contrast dose was evident for higher amount of contrast in patients with baseline eGFR < 45 mL/min/1.73 m2. In addition to association with adverse short- and long-term survival AKI had a strong association with new-onset or progression of CKD when patients were followed longitudinally.