Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Complications, quality of life and outcome after free flap surgery for cancer of the head and neck

Abstract Free flap surgery (FFS) is used for the reconstruction of head and neck defects after tumor resection. Compared to many other cancers requiring operative care, postoperative complications are frequent and the long-term outcome is poor in this patient group. The impact of postoperative complications on outcome, quality of life (QOL) and causes of death has not been well studied. The aim of this thesis was to study the factors associated with postoperative complications after FFS for cancer of the head and neck, as well as the impact of complications on QOL and long-term outcomes. The thesis includes one prospective and three retrospective studies. The study population was 146 head and neck patients undergoing FFS in Oulu University Hospital from 2008 to 2016. The impact of goal-directed fluid management using SVV (stroke volume variation) analysis on postoperative outcome was evaluated retrospectively. It led to a significant reduction in intraoperative fluid administration (6070 ml vs. 8185 ml) and length of stay (LOS) in hospital (11.5 vs. 14.0 days) but had no impact on the rate of postoperative complications. Postoperative complications were recorded in 60% of the patients and were related to alcohol abuse, complicated intraoperative course and fibular flap surgery. The patients with late complications (occurring after the fourth postoperative day) had higher mortality compared to those without. The QOL of 53 patients undergoing operations during 2013–2016 was evaluated using four questionnaires. Patients with medical complications (n=12, 22.6%) had significantly lower QOL in most domains of RAND-36 but QOL for those without complications was comparable to the general population. A total of 62/146 patients (42.5%) died by the end of 2016, and in 72.6% of cases the cause of death was the primary disease. In multivariate analysis male gender, low BMI, ASA above 2 and late medical complications were indicative for long-term mortality. In conclusion, postoperative complications have an impact on outcome after FFS for cancer of the head and neck in terms of QOL and long-term mortality. Patient-related factors were associated with unfavorable outcomes when intraoperative factors did not have as significant a role. Prevention of medical complications and adequate patient selection are essential when aiming to improve outcome after FFS.Tiivistelmä Mikrovaskulaarikielekkeitä käytetään korjaamaan kasvaimen poiston vuoksi syntyneitä kudospuutoksia pään ja kaulan alueen syöpäpotilailla. Näihin toimenpiteisiin liittyy merkittävä komplikaatioriski ja myös itse syövän pitkäaikaisennuste on huono. Komplikaatioiden vaikutusta toipumisvaiheen elämänlaatuun ja kuolleisuuteen ei ole tutkittu. Tämän väitöskirjatyön tavoitteena oli selvittää tekijöitä, jotka liittyvät leikkauksen jälkeisiin komplikaatioihin, ja niiden merkitystä potilaiden elämänlaatuun ja pitkäaikaisennusteeseen. Tutkimuskokonaisuus koostuu kolmesta retrospektiivisestä tutkimuksesta ja yhdestä prospektiivisesta haastattelututkimuksesta. Tutkimukseen kuului 146 vuosina 2008–2016 Oulun yliopistollisessa sairaalassa leikattua pään ja kaulan alueen syöpäpotilasta. Tutkimuksessa selvitettiin tavoiteohjatun nestehoidon vaikutusta välittömään toipumisvaiheeseen, mutta tällä ei todettu olevan vaikutusta komplikaatioiden ilmaantumiseen. Sen sijaan potilaiden saama nestemäärä väheni merkitsevästi (6070 ml vs. 8185 ml) ja sairaalahoitojakson pituus lyheni (11,5 päivää vs. 14 päivää). Komplikaatioita todettiin 60 % leikkauksista ja useimmin komplikaation sai potilas, jolla oli alkoholin liikakäyttöä, ongelmia toimenpiteen aikana ja luullinen siirre. Neljännen leikkauksen jälkeisen päivän jälkeen ilmenneisiin komplikaatioihin liittyi korkeampi pitkäaikaiskuolleisuus. Elämänlaatu arvioitiin 53 potilaalta, jotka oli leikattu vuosina 2013–2016. Ei-kirurgisia komplikaatioita esiintyi 12 potilaalla ja heidän raportoimansa elämänlaatu oli merkitsevästi alentunut verrattuna muihin potilaisiin. Ilman komplikaatioita toipuneiden elämänlaatu oli verrattavissa väestöarvoihin. 42,5 % leikatuista potilaista oli kuollut vuoden 2016 loppuun mennessä ja 72,6 % heistä kuolema johtui hoidetusta syövästä. Monimuuttujamallissa pitkäaikaiskuolleisuuden riskitekijöitä olivat miessukupuoli, matala BMI, ASA-luokka yli 2 sekä todetut ei-kirurgiset komplikaatiot. Yhteenvetona voidaan todeta, että komplikaatioilla on merkitystä toipumisvaiheen elämänlaatuun ja pitkäaikaiskuolleisuuteen tässä potilasryhmässä. Potilaslähtöiset tekijät vaikuttavat merkittävästi komplikaatioiden ilmaantumiseen ja myös huonoon ennusteeseen. Ei-kirurgisten komplikaatioiden estäminen kuten myös oikea potilasvalinta ovat keskeisessä asemassa, kun tämän potilasryhmän hoidon tuloksia halutaan parantaa

Quality of life after free flap reconstruction for the cancer of the head and neck:comparison between five-year survivors and non-survivors

Abstract Background: Free flap surgery due to the cancer of the head and neck includes high risk of postoperative complications and a five-year mortality up to 50%. We aimed to study the relation between the quality of life (QoL) reported two years after the operation and the mortality during a next three-year follow-up. We aimed to study the relation between the quality of life (QoL) reported two years after the operation and the mortality during a next three-year follow-up. Methods: Free flap surgery due to the cancer of the head and neck includes high risk of postoperative complications and a five-year mortality up to 50%. We aimed to study the relation between the quality of life (QoL) reported two years after the operation and the mortality during a next three-year follow-up. We aimed to study the relation between the quality of life (QoL) reported two years after the operation and the mortality during a next three-year follow-up. Results: A total of 14 (26.4%) patients died during the follow-up. The RAND-36 scores of the deceased were lower in domains “general health”, “energy”, “emotional role functioning” and “emotional well-being”. In UW-QOL tool, the domains “swallowing“ and “mood”, as well as experienced QoL were lower in the non-survivors. In EORTC QLQ assessment the non-survivors reported lower QoL in domains “global health status“, “physical functioning”, “role functioning“, “swallowing”, and “felt ill“. Conclusions: Based on our results, poor long-term survival is related to poor QoL reported two years after surgery. The difference was found in general domains of QoL tools indicating that poor QoL is a surrogate of chronic health problems having an impact on the long-term survival

Causes of nutrition deficit during immediate postoperative period after free flap surgery for cancer of the head and neck

Abstract Purpose: The aim of the present of study was to examine nutrition deficit during the immediate postoperative in-hospital period following free flap surgery for cancer of the head and neck (HNC). Underfeeding and malnutrition are known to be associated with impaired short- and long-time recovery after major surgery. Methods: This single-center retrospective cohort study included 218 HNC patients who underwent free flap surgery in Oulu University Hospital, Finland between the years 2008 and 2018. Nutrition delivery methods, the adequacy of nutrition and complication rates were evaluated during the first 10 postoperative days. Results: A total of 131 (60.1%) patients reached nutritional adequacy of 60% of calculated individual demand during the follow-up period. According to multivariate analysis, nutrition inadequacy was associated with higher ideal body weight (OR 1.11 [1.04–1.20]), whereas adequate nutrition was associated with higher number of days with oral food intake (OR 0.79 [0.67–0.93]). Conclusion: Inadequate nutrition is common after HNC free flap surgery. The present results suggest that more adequate nutrition delivery might be obtained by the early initiation of oral food intake and close monitoring of nutrition support

Accuracy of dispatch and prehospital triage performance in poisonings:a retrospective study from northern Finland

Abstract Background: Increasing numbers of dispatches place a burden on EMS; this study sought to assess the prehospital evaluation of poisoned patients transported to hospital. The primary aim of this study was to measure dispatch centre and EMS provider performance as well as factors contributing to the recognition of poisoning among prehospital patients. The secondary aim was to compare triage performance between dispatch centres and EMS providers. Methods: A retrospective single-centre study in Northern Finland was conducted. Patients suspected as poisonings by dispatch centres as well as other EMS-transported patients who received a diagnosis of poisoning in hospital between June 1, 2015 and June 1, 2017, were included. Results: There were a total of 1668 poisoning-related EMS missions. Dispatch centres suspected poisonings with sensitivity of 79.9% (95% CI 76.7–82.9) and specificity of 98.9% (95% CI 98.9–99.0) when all EMS missions were taken into account. In a logistic regression model, decreased state of consciousness as dispatch code (OR 7.18, 95% CI 1.90–27.05) and intravenous fluid resuscitation (OR 6.58, 95% CI 1.34–32.37) were associated with EMS transport providers not recognizing poisoning. Overtriage rate appeared significantly higher (33.6%, 95% CI 28.6–39.2) for dispatch when compared with transport (17.8%, 95% CI 13.9–22.6). Conclusion: Dispatch centres seem to suspect poisonings fairly accurately. Poisonings unrecognized by EMS providers may be linked with intravenous fluid resuscitation and decreased patient consciousness. Overtriage appears to resolve somewhat from dispatch to transport. There were no fatal poisonings in this study population

Early impact of the COVID-19 pandemic and social restrictions on ambulance mission

Abstract Background:The SARS-CoV-2 coronavirus disease 2019 (COVID-19) has had a major impact on health care services globally. Recent studies report that emergency departments have experienced a significant decline in the number of admitted patients in the early phase of the pandemic. To date, research regarding the influence of COVID-19 on emergency medical services (EMS) is limited. This study investigates a change in the number and characteristics of EMS missions in the early phase of the pandemic. Methods:All EMS missions in the Northern Ostrobothnia region, Finland (population 295 500) between 1 March to 30 June 2020 were screened and analyzed as the study group. A control group was composed from the EMS calls between the corresponding months in the years 2016–19. Results:A total of 74 576 EMS missions were screened for the study. Within the first 2 months after the first COVID-19 cases in the study area, the decline in the number of EMS missions was 5.7–13% compared with the control group average. EMS time intervals (emergency call to dispatch, dispatch, en-route, on-scene and hospital handover) prolonged in the COVID-19 period. Dispatches concerning mental health problems increased most in the study period (+1.2%, P < 0.001). Only eleven confirmed COVID-19 infections were encountered by EMS in the study period. Conclusions: Our findings suggest that the present COVID-19 pandemic and social restrictions lead to changes in the EMS usage. These preliminary findings emphasize the importance of developing new strategies and protocols in response to the oncoming pandemic waves

Perioperative risk factors for one-year mortality in patients with free-flap reconstruction due to cancer of the head and neck

Abstract Purpose: Head and neck cancer requiring free-flap reconstruction is associated with relatively high mortality. We aimed to evaluate perioperative risk factors for 1-year mortality in this patient group. Methods: This is a single-center retrospective analysis of 204 patients operated during 2008 to 2018. Results: A total of 47 (23.0%) patients died within 1 year. In univariate analysis, there were no differences in the intraoperative course between 1-year survivors and nonsurvivors. Among the 1-year nonsurvivors, preoperative albumin level was lower (39 [36 to 43] vs 42 [39 to 44], P = 0.032) and the Sequential Organ Failure Assessment admission score was higher (4 [3 to 5] vs 3 [2 to 4], P = 0.003) than those of the 1-year survivors. Among the nonsurvivors, the preoperative and postoperative levels of leukocytes were higher (7.6 [6.7 to 9.5] vs 6.9 [5.5 to 8.4], P = 0.002; 11.4 [9.0 to 14.2] vs 8.7 [7.2 to 11.3], P < 0.001). The highest odds ratios for 1-year mortality in multivariate analysis were American Society of Anesthesiologists A classification greater than 2 (3.9 CI 1.4 to 10.5), male gender (4.0 CI 1.5 to 11), and increase in leukocyte count (1.3 CI 1.1 to 1.5). Conclusions: One-year nonsurvivors had higher American Society of Anesthesiologists classification and were more often men. The postoperative inflammatory markers were higher in nonsurvivors, while the intraoperative course did not have a significant impact on the 1-year mortality

Quality of life in head and neck cancer patients at 5 years after free flap reconstruction:a significant decline during the follow-up

Abstract Purpose: Free flap reconstructions following head and neck tumor resection are known to involve more than 50% rate of complications and other adverse events and up to 50% mortality during a 5-year follow-up. We aimed to examine the difference in the long-term quality of life (QoL) between the 2-year and 5-year assessments after free flap surgery for cancer of the head and neck. Methods: A total of 28 of the 39 eligible patients responded to the survey. QoL was assessed at 5 years after operation and compared with the assessment performed at 2 years after the operation using RAND-36, EORTC-C30 and H&N-35, and SWAL-QOL tools. Results: The criteria for poor QoL using RAND-36 tool was met in 11 (39.3%) patients in contrast to 4 (14.3%, P = 0.003) patients in the 2-year assessment. EORTC-C30 global score was decreased from 83.9 (SD16.4) to 64.6 (SD 24.0, P < 0.001) during the follow-up. In both RAND-36 and EORTC-C30 surveys, decline was found in physical and role functioning together with energy and emotional well-being domains. SWAL-QOL showed poor swallowing-related QoL in both assessments. Conclusion: We found a significant decline in QoL during a 5-year follow-up after free flap surgery for cancer of the head and neck

Medical complications and outcome after endovascular therapy for acute ischemic stroke

Abstract Aim: Endovascular therapy (EVT) in acute stroke is an effective but invasive treatment which is frequently followed by various complications. The aim of the present study was to examine the rate of medical complications and other adverse events following EVT. Methods: Retrospective single-center study of 380 consecutive stroke patients who received EVT between the years 2015–2019. Results: A total of 234 (61.6%) patients had at least one recorded medical complication. The most common complication was pneumonia in 154 (40.5%) patients, followed by acute cardiac insufficiency in 134 (35.3%), and myocardial infarction in 22 (5.8%) patients. In multivariate analysis, the need for general anesthesia (OR 3.8 (1.9–7.7)), Charlson Comorbidity Index >3 (OR 1.3 (1.1–1.5)), male gender (1.9 (1.1–1.3)) and high National Institutes of Health Stroke Scale (NIHSS) score at admission (1.1 (1.0–1.2)) were associated with medical complications. Conclusion: Medical complications are common among unselected stroke patients undergoing EVT. Both comorbidity and stroke severity have an influence on medical complications. Early recognition of complications is essential, because vast majority of patients encountering medical complications have a poor short-term outcome

Outcomes in patients requiring intensive care unit (ICU) admission after emergency laparotomy:a retrospective study

Abstract Purpose: Outcomes after emergency laparotomy (EL) are poor. These patients are often admitted to an intensive care unit (ICU). This study explored outcomes in patients who were admitted to an ICU within 48 h after EL. Materials and Methods: This retrospective single-center registry study included all patients over 16 years of age that underwent an EL and were admitted to an ICU within 48 h after surgery in Oulu University Hospital, Finland between January 2005 and May 2015. Survival was followed until the end of 2019. Results: We included 525 patients. Hospital mortality was 13.3%, 30-day mortality was 17.3%, 90-day mortality was 24.2%, 1-year mortality was 33.0%, and 5-year mortality was 59.4%. Survivors were younger (57 [45–70] years) than the non-survivors (73 [62–80] years; p < .001). According to the Cox regression model, death during the follow-up was associated with age, APACHE II-score, lower postoperative CRP levels and platelet count of the first postoperative day, and the admission from the post-anesthesia care unit (PACU) to the ICU instead of direct ICU admission. Conclusion: Age, high APACHE II-score, low CRP and platelet count, and admission from the PACU to the ICU associated with mortality after EL in patients admitted to an ICU within 48 h after EL