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English summaryPeer reviewe

Pharmacological Preconditioning with Diazoxide in the Experimental Hypothermic Circulatory Arrest Model

Background: Hypothermic circulatory arrest includes a remarkable risk for neurological injury. Diazoxide, a mitochondrial adenosine triphosphate-dependent potassium ion (K+ATP) channel opener, is known to have cardioprotective effects. We assessed its efficacy in preventing ischemic injury in a clinically relevant animal model. Methods: Eighteen piglets were randomized into a diazoxide group (n = 9) and a control group (n = 9). Animals underwent 60 minutes of hypothermic circulatory arrest at 18 degrees C. Diazoxide (5 mg/kg + 10 mL NaOH + 40 mL NaCl) was infused during the cooling phase. Metabolic and hemodynamic data were collected throughout the experiment. After 24-hour follow-up, whole brain, heart, and kidney biopsy specimens were collected for analysis. Results: Cerebellar Cytochrome-C and caspase-3 activation was higher in the control group (P = .02 and P = .016, respectively). Antioxidant activity tended to be higher in the diazoxide group (P = .099). Throughout the experiment, the oxygen consumption ratio was higher in the control animals (P-g = .04), as were the lactate levels (P-g = .02). Cardiac function tended to be better in diazoxide-treated animals. Conclusion: Diazoxide might confer neuroprotective effect as implied by the immunohistochemical analysis of the brain. Additionally, the circulatory effects of diazoxide were beneficial, supporting its neuroprotective effect.Peer reviewe

Comorbidity characteristics of multiple myeloma patients diagnosed in Finland 2005-2016

Multiple myeloma (MM) patients are predominantly elderly with comorbidities that have an impact on patient mortality and treatment decisions. We previously reported the patient characteristics and overall survival outcomes of the Finnish MM cohort diagnosed between 2005 and 2016 in a nationwide retrospective registry study comprising 3,851 adults. Here, we report detailed comorbidity characteristics for this real-world Finnish MM population at cohort entry and during follow-up. Data on diagnoses and causes of death were obtained from Finnish healthcare data registries and interrogated using various multistate time-to-event models. In the year preceding MM diagnosis, comorbidities (as per Charlson Comorbidity Index definition) were recorded in 38.0% of the cohort, of which 27.9% presented with pre-existing cardiovascular disease (CVD) and 4.8% had suffered a major adverse cardiac event (MACE). At 2 years post-MM diagnosis, cumulative incidence for CVD and MACE more than doubled to 57.1% and 11.4%, respectively, and only 31.9% of the cohort remained CVD-free. Prevalent secondary malignancies were recorded in 16.8% of the patient population at MM diagnosis, with cumulative incidence increasing steadily to 27.5% at 2 years and 33% at 5 years post-diagnosis. The main cause of mortality attributed to MM, CVD, secondary malignancy, or other causes remained stable throughout the follow-up, at an average of 74.2%, 9.4%, 9.8%, and 6.5%, respectively. Prevalence of CVDs and secondary malignancies is high in Finnish patients at MM diagnosis, with older male patients suffering from higher MACE and mortality risk. Proper recording and management of comorbidities alongside novel treatments remain crucial for optimal MM management.Peer reviewe

Sepelvaltimoiden ohitusleikkaus 2020-luvulla

Vertaisarvioitu. English summary.• Sepelvaltimoiden ohitusleikkauksella voidaan helpottaa oireita ja vähentää kuoleman riskiä iskeemistä sepelvaltimotautia sairastavilla potilailla. • Ohitusleikkauksella saavutetaan erinomaiset pitkäaikaistulokset. Se on suositeltava revaskularisaatiomuoto varsinkin pitkälle edenneen ja vasenta päärunkoa ahtauttavan sepelvaltimotaudin hoidossa. • Diabeetikoilla ohitusleikkauksella saavutetaan pitkäaikaisempi hoitotulos kuin perkutaanisella ¬pallolaajennus- ja verkkoputkihoidolla. • Suomessa on merkittäviä alueellisia eroja sepelvaltimotaudin revaskularisaatiomuotojen käytössä.Peer reviewe

Sepelvaltimoiden ohitusleikkaus 2020-luvulla

• Sepelvaltimoiden ohitusleikkauksella voidaan helpottaa oireita ja vähentää kuoleman riskiä iskeemistä sepelvaltimotautia sairastavilla potilailla.• Ohitusleikkauksella saavutetaan erinomaiset pitkäaikaistulokset. Se on suositeltava revaskularisaatiomuoto varsinkin pitkälle edenneen ja vasenta päärunkoa ahtauttavan sepelvaltimotaudin hoidossa.• Diabeetikoilla ohitusleikkauksella saavutetaan pitkäaikaisempi hoitotulos kuin perkutaanisella ­pallolaajennus- ja verkkoputkihoidolla.• Suomessa on merkittäviä alueellisia eroja sepelvaltimotaudin revaskularisaatiomuotojen käytössä.</p

Exploring effects of remote ischemic preconditioning in a pig model of hypothermic circulatory arrest

Objectives. During aortic and cardiac surgery, risks for mortality and morbidity are inevitable. Surgical setups involving deep hypothermic circulatory arrest (DHCA) are effective to achieve organ protection against ischemic injury. The aim of this study was to identify humoural factors mediating additive protective effects of remote ischemic preconditioning (RIPC) in a porcine model of DHCA. Design. Twenty-two pigs were randomized into the RIPC group (n=11) and the control group (n=11). The RIPC group underwent four 5-minute hind limb ischemia-reperfusion cycles prior to cardiopulmonary bypass and DHCA. All animals underwent identical surgical procedures including 60min DHCA at 18 degrees C. Blood samples were collected from vena cava and sagittal sinus at several time points. After the 8-hour follow-up period, the brain, heart, and kidney tissue samples were collected for tissue analyses. Results. Serum levels of brain damage marker S100B recovered faster in the RIPC group, after 4hours of the arrest, (pPeer reviewe

The N-methyl-D -aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: A study in the chronic porcine model

AbstractBackground: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present study was to determine the potential efficacy of memantine, an N -methyl-D -aspartate receptor antagonist, to mitigate cerebral injury after hypothermic circulatory arrest. Methods: Twenty pigs (23-33 kg) were randomly assigned to receive memantine (5 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest at 20°C. Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. The intracerebral concentrations of glucose, lactate, glutamate, and glycerol were measured by means of enzymatic methods on a microdialysis analyzer. Daily behavioral assessment was performed until the animals died or were put to death on day 7. Histologic analysis of the brain was carried out in all animals. Results: In the memantine group, 5 of 10 animals survived 7 days compared with 9 of 10 in the placebo group. The median behavioral score at day 7 was 3.5 in the memantine group and 7.5 in the placebo group (P >.2). Among the surviving animals, medians were 9.0 and 8.0 on day 7 (P >.2), respectively. The medians of recovered electroencephalographic bursts were equal in both groups. The median of total histopathologic score was 16 in the memantine group and 14 in the placebo group (P >.2). There was a negative correlation between glutamate levels and electroencephalographic burst recovery (τ = –0.377, P =.043). A positive correlation was found between the highest individual glutamate value and histopathologic score (τ = 0.336, P =.045). Conclusions: The present study demonstrates that memantine has no neuroprotective effect after hypothermic circulatory arrest in the pig. In addition, we have shown the accuracy of cerebral glutamate measurements to predict histopathologic injury after hypothermic ischemia. (J Thorac Cardiovasc Surg 2001;121:957-70