Age of patient at the extraction of the third molar

The purpose of this study was to assess the age of patients at the time of extraction of third molars. Our data included all routine and surgical extractions of third molars (n = 8199 teeth) performed by general and specialist dentists of the public oral health services of the city of Helsinki over the period 2013-2014. Measurements included patient's age, gender, the identified third molar, the type of anaesthesia, the method of extraction, and the diagnosis at extraction. Patients' ages ranged from 10 to 99 years. We found significant differences between younger and older age groups: third molar extractions occurred more often for women than for men below the age of 30 years (P <0.001) and vice versa for patients older than 30. Extractions were more prevalent for the upper jaw (P <0.001), and surgical extractions were more common than routine extractions (P <0.001) below the age of 40 years, but the corresponding prevalences reversed after the age of 40 years. Diagnoses at extraction differed between younger and older patients. We conclude that the treatment pattern of third molars at public health services varies greatly over a lifetime, and that a greater variety exists than had been reported previously from oral and maxillofacial units.Peer reviewe

Grass silage for biorefinery – Separation efficiency and aerobic stability of silage and solid fraction

201

Gemtuzumab-Ozogamicin-Related Impaired Hemoglobin-Haptoglobin Scavenging as On-Target/Off-Tumor Toxicity of Anti-CD33 AML Therapy : A Report of Two Cases

Gemtuzumab-ozogamicin (GO) is a humanized anti-CD33 antibody, which is conjugated to a cytotoxic calicheamicin. It is used to treat acute myeloid leukemia (AML) in combination with chemotherapy. We describe here two GO-treated acute myeloid leukemia (AML) cases: both patients suffered from a toxic syndrome, which manifested as impaired hemoglobin-haptoglobin scavenging and accumulation of hemolysis-related products. Our observations and earlier reports indicated that the reaction was caused by GO-targeted destruction of CD33 + CD163+ monocytes/macrophages, which are responsible for the clearance of hemoglobin-haptoglobin complexes. The rise of plasma lactate dehydrogenase was an early sign of the reaction, and both patients had high levels of free plasma hemoglobin, but plasma haptoglobin and bilirubin levels were paradoxically normal. Symptoms included septic fever and abnormalities in cardiac tests and in the case of the first patient, severe neurological symptoms which required intensive care unit admittance. Therapeutic plasma exchanges supported the patients until the recovery of normal hematopoiesis. The symptoms may be easily confounded with infectious complications-related organ damage. Regarding the increasing use of gemtuzumab-ozogamicin and other emerging CD33-targeted cell therapies, we want to highlight this mostly unknown and probably underdiagnosed toxicity.Peer reviewe

Subsequent malignant neoplasms after primary hematological malignancy in adult patients

Patients with primary hematological malignancy (HM) are at an elevated risk of subsequent malignant neoplasms (SMNs), which is a common concern after treatment of primary cancer. We identified 45,533 patients aged ≥20 years and diagnosed with primary HM in Finland from 1992 to 2019 from the Finnish Cancer Registry and estimated standardized incidence ratios (SIR) and excess absolute risks per 1000 person-years (EAR) for SMNs. A total of 6076 SMNs were found (4604 solid and 1472 hematological SMNs). The SIRs were higher for hematological SMNs (SIR 4.9, 95% confidence interval [CI] 4.7–5.2) compared to solid SMNs (SIR 1.5, 95% CI 1.4–1.5). The SIRs for hematological SMNs were highest in the young HM patients aged 20–39 years (SIR 9.2, 95% CI 6.8–12.2 in males and SIR 10.5, 95% CI 7.2–14.7 in females) and decreased by age of first primary HM. However, EARs for hematological SMNs were highest in the older patients, aged 60–79 years at their first primary HM (EAR 5.7/1000 and 4.7/1000 in male and female patients, respectively). In conclusion, the incidence of both hematological and solid SMNs were increased in hematological cancer patients. The relative risk (SIR) was highest among younger HM patients with hematological SMNs. The absolute second cancer burden reflected by high EAR arises from solid malignancies in older patients. Our results accentuate the need for vigilance in the surveillance of HM patients.Peer reviewe

Enrichment of cancer-predisposing germline variants in adult and pediatric patients with acute lymphoblastic leukemia

Despite recent progress in acute lymphoblastic leukemia (ALL) therapies, a significant subset of adult and pediatric ALL patients has a dismal prognosis. Better understanding of leukemogenesis and recognition of germline genetic changes may provide new tools for treating patients. Given that hematopoietic stem cell transplantation, often from a family member, is a major form of treatment in ALL, acknowledging the possibility of hereditary predisposition is of special importance. Reports of comprehensive germline analyses performed in adult ALL patients are scarce. Aiming at fulfilling this gap of knowledge, we investigated variants in 93 genes predisposing to hematologic malignancies and 70 other cancer-predisposing genes from exome data obtained from 61 adult and 87 pediatric ALL patients. Our results show that pathogenic (P) or likely pathogenic (LP) germline variants in genes associated with predisposition to ALL or other cancers are prevalent in ALL patients: 8% of adults and 11% of children. Comparison of P/LP germline variants in patients to population-matched controls (gnomAD Finns) revealed a 2.6-fold enrichment in ALL cases (CI 95% 1.5-4.2, p = 0.00071). Acknowledging inherited factors is crucial, especially when considering hematopoietic stem cell transplantation and planning post-therapy follow-up. Harmful germline variants may also predispose patients to excessive toxicity potentially compromising the outcome. We propose integrating germline genetics into precise ALL patient care and providing families genetic counseling.Peer reviewe

A minor role of asparaginase in predisposing to cerebral venous thromboses in adult acute lymphoblastic leukemia patients

Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000. In the risk factor analyses for VTs we found a distinction of the characteristics of the patients acquiring CVT from those with other kinds of VTs or without thrombosis. In contrast to previous studies we were also able to compare the effects of asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs were diagnosed prior the administration of asparaginase which accentuates the role of other risk factors on the pathophysiology of CVT compared to truncal or central venous line (CVL) VTs in adult ALL patients

Truncating <em>NFKB1 </em>variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis

\ua9 2024 The AuthorsIn monogenic autoinflammatory diseases, mutations in genes regulating innate immune responses often lead to uncontrolled activation of inflammasome pathways or the type I interferon (IFN-I) response. We describe a mechanism of autoinflammation potentially predisposing patients to life-threatening necrotizing soft tissue inflammation. Six unrelated families are identified in which affected members present with necrotizing fasciitis or severe soft tissue inflammations. Exome sequencing reveals truncating monoallelic loss-of-function variants of nuclear factor κ light-chain enhancer of activated B cells (NFKB1) in affected patients. In patients’ macrophages and in NFKB1-variant-bearing THP-1 cells, activation increases both interleukin (IL)-1β secretion and IFN-I signaling. Truncation of NF-κB1 impairs autophagy, accompanied by the accumulation of reactive oxygen species and reduced degradation of inflammasome receptor nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3), and Toll/IL-1 receptor domain-containing adaptor protein inducing IFN-β (TRIF), thus leading to combined excessive inflammasome and IFN-I activity. Many of the patients respond to anti-inflammatory treatment, and targeting IL-1β and/or IFN-I signaling could represent a therapeutic approach for these patients

Ei merkittävää haittaa -periaatteen (DNSH) soveltaminen Suomen elpymis- ja palautumissuunnitelman hankkeissa

Tämä raportti esittelee lähestymistavan ja ohjeita DNSH-arviointiin Suomen elpymis- ja palautumissuunnitelman hankkeissa ja mahdollisissa muissa DNSH-arviointeja edellyttävissä hankkeissa. Euroopan unionin jäsenmaiden on laadittava jokaiselle elpymis- ja palautumissuunnitelman toimenpiteelle elvytystoimista mahdollisesti aiheutuvan haitan määrittelemiseksi ns. DNSH-arviointi (Do No Significant Harm). Elpymis- ja palautumissuunnitelmaan liittyy kestävän kasvun investointi- ja rahoitusohjelmia. DNSH-arvioinnissa rahoitusohjelmien vastuutahojen on varmistettava, että jokainen elpymis- ja palautumistukivälineestä rahoitettava hanke on DNSH-periaatteen mukainen kaikkien kuuden ympäristötavoitteen osalta: 1. ilmastonmuutoksen hillintä 2. ilmastonmuutokseen sopeutuminen 3. vesivarojen ja merten luonnonvarojen kestävä käyttö ja suojelu 4. siirtyminen kiertotalouteen 5. ympäristön pilaantumisen ehkäiseminen ja vähentäminen 6. biologisen monimuotoisuuden ja ekosysteemien suojelu ja ennallistaminen. Suomen ympäristökeskus on kehittänyt DNSH-arviointien ohjeistusta ja arviointien toteutuskaavioita erilaisten kestävän kasvun investointi- ja rahoitusohjelmista rahoitettavien hankehakujen tueksi ja taustamateriaaliksi rahoitusohjelmien vastuutahoille. Arviointimenetelmien kehittämisessä on kiinnitetty huomiota erityisesti Suomen kestävän kasvun ohjelmassa tunnistettuihin teollisuuden investointihankkeisiin sekä tutkimus-, kehittämis- ja innovaatiohankkeisiin. Suomen elpymis- ja palautumissuunnitelman hankkeiden lisäksi kehitettyjä arviointimenetelmiä voidaan soveltaen käyttää myös muissa DNSH-arviointeja edellyttävissä hankkeissa. Kehitettävien arviointimenetelmien käyttäjiä ovat rahoitusohjelmien vastuutahot, ensisijaisesti Business Finland, Suomen Akatemia, ympäristöministeriö ja työ- ja elinkeinoministeriö, ELY-keskukset sekä rahoitushakuja tekevien hankkeiden vastuutahot

Implementation of the DNSH principle for measures set out in Finland’s recovery and resilience plan

This report presents approaches and guidance for the DNSH assessment of projects in the Finnish recovery and resilience plan and other projects possibly requiring a DNSH assessment. Member States must provide a Do No Significant Harm (DNSH) assessment for each of the measures in their recovery and resilience plan. No action included in a recovery and resilience plan should cause significant harm to any of the six environmental objectives: 1. climate change mitigation 2. climate change adaptation 3. sustainable use and protection of water and marine resources 4. transition to a circular economy 5. prevention and control of air, water and soil pollution 6. protection and restoration of biodiversity and ecosystems. The Finnish Environment Institute, Syke, has developed guidance and methodologies for the DNSH assessment of funding applications under the Finnish program for sustainable growth. The developed methods and approaches are designed particularly for investment projects as well as research, development and innovation projects. To a large extent, the developed methodology can also be applied in the DNSH assessment of other types of projects. Users of the developed assessment methods are the bodies responsible for funding programs, especially, Business Finland, Academy of Finland, Ministry of the Environment, Ministry of Employment and the Economy, Centres for Economic Development, Transport and the Environment and those organizations applying for funding.Ei merkittävää haittaa -periaatteen (DNSH) soveltaminen Suomen elpymis- ja palautumissuunnitelman hankkeissa Tämä raportti esittelee lähestymistavan ja ohjeita DNSH-arviointiin Suomen elpymis- ja palautumissuunnitelman hankkeissa ja mahdollisissa muissa DNSH-arviointeja edellyttävissä hankkeissa. Euroopan unionin jäsenmaiden on laadittava jokaiselle elpymis- ja palautumissuunnitelman toimenpiteelle elvytystoimista mahdollisesti aiheutuvan haitan määrittelemiseksi ns. DNSH-arviointi (Do No Significant Harm). Elpymis- ja palautumissuunnitelmaan liittyy kestävän kasvun investointi- ja rahoitusohjelmia. DNSH-arvioinnissa rahoitusohjelmien vastuutahojen on varmistettava, että jokainen elpymis- ja palautumistukivälineestä rahoitettava hanke on DNSH-periaatteen mukainen kaikkien kuuden ympäristötavoitteen osalta: 1. ilmastonmuutoksen hillintä 2. ilmastonmuutokseen sopeutuminen 3. vesivarojen ja merten luonnonvarojen kestävä käyttö ja suojelu 4. siirtyminen kiertotalouteen 5. ympäristön pilaantumisen ehkäiseminen ja vähentäminen 6. biologisen monimuotoisuuden ja ekosysteemien suojelu ja ennallistaminen. Suomen ympäristökeskus on kehittänyt DNSH-arviointien ohjeistusta ja arviointien toteutuskaavioita erilaisten kestävän kasvun investointi- ja rahoitusohjelmista rahoitettavien hankehakujen tueksi ja taustamateriaaliksi rahoitusohjelmien vastuutahoille. Arviointimenetelmien kehittämisessä on kiinnitetty huomiota erityisesti Suomen kestävän kasvun ohjelmassa tunnistettuihin teollisuuden investointihankkeisiin sekä tutkimus-, kehittämis- ja innovaatiohankkeisiin. Suomen elpymis- ja palautumissuunnitelman hankkeiden lisäksi kehitettyjä arviointimenetelmiä voidaan soveltaen käyttää myös muissa DNSH-arviointeja edellyttävissä hankkeissa. Kehitettävien arviointimenetelmien käyttäjiä ovat rahoitusohjelmien vastuutahot, ensisijaisesti Business Finland, Suomen Akatemia, ympäristöministeriö ja työ- ja elinkeinoministeriö, ELY-keskukset sekä rahoitushakuja tekevien hankkeiden vastuutahot