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Magyar Sebeszet Dec 2023Egy 44 éves férfi betegnél endokarditisz talaján kialakult súlyos aortabillentyű-elégtelenség tett szükségessé szívsebészeti beavatkozást. A kevesebb mint...
ESETISMERTETÉS
Egy 44 éves férfi betegnél endokarditisz talaján kialakult súlyos aortabillentyű-elégtelenség tett szükségessé szívsebészeti beavatkozást. A kevesebb mint egy év alatt bekövetkezett többszöri trombotikus esemény felvetette antifoszfolipid szindróma lehetőségét. A lupus antikoaguláns pozitivitás és az említett klinikai kép ezt igazolta.
MEGBESZÉLÉS
Betegünk fiatal életkora és a biológiai műbillentyű korlátozott élettartama ellenére biológiai műbillentyű beültetése mellett döntöttünk. Választásunkat azzal indokoljuk, hogy tanulmányok bizonyítják antifoszfolipid szindrómás betegeknél a mechanikus műbillentyűvel összefüggésbe hozható thromboembolia viszonylag gyakori előfordulását. A műtétet szövődménymentesen elvégeztük, aktivált parciális thromboplastin idővel kontrollált Na-heparin korai adása mellett állítottuk be az orális antikoaguláns terápiát 3,0 INR célértékkel a műtét utáni ötödik napra. A műtét során eltávolított billentyűből korokozó nem tenyészett ki. A kórszövettani vizsgálat abakteriális endokarditiszt véleményezett, nem kizárva a korábbi fertőzést. Biológiai műbillentyű implantáció után három hónapig ajánlott aszpirin vagy K-vitamin antagonista adása, betegünk esetében viszont élethosszig tartó antikoaguláns kezelés szükséges, tekintettel rendszerbetegségére.
KÖVETKEZTETÉS
Halmozódó tromboembóliás események kapcsán gondolni kell antifoszfolipid szindrómára, mely igazolása adott esetben meghatározhatja a választható műbillentyű fajtáját. Az ajánlások legtöbbször csak általánosságban fedik le a ritka társbetegségeket, ezért a kapcsolódó szakirodalom áttekintése is szükséges az optimális, betegre szabott döntéshez.
Topics: Humans; Candy; Heparin; Mentha; Thromboplastin; Vitamin K
PubMed: 38175209
DOI: 10.1556/1046.2023.40002 -
Molecules (Basel, Switzerland) Mar 2024Solid-phase peptide synthesis (SPPS) is the preferred strategy for synthesizing most peptides for research purposes and on a multi-kilogram scale. One key to the success... (Review)
Review
Solid-phase peptide synthesis (SPPS) is the preferred strategy for synthesizing most peptides for research purposes and on a multi-kilogram scale. One key to the success of SPPS is the continual evolution and improvement of the original method proposed by Merrifield. Over the years, this approach has been enhanced with the introduction of new solid supports, protecting groups for amino acids, coupling reagents, and other tools. One of these improvements is the use of the so-called "safety-catch" linkers/resins. The linker is understood as the moiety that links the peptide to the solid support and protects the C-terminal carboxylic group. The "safety-catch" concept relies on linkers that are totally stable under the conditions needed for both α-amino and side-chain deprotection that, at the end of synthesis, can be made labile to one of those conditions by a simple chemical reaction (e.g., an alkylation). This unique characteristic enables the simultaneous use of two primary protecting strategies: tert-butoxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). Ultimately, at the end of synthesis, either acids (which are incompatible with Boc) or bases (which are incompatible with Fmoc) can be employed to cleave the peptide from the resin. This review focuses on the most significant "safety-catch" linkers.
Topics: Solid-Phase Synthesis Techniques; Alkylation; Amino Acids; Antifibrinolytic Agents; Resins, Plant; Peptides
PubMed: 38611709
DOI: 10.3390/molecules29071429 -
Nutrients Nov 2023Vitamin K (VK), a fat-soluble vitamin, is essential for the clotting of blood because of its role in the production of clotting factors in the liver. Moreover,... (Review)
Review
Vitamin K (VK), a fat-soluble vitamin, is essential for the clotting of blood because of its role in the production of clotting factors in the liver. Moreover, researchers continue to explore the role of VK as an emerging novel bioactive molecule with the potential function of improving bone health. This review focuses on the effects of VK on bone health and related mechanisms, covering VK research history, homologous analogs, dietary sources, bioavailability, recommended intake, and deficiency. The information summarized here could contribute to the basic and clinical research on VK as a natural dietary additive and drug candidate for bone health. Future research is needed to extend the dietary VK database and explore the pharmacological safety of VK and factors affecting VK bioavailability to provide more support for the bone health benefits of VK through more clinical trials.
Topics: Humans; Vitamin K; Vitamin K Deficiency; Bone and Bones; Blood Coagulation; Vitamins; Vitamin K 2; Vitamin K 1
PubMed: 38068793
DOI: 10.3390/nu15234935 -
Physiology & Behavior Oct 2023Vitamin K2/ Menaquinones produced predominantly by the gut microbiome improve bone health and prevent coronary calcification. The central nervous system has been linked...
Vitamin K2/ Menaquinones produced predominantly by the gut microbiome improve bone health and prevent coronary calcification. The central nervous system has been linked with gut microbiota via the gut-brain axis and is strongly associated with psychiatric conditions. In the present study, we show the role of Vitamin K2 (MK-7) in gut dysbiosis-associated cognitive decline. Gut dysbiosis was induced in mice by administering Ampicillin (250 mg/kg twice a day orally) for 14 days and Vitamin K2 (0.05 mg/kg) for 21 days with or without antibiotic treatment and altered gene expression profile of intestinal microbes determined. This was followed by behavioural studies to determine cognitive changes. The behavioural observations are then correlated with proinflammatory, oxidative, and brain and intestinal histopathological changes in antibiotic-treated animals with or without vitamin K2 administration. With the use of antibiotics, Lactobacillus, Bifidobacterium, Firmicutes, and Clostridium's relative abundance reduced. When vitamin K2 was added to the medication, their levels were restored. Cognitive impairment was observed in behavioural trials in the antibiotic group, but this drop was restored in mice given both an antibiotic and vitamin K. Myeloperoxidase levels in the colon and brain increased due to gut dysbiosis, which vitamin K2 prevented. The acetylcholine esterase and oxidative stress markers brought on by antibiotics were also decreased by vitamin K2. Additionally, vitamin K2 guarded against alterations in intestine ultrastructure brought on by antibiotic use and preserved hippocampus neurons. So, it can be concluded that vitamin K2 improved cognitive skills, avoided hippocampus neuronal damage from antibiotics, and lowered intestine and brain inflammation and oxidative stress.
Topics: Mice; Animals; Vitamin K 2; Neuroprotective Agents; Dysbiosis; Anti-Bacterial Agents; Cognitive Dysfunction
PubMed: 37257737
DOI: 10.1016/j.physbeh.2023.114252 -
Journal of Orthopaedic Surgery and... Aug 2023With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function, but is often associated with massive blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip or knee arthroplasty. However, the optimal dose of TXA administration remains controversial. Therefore, we performed a meta-analysis combining data from 5 trials comparing the efficacy and safety of one fixed dose of 1 g intravenously administered TXA with two doses of 1 g each administered intravenously for hip or knee arthroplasty.
METHODS
PubMed, Medline, Embase, Web of Science, and The Cochrane Library were searched from January 2000 to February 2023. Our meta-analysis included randomized controlled trials and cohort studies comparing the efficacy and safety of different doses of intravenous TXA (IV-TXA) for THA or TKA. The observation endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, incidence of deep venous thrombosis (DVT), and incidence of pulmonary embolism (PE). Meta-analysis was performed according to Cochrane's guidelines and PRISMA statement. The Danish RevMan5.3 software was used for data merging.
RESULTS
Five cohort studies involving 5542 patients met the inclusion criteria. Our meta-analysis showed that the two groups were significantly higher in total blood loss (mean difference (MD) = - 65.60, 95% confidence interval (CI) [- 131.46, 0.26], P = 0.05); blood transfusion rate (risk difference (RD) = 0.00, 95% CI [- 0.01, 0.02], P = 0.55); postoperative hemoglobin (MD = 0.02, 95% CI [- 0.09, 0.13], P = 0.31); postoperative hospital stay days (MD = - 0.13), 95% CI [- 0.35, 0.09], P = 0.25); DVT (RD = 0.00, 95% CI [- 0.00, 0.01], P = 0.67); PE (RD = 0.00, 95% CI [- 0.01, 0.00], P = 0.79). There was some inherent heterogeneity due to variance in sample size across each major study.
CONCLUSION
1 dose of 1 g and 2 doses of 1 g IV-TXA each time have similar effects on reducing blood loss, blood transfusion rate, postoperative hemoglobin level, and postoperative hospital stay after TKA or THA, without increasing the risk of postoperative complications risk. For patients at high risk of thromboembolic events, one dose of 1 g TXA throughout surgery may be preferred. However, higher-quality RCT is needed to explore the optimal protocol dose to recommend the widespread use of TXA in total joint arthroplasty. Trial registration We conducted literature selection, eligibility criteria evaluation, data extraction and analysis on the research program registered in Prospero (CRD42023405387) on March 16, 2023.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Venous Thrombosis; Blood Loss, Surgical; Arthroplasty, Replacement, Hip; Administration, Intravenous; Pulmonary Embolism; Hemoglobins
PubMed: 37563702
DOI: 10.1186/s13018-023-03929-9 -
Current Opinion in Anaesthesiology Apr 2024Tranexamic acid is routinely used as part of the management of traumatic bleeding. The dose recommendation in trauma was extrapolated from other clinical settings and... (Review)
Review
PURPOSE OF REVIEW
Tranexamic acid is routinely used as part of the management of traumatic bleeding. The dose recommendation in trauma was extrapolated from other clinical settings and the results of pragmatic randomized trials rather than pharmaco-kinetic and -dynamic evaluations. The review addresses current evidence on dosing of tranexamic acid in traumatized patients with a focus on efficacy, safety and risk-benefit profile.
RECENT FINDINGS
A majority, but not all, of existing randomized clinical trials reports a reduction in mortality and/or blood loss with tranexamic acid administration. Increasing dose above the general recommendation (1 g bolus + 1 g infusion/8 h intravenously) has not been shown to further increase efficacy and could potentially increase side effects.
SUMMARY
The benefit of tranexamic acid as adjuvant therapy in the management of bleeding trauma patients on mortality and transfusion requirements is clear and well documented, being most effective if given early and to patients with clinical signs of hemorrhagic shock. Recent reports suggest that in some patients presenting with a shutdown of their fibrinolytic pathway the administration of tranexamic acid could be associated with an increased risk of thromboembolic events and poor outcomes. A more personalized approach based on bedside assessment of fibrinolytic activation and pharmacokinetic-based dose regimen should be developed moving forward.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Hemorrhage; Blood Transfusion
PubMed: 38390911
DOI: 10.1097/ACO.0000000000001357 -
Annali Di Igiene : Medicina Preventiva... 2023Aging is a complex and gradual biological process that represents the major risk factor with respect to the development of chronic degenerative diseases, often...
BACKGROUND
Aging is a complex and gradual biological process that represents the major risk factor with respect to the development of chronic degenerative diseases, often associated with disability. Diet and nu-trition, coupled with proper physical activity have a significant impact on the health status of the elderly with a decreased risk of disease being indicative of successful aging. Musculoskeletal conditions such as osteoporosis and sarcopenia are the most frequently reported disorders among the elderly community.
METHODS
This study presents a systematic review of the literature on the potential benefits of several nutra-ceuticals in promoting healthy aging and in reducing the risk of chronic diseases in elderly individuals.
RESULTS
Dietary components including vitamins (vitamin C, B vitamin and vitamin K) flavonoids (e.g., quercetin, anthocyanins, and isoflavones), minerals (e.g., magnesium, zinc and potassium) and other nutrients such phytoestrogens, amino acids, and omega-3 fatty acids help in slowing the aging process, which ultimately results in increased lifespan and longevity.
CONCLUSIONS
This paper highlights the key nutrients and phytochemicals of nutraceutical importance for the healthy aging of the elderly population. Although the scientific literature provides evidences of therapeutic effectiveness of nutraceuticals, more in-depth clinical investigations are needed.
Topics: Aged; Humans; Healthy Aging; Anthocyanins; Dietary Supplements; Vitamins; Diet; Vitamin K
PubMed: 36515582
DOI: 10.7416/ai.2022.2552 -
No Shinkei Geka. Neurological Surgery Nov 2023To reduce the number of preventable trauma deaths(PTD), a standardized approach has been established with various training courses and guidelines such as the Japan...
To reduce the number of preventable trauma deaths(PTD), a standardized approach has been established with various training courses and guidelines such as the Japan Advanced Trauma Evaluation and Care and Guidelines for the Diagnosis and Treatment of Traumatic Brain Injury. To prevent PTD, initial treatment, including resuscitation, is crucial in the care of traumatic brain injury(TBI). The Japan Neurotrauma Data Bank recently reported that the number of patients with TBI is increasing. Patients on antithrombotic drugs are also increasing. Although the mortality rate is decreasing, the percentage of patients with favorable outcomes is also decreasing. Therefore, to prevent secondary brain injury, rapid and systematic assessment of physiological abnormalities and resuscitation using the ABCDE approach, diagnosis and treatment of impending D, administration of tranexamic acid(an antifibrinolytic drug), and timely administration of anticoagulant neutralizers are important.
Topics: Humans; Brain Injuries, Traumatic; Brain Injuries; Antifibrinolytic Agents; Tranexamic Acid; Japan
PubMed: 38011878
DOI: 10.11477/mf.1436204850 -
The Lancet. Global Health Aug 2023Worldwide, more than half a billion women of reproductive age are anaemic. Each year, about 70 000 women who give birth die from postpartum haemorrhage. Almost all... (Clinical Trial)
Clinical Trial
BACKGROUND
Worldwide, more than half a billion women of reproductive age are anaemic. Each year, about 70 000 women who give birth die from postpartum haemorrhage. Almost all deaths are in low-income or middle-income countries. We examined the association between anaemia and the risk of postpartum haemorrhage.
METHODS
We did a prospective cohort analysis of data from the World Maternal Antifibrinolytic-2 (WOMAN-2) trial. This trial enrols women with moderate or severe anaemia giving birth vaginally in hospitals in Pakistan, Nigeria, Tanzania, and Zambia. Moderate anaemia was defined as a haemoglobin concentration of 70-99 g/L and severe anaemia as less than 70 g/L. Hospitals in each country where anaemia in pregnancy is common were identified from a network established during previous obstetric trials. Women who were younger than 18 years without permission provided by a guardian, had a known tranexamic acid allergy, or developed postpartum haemorrhage before the umbilical cord was cut or clamped were excluded from the study. Prebirth haemoglobin, the exposure, was measured after hospital arrival and just before giving birth. Postpartum haemorrhage, the outcome, was defined in three ways: (1) clinical postpartum haemorrhage (estimated blood loss ≥500 mL or any blood loss sufficient to compromise haemodynamic stability); (2) WHO-defined postpartum haemorrhage (estimated blood loss of at least 500 mL); and (3) calculated postpartum haemorrhage (calculated estimated blood loss of ≥1000 mL). Calculated postpartum haemorrhage was estimated from the peripartum change in haemoglobin concentration and bodyweight. We used multivariable logistic regression to examine the association between haemoglobin and postpartum haemorrhage, adjusting for confounding factors.
FINDINGS
Of the 10 620 women recruited to the WOMAN-2 trial between Aug 24, 2019, and Nov 1, 2022, 10 561 (99·4%) had complete outcome data. 8751 (82·9%) of 10 561 women were recruited from hospitals in Pakistan, 837 (7·9%) from hospitals in Nigeria, 525 (5·0%) from hospitals in Tanzania, and 448 (4·2%) from hospitals in Zambia. The mean age was 27·1 years (SD 5·5) and mean prebirth haemoglobin was 80·7 g/L (11·8). Mean estimated blood loss was 301 mL (SD 183) for the 8791 (83·2%) women with moderate anaemia and 340 mL (288) for the 1770 (16·8%) women with severe anaemia. 742 (7·0%) women had clinical postpartum haemorrhage. The risk of clinical postpartum haemorrhage was 6·2% in women with moderate anaemia and 11·2% in women with severe anaemia. A 10 g/L reduction in prebirth haemoglobin increased the odds of clinical postpartum haemorrhage (adjusted odds ratio [aOR] 1·29 [95% CI 1·21-1·38]), WHO-defined postpartum haemorrhage (aOR 1·25 [1·16-1·36]), and calculated postpartum haemorrhage (aOR 1·23 [1·14-1·32]). 14 women died and 68 either died or had a near miss. Severe anaemia was associated with seven times higher odds of death or near miss (OR 7·25 [95% CI 4·45-11·80]) than was moderate anaemia.
INTERPRETATION
Anaemia is strongly associated with postpartum haemorrhage and the risk of death or near miss. Attention should be given to the prevention and treatment of anaemia in women of reproductive age.
FUNDING
The WOMAN-2 trial is funded by Wellcome and the Bill & Melinda Gates Foundation.
Topics: Adult; Female; Humans; Pregnancy; Anemia; Antifibrinolytic Agents; Cohort Studies; Hemoglobins; Postpartum Hemorrhage; Prospective Studies
PubMed: 37390833
DOI: 10.1016/S2214-109X(23)00245-0 -
Osteoarthritis and Cartilage Sep 2023The purpose of this study was to investigate the effect of age and oxidative stress on regulation of nuclear factor erythroid-2-related factor 2 (Nrf2) in young, old,...
OBJECTIVE
The purpose of this study was to investigate the effect of age and oxidative stress on regulation of nuclear factor erythroid-2-related factor 2 (Nrf2) in young, old, and osteoarthritic (OA) human articular chondrocytes.
DESIGN
Levels of Nrf2 in primary human chondrocytes isolated from young, old, and OA donors were measured by immunoblotting, qPCR, and immunohistochemistry. Effects on levels of Nrf2, antioxidant proteins regulated by Nrf2, as well as p65, and the anabolic response to insulin-like growth factor-1 (IGF-1) were evaluated after induction of oxidative stress with menadione, Nrf2 knockdown with siRNA, and/or Nrf2 activation with RTA-408.
RESULTS
Nrf2 protein levels were significantly lower in older adult chondrocytes (∼0.59 fold; p = 0.034) and OA chondrocytes (∼0.50 fold; p = 0.016) compared to younger cells. Menadione significantly increased Nrf2 protein levels in young chondrocytes by just under four-fold without changes in old chondrocytes. Nrf2 knockdown and activation differentially regulated levels of anti-oxidant proteins including sulfiredoxin and NAD(P)H quinone dehydrogenase 1. Nrf2 activation with RTA-408 also decreased basal p65 phosphorylation, increased aggrecan and type II collagen gene expression, and increased production of proteoglycans in OA chondrocytes treated with IGF-1.
CONCLUSIONS
Targeted therapeutic strategies aimed at maintaining Nrf2 activity could be useful in maintaining chondrocyte homeostasis through maintenance of intracellular antioxidant function and redox balance.
Topics: Aged; Humans; Antioxidants; Cartilage, Articular; Cells, Cultured; Chondrocytes; Homeostasis; Insulin-Like Growth Factor I; NF-E2-Related Factor 2; Osteoarthritis; Oxidative Stress; Vitamin K 3
PubMed: 37160250
DOI: 10.1016/j.joca.2023.05.004