European review for medical and pharmacological sciences最新文献

Osteoarthritis (OA) is a chronic and progressive degenerative disease that affects joint structures, such as the hips, knees, and hands, involving the articular cartilage, subchondral bone, ligaments, capsule, and synovium. OA is characterized by a progressive degeneration of the joint structures, resulting in pain and decreased quality of life. Local and systemic risk factors pave the way for OA development. Different phenotypes may be identified, but three main molecular mechanisms define the endotypes: the bone-driven endotype, the synovitis-driven endotype, and the cartilage-driven endotype. The hallmark of OA pathophysiology involves more than just mechanical degradation; it includes the release of pro-inflammatory mediators, such as interleukins and TNF-α, which elucidates the significant roles of metabolic syndrome, diabetes, and cellular senescence in its development. OA is distinguished by a clinical presentation that varies significantly between people and is marked by pain, stiffness, and functional impairments. The clinical course can be split into Pre-OA, Early OA, Evident OA, and End-Stage. Depending on the stage of the disease, OA diagnosis frequently necessitates a complex strategy that combines clinical evaluation to detect joint tenderness, range of motion, and joint swelling or abnormalities, medical history assessment, imaging modalities, and laboratory investigations. There is no known treatment for OA, and different therapies are usually evaluated based on the stage of the disease to minimize pain and stiffness while maintaining joint function. Treatments are divided into the reduction of modifiable risk factors, pharmacologic therapies, rehabilitation, complementary therapies, interventional pain procedures, and surgery. OA clinical heterogeneity underlines the importance of prevention, early diagnosis, and identifying the phenotype and endotype to tailor the treatment.

Objective: Despite the wide use of ziconotide in the USA for treating refractory cancer- and noncancer-related pain, this agent is little used in Europe, even if licensed by the European Medicines Agency (EMA). The reason could be attributed to the high, fixed starting dose required for ziconotide, as stated in the EMA Summary of Product Characteristics (SmPC). This dosage recommendation is based on the results of pivotal clinical studies of ziconotide, which utilized aggressive titration schedules. Thus, a reappraisal of the available evidence, as well as a reflection on real-life clinical experiences, might be useful to identify practice adjustments to improve the clinical application of ziconotide in the European scenario. In line with this need, this paper reports some clinical experiences of patients with chronic pain treated with ziconotide intrathecal (IT) therapy in Italy, particularly focusing on long-term treatment to further characterize and improve the use of this agent in real practice. Moreover, a literature review of the available data on the effectiveness and safety of IT ziconotide is provided.

Case series: Collected clinical experiences suggested that the use of IT ziconotide represents a valuable option, particularly in cases where other treatments have been ineffective or poorly tolerated. Ziconotide was shown to not cause severe side effects in the long-term treatment, leading to a constant pain relief effect at stable doses, without adverse events that caused therapy interruption. The overall constant ziconotide dosages also suggest the absence of a tolerance effect. In parallel, the evidence in the literature aligns with real-world evidence and further supports the use of IT ziconotide as an important option for the management of chronic pain.

Conclusions: IT ziconotide represents a valuable addition to the armamentarium of pain management strategies, offering hope for improved quality of life for patients suffering from chronic, treatment-resistant pain. Continued research and clinical experience will further elucidate its optimal use and role in comprehensive pain care.

Objective: A metabolism score for visceral fat (METS-VF) is an innovative method to access abdominal fat and visceral fat. So far, the relationship between the METS-VF index and chronic obstructive pulmonary disease (COPD) has remained unclear. We investigated the relationship between the METS-VF index and COPD prevalence utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018.

Patients and methods: A binary logistic regression analysis was performed using NHANES 2007-2018 data to assess the relationship between the METS-VF index and COPD prevalence. The relationship was verified by fitted smooth curves, generalized additive models, threshold effect analyses, subgroup analyses, and sensitivity analyses.

Results: In total, 7,680 subjects were recruited for the study, including 772 self-reported having COPD. The METS-VF index was positively related to COPD prevalence when adjusted for all covariates. The METS-VF index was classified by quartiles, and participants who scored highest on METS-VF were at a greater risk of COPD than those who scored lowest. According to a threshold effect analysis, the METS-VF index was negatively correlated with COPD prevalence with a METS-VF index <7.00, without statistical significance. Once the METS-VF index exceeded 7.00, there was a robust positive correlation between the METS-VF index and COPD prevalence. In the analysis of subgroups, the METS-VF index was positively correlated with COPD prevalence among subjects who were male, aged 40-59, and without asthma or hypertension. The results were robust in sensitivity analyses. METS-VF showed a significantly better diagnostic value for COPD than Body Mass Index (BMI).

Conclusions: The METS-VF index has a non-linear and positive correlation with COPD prevalence in the middle-aged and elderly American population.

Objective: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are a new class of drugs that lower blood glucose and reduce mortality in heart failure patients with reduced ejection fraction (HFrEF). They also have antioxidant effects. The exact mechanism of SGLT-2i is unknown. This study investigated the effects of SGLT-2i on asprosin, matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP-1) concentrations and echocardiographic measurements of strain in the left heart chamber.

Patients and methods: This prospective follow-up study included 56 patients with HFrEF and diabetes mellitus (DM) who did not initially receive SGLT-2 inhibitors. The control group consisted of 30 healthy individuals. Patients with HFrEF were administered either empagliflozin (n=28) or dapagliflozin (n=28) in addition to their treatment. The patient group was evaluated for left ventricular global longitudinal strain (LVGLS), left atrial (LA) strain, and LA volumes at the beginning and third month of the study. The control group had blood collected once, while the patient group had it twice: at the start of the trial, on the same day as the echocardiographic evaluation, and at the end of the third month after starting an SGLT-2i. Serum levels of asprosin, MMP-1 and TIMP-1 were assessed.

Results: LVGLS increased significantly in HFrEF patients at the third-month assessment compared to baseline (-8.6±2.3% vs. -9±2.5%, respectively; p<0.001), but there was no significant difference in LVEF (p=0.593). A substantial increase was observed in the left atrial ejection fraction (LAEF) compared to baseline values (36.3±9.4% vs. 42.1±8.7%, respectively; p<0.001), driven by a reduction in minimal LA volume [32.5 (19-96) ml vs. 32 (20-86) ml, respectively; p=0.018]. Compared to baseline evaluation, LA reservoir [13 (6-25) vs. 16.5 (2-26), respectively; p<0.001] and contraction strain (7.7±4.3 vs. 9.4±5.6, respectively; p=0.014) values were also enhanced at the third month. Between the baseline and the 3rd month, the patient group's LA conduit strain (p=0.122) and LA maximum volume (p=0.716) remained unchanged. Serum asprosin significantly increased (11.7±5.1 ng/mL vs. 14±9.4 ng/mL, respectively; p=0.032); however, no statistically significant alteration was detected in MMP (p=0.278) and TIMP-1 levels (p=0.401).

Conclusions: SGLT-2i are associated with elevated levels of LVGLS, LAEF, LA contraction strain, and LA reservoir strain. SGLT-2i medications may improve plasma asprosin levels to boost energy metabolism, reduce oxidative stress and reactive oxygen radicals.

Objective: In pediatric patients, femoral neck fracture is a relatively rare injury with a high complication rate despite proper diagnosis and treatment. Fixation of femoral neck fractures is usually performed with screws placed along the neck axis. In this study, we aim to compare two different implants and methods in terms of biomechanics.

Materials and methods: Twenty-eight right-left fresh femur bones of 6-month-old male Ovis aries lambs grown on the same farm were used. Bones were randomly divided into 4 groups (n=7). In group 1, the Delbet type III femoral neck fracture model was fixed with two 4.5 mm cannulated screws, one screw crossing the physis. In group 2, two 4.5 mm cannulated screws, which did not cross the physis, were used. In group 3, Delbet type III femoral neck fracture model was fixed with a 3.5 mm proximal femoral anatomical plate and five screws, one screw crossing the physis. Finally, in group 4, Delbet type III femoral neck fracture model was fixed with one 3.5 mm proximal femoral anatomical plate and five screws that did not exceed the physis.

Results: Biomechanical tests were performed using a Zwick/Roell AllroundLine 100 kN device. While axial failure burden (F = 6.819, p<.05, d = .46) and axial stiffness (F = 3.576, p<.05, d = .30) have been found to be significantly different between the independent treatment groups, axial failure displacement (F = .622, p>.05) and axial failure energy (F = .727, p>.05) have been found not to be significant between the independent groups. The effect sizes of the axial failure load and axial stiffness variables were 0.46 and 0.30, respectively, suggesting a moderate clinical effect. The highest axial failure load was recorded in group 3, while the smallest load was recorded in group 2. Similarly, the axial stiffness level in group 3 was statistically higher than the axial stiffness measurement recorded in group 2, p<.05.

Conclusions: Consequently, we found that the biomechanical fixation success was the highest with a 3.5 mm proximal femoral anatomical plate, a 3.5 mm locking screw crossing the physis, and five 3.5 mm screws.

Objective: Isorhamnetin, a naturally occurring flavonoid compound, holds paramount importance as a primary constituent within several medicinal plants, exhibiting profound pharmacological significance. The aim of this study is to investigate the pain-relieving attributes of isorhamnetin in murine models through both formalin-induced pain and diabetic neuropathy scenarios.

Materials and methods: To achieve our objective, isorhamnetin was orally administered to mice at varying dosage levels (10 to 100 mg/kg). Pain-related behaviors were assessed using the formalin test during its secondary phase. Additionally, the potential pain-alleviating effect of isorhamnetin was evaluated in a diabetic neuropathy model induced by streptozotocin. Additionally, we carried out advanced interventions using naloxone, which is a well-known antagonist of opioid receptors, yohimbine, which blocks α2-adrenergic receptors, and methysergide, which inhibits serotonergic receptors, during the formalin test.

Results: The oral intake of isorhamnetin showed a decrease in behaviors associated with pain that was proportional to the dose observed during the second phase of the formalin test when induced by formalin. In the diabetic neuropathy model, isorhamnetin administration effectively reversed the reduced pain threshold observed. Notably, naloxone, the opioid receptor antagonist, effectively counteracted the pain-relieving effect produced by isorhamnetin in the formalin test, whereas yohimbine and methysergide did not yield similar outcomes. Isorhamnetin also led to a reduction in elevated spinal cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels triggered by formalin, with this effect reversed by pre-treatment with naloxone. The compound also suppressed heightened spinal phosphorylated CREB (p-CREB) levels caused by diabetic neuropathy.

Conclusions: This research determined that isorhamnetin has notable abilities to relieve pain in models of formalin-induced pain and diabetic neuropathy. The pain-relieving mechanism of isorhamnetin in the formalin-induced pain model seems to be connected to the activation of spinal opioid receptors and the adjustment of CREB protein amounts. This insight improves our knowledge of how isorhamnetin could be used therapeutically to treat pain conditions stemming from formalin-induced pain and diabetic neuropathy.

Background: Bite injuries, particularly those involving the hands, present a significant medico-legal challenge, often leading to complications and frequent emergency department visits. Dog and cat bites, especially among children, are major contributors to infections due to the complex anatomy of the hand, which predisposes it to severe infections even from minor bites. Capnocytophaga canimorsus, found in the oral cavity of dogs and cats, is particularly concerning due to its potential to cause severe infections. Prompt and appropriate treatment is essential to mitigate these risks. Managing such injuries poses significant challenges, necessitating clear guidelines for reporting and safety measures. This article highlights the urgent need for additional research, support, and education, particularly focusing on children, along with the development of international guidelines to improve outcomes for patients.

Case report: A case study of a sixteen-year-old girl who had her left forearm amputated due to a rottweiler bite is presented. Despite initial attempts at replantation, complications led to the decision for amputation.

Conclusions: This case underscores the challenges in managing severe dog bite injuries, emphasizing the importance of prompt assessment, thorough debridement, and proper wound management to minimize complications. Additionally, psychological evaluation and treatment are crucial for patients and parents following such traumatic events. From a medical standpoint, this case highlights the importance of monitoring inflammatory markers, appropriate surgical priorities, and the need for psychological support. Prevention of dog bites is crucial, requiring increased awareness among public authorities and dog owners. Clear guidelines for reporting dog bites are essential, but further research is needed to improve their comprehensiveness and effectiveness.

Objective: The study compared the impact of unfractionated heparin (UFH) administered via two routes (infusion and subcutaneous injection) on heparin-binding protein (HBP) and plasminogen activator inhibitor-1 (PAI-1) levels in critically ill sepsis patients.

Patients and methods: Forty critically ill sepsis patients were randomly assigned to receive either a low-dose intravenous infusion of UFH (500 units/hour) or subcutaneous UFH (5,000 units/8 hours) for seven days. HBP and PAI-1 were measured at baseline and on days one, two, and seven.

Results: Intravenous administration of UFH showed a significant reduction in percentage change of HBP compared to subcutaneous administration on days one [(-35% vs. -13%, p = 0.03*) (*indicates a significant result *p < 0.05, relative to the subcutaneous group)] and seven (-62% vs. -39%, p = 0.02*). Also, the percentage change of PAI-1 was significantly reduced in the infusion group compared to the subcutaneous group on days one (-28% vs. -3%, p = 0.008*), two (-42% vs. -3%, p = 0.001*), and seven (-62% vs. 27%, p = 0.001*), respectively. Furthermore, a significant improvement in the 14-day survival was observed in the infusion group compared to the subcutaneous group (p = 0.008*).

Conclusions: Intravenous infusion was the route of choice for UFH administration in critically ill septic patients, with a promising effect on HBP, PAI-1, and survival.

Objective: Greater occipital nerve (GON) blockade injections can be used to prevent episodic and chronic cluster headaches. In recent studies, prophylactic treatment has been used in addition to the GON blockade. In this study, we aimed to elucidate the effect of GON blockade on the attack frequency, pain intensity, and duration in patients diagnosed with chronic cluster headaches.

Patients and methods: The demographic characteristics of 30 patients who received GON blockade along with acute attack treatment, short- and long-term prophylactic treatment for cluster headache, and 24 patients who received only acute attack treatment, short- and long-term prophylactic treatment, before blockade treatment, in the 1st week and 1st month after blockade were investigated. Attack frequency, attack duration, and visual analog scale (VAS) variables were compared.

Results: We evaluated the VAS score, daily attack frequency, and duration of pain attacks after repeated GON blockade and found a statistically significant difference in the VAS score, daily attack frequency, duration of pain attacks, average values of the treatment, and time interaction of pain intensity in the group in which GON blockade was applied in the 1st week and 1st month compared to the pre-treatment period (p<0.01), (p<0.01), (p=0.044).

Conclusions: Regarding the outcomes of this research, GON blockade provided significant improvement in pain frequency, attack duration, and VAS score in the period from attack treatment to the start of long-term prophylaxis treatment and one month after treatment, without the need to switch to different prophylaxis treatments. Therefore, GON blockade may be a preferable and reliable treatment option.

Objective: The study aims to show the efficacy/effectiveness and safety of vaccinations in patients with multiple sclerosis.

Materials and methods: This systematic review was conducted following the guidelines of the Cochrane Collaboration and the meta-analysis of observational studies in epidemiology (MOOSE).

Results: At the end of the review process, 133 studies were included; the bibliographic search was conducted on PubMed/Medline and Scopus, combining free text and words.

Conclusions: In general, vaccinations do not seem to aggravate multiple sclerosis (MS) or increase the probability of relapse, particularly for inactivated vaccines and, in general, for the rest of the vaccines. However, it is advisable, especially for vaccines with a live attenuated virus, to carefully evaluate the risks and benefits of these vaccinations; as regards the effectiveness in relation to the drug taken, there is great variability in response. In particular, vaccinations are less effective in patients undergoing therapy with anti-CD20 and S1P modulators. At the same time, a small response is likely to be better than none. Whenever possible, vaccinations should be offered and recommended to patients with multiple sclerosis.