Use of chloroprocaine in orthopedic day surgery: a brief report in a cohort of patients undergoing knee arthroscopy.

OBJECTIVE: Spinal anesthesia with local anesthetics is a viable alternative to general anesthesia in orthopedic surgery, and it is currently considered the standard of care for knee arthroscopy. The use of chloroprocaine may offer several potential advantages over other local anesthetics, including, above all, its rapid onset and short duration of action. The aim of the present retrospective study is to evaluate the post-surgical outcomes of patients who underwent knee arthroscopy using spinal anesthesia with chloroprocaine in an outpatient orthopedic setting. PATIENTS AND METHODS: Data from patients who underwent elective knee arthroscopy between January 2022 and December 2022 were collected for the present study. Spinal anesthesia with chloroprocaine 10 mg/mL was administered in the designated subarachnoid space (L3-L4 in the majority of patients). A dosage of 40 mg was used to obtain a satisfactory sensory and motor block. RESULTS: A total number of 302 patients met the inclusion criteria. No complications were reported during surgery in the present series of patients. None of the patients required bladder catheterization. In 84% of cases, the PADSS (Post-Anesthetic Discharge Scoring System) score at discharge was 10, whereas in 16% of cases, the PADSS score was 9. The mean time from anesthesia induction to first urination was 75±9.4 minutes, while the mean time from the anesthesia induction to the discharge from the hospital was 152±18.5 minutes. CONCLUSIONS: Spinal chloroprocaine for knee arthroscopy demonstrated a short motor block duration, resulting in a fast time to discharge. These limited data show that chloroprocaine may be safely and effectively applied in outpatient knee arthroscopy procedures. However, more studies, possibly with a randomized design, are required to confirm these findings.

[Deep venous thrombosis of the upper limb in a violin player: The "bow syndrome"]. / Thrombose veineuse profonde du membre supérieur chez une violoniste : « le syndrome de l'archet ¼.

BACKGROUND: Exercise-induced thrombosis is a rare cause of deep venous thrombosis (DVT) of the upper limb and usually affects young subjects without comorbid conditions. The diagnosis may be challenging. CASE REPORT: A 23-year-old female right-handed French teacher and amateur violin player presented with edema of the root of the right arm associated with erythrocyanosis of the extremity and collateral circulation of the shoulder. History taking revealed oral contraception and recent change in violin playing habits. D-dimers were negative. A second duplex-Doppler was required before visualization of a DVT in the right subclavian vein. The patient was given low-molecular-weight heparin alone, followed by rivaroxaban. The outcome was very favorable at 48h. The patient was seen at 4 months and had not had a recurrent episode. DISCUSSION: The diagnosis of DVT of the upper limb is basically clinical. There is a clinical probability score for the introduction of anticoagulation even if the duplex-Doppler fails to visualize DVT, a situation that can occur due to the clavicular superposition in this region. Exercise-induced DVT should be suspected in patients with minimally intense but repeated exercise (hyper-abduction), e.g. as here playing the violin. Anticoagulation is the treatment of choice. The role for surgery and pharmacomechanical strategies remains to be defined. CONCLUSION: Exercise-induced thrombosis (Paget-Schroetter syndrome) should be suspected in young patients free of any comorbidity who develop a thrombosis of the upper limb. Studies comparing different therapeutic options would be useful to achieve more homogeneous management practices despite the heterogeneous clinical presentations.

Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an open-label randomized control trial.

BACKGROUND & AIMS: Eating habits may influence the life span and the quality of ageing process by modulating inflammation. The RISTOMED project was developed to provide a personalized and balanced diet, enriched with or without nutraceutical compounds, to decrease and prevent inflammageing, oxidative stress and gut microbiota alteration in healthy elderly people. This paper focused on the effect on inflammation and metabolism markers after 56 days of RISTOMED diet alone or supplementation with three nutraceutical compounds. METHODS: A cohort of 125 healthy elderly subjects was recruited and randomized into 4 arms (Arm A, RISTOMED diet; Arm B, RISTOMED diet plus VSL#3 probiotic blend; Arm C, RISTOMED diet plus AISA d-Limonene; Arm D, RISTOMED diet plus Argan oil). Inflammatory and metabolism parameters as well as the ratio between Clostridium cluster IV and Bifidobacteria (CL/B) were collected before and after 56 days of dietary intervention, and their evolution compared among the arms. Moreover, participants were subdivided according to their baseline inflammatory parameters (erythrocytes sedimentation rate (ESR), C-Reactive Protein, fibrinogen, Tumor Necrosis Factor-alfa (TNF-α), and Interleukin 6) in two clusters with low or medium-high level of inflammation. The evolution of the measured parameters was then examined separately in each cluster. RESULTS: Overall, RISTOMED diet alone or with each nutraceutical supplementation significantly decreased ESR. RISTOMED diet supplemented with d-Limonene resulted in a decrease in fibrinogen, glucose, insulin levels and HOMA-IR. The most beneficial effects were observed in subjects with a medium-high inflammatory status who received RISTOMED diet with AISA d-Limonene supplementation. Moreover, RISTOMED diet associated with VSL#3 probiotic blend induced a decrease in the CL/B ratio. CONCLUSIONS: Overall, this study emphasizes the beneficial anti-inflammageing effect of RISTOMED diet supplemented with nutraceuticals to control the inflammatory status of elderly individuals.

Alpine Skiing With total knee ArthroPlasty (ASWAP): impact on molecular and architectural features of musculo-skeletal ageing.

This study investigated features of skeletal muscle ageing in elderly individuals having previously undergone unilateral total knee arthroplasty (TKA) and whether markers of sarcopenia could be mitigated by a 12-week alpine skiing intervention. Novel biomarkers agrin, indicative of neuromuscular junction (NMJ) degeneration, tumor suppressor protein p53, associated with muscle atrophy, and a new ultrasound-based muscle architecture biomarker were used to characterize sarcopenia. Participant details and study design are presented by Kösters et al. (2015). The results of this study show that NMJ degeneration is widespread among active septuagenarians previously subjected to TKA: all participants showed elevated agrin levels upon recruitment. At least 50% of individuals were identified as sarcopenic based on their muscle architecture, supporting the hypothesis that NMJ alterations precede sarcopenia. Notably, sarcopenia was strongly associated with the expression of p53, which seems to confirm its validity as a biomarker of muscle atrophy. Training did not significantly modify any of these biomarkers. In view of the lack of accretion of muscle mass in response to the alpine skiing intervention, we hypothesize that local muscle inflammation and oxidative stress may have blunted the anabolic response to training and promoted muscle breakdown in this elderly post-TKA population.

TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells.

Aberrant DNA methylation can lead to genome destabilization and to deregulated gene expression. Recently, 5-hydroxymethylcytosine (5hmC), derived from oxidation of 5-methylcytosine (5mC) by the Ten-Eleven Translocation (TET) enzymes, has been detected. 5hmC is now considered as a new epigenetic DNA modification with relevant roles in cell homeostasis regulating DNA demethylation and transcription. Our aim was to investigate possible changes in the DNA methylation/demethylation machinery in MS. We assessed the expression of enzymes involved in DNA methylation/demethylation in peripheral blood mononuclear cells (PBMCs) from 40 subjects with MS and 40 matched healthy controls. We performed also, DNA methylation analysis of specific promoters and analysis of global levels of 5mC and 5hmC. We show that TET2 and DNMT1 expression is significantly down-regulated in MS PBMCs and it is associated with aberrant methylation of their promoters. Furthermore, 5hmC is decreased in MS PBMCs, probably as a result of the diminished TET2 level.

Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells. The etiology of ALL is believed to be multifactorial and likely to involve an interplay of environmental and genetic variables. We performed a genome-wide association study of 355 750 single-nucleotide polymorphisms (SNPs) in 474 controls and 419 childhood ALL cases characterized by a t(12;21)(p13;q22) - the most common chromosomal translocation observed in childhood ALL - which leads to an ETV6-RUNX1 gene fusion. The eight most strongly associated SNPs were followed-up in 951 ETV6-RUNX1-positive cases and 3061 controls from Germany/Austria and Italy, respectively. We identified a novel, genome-wide significant risk locus at 3q28 (TP63, rs17505102, P(CMH)=8.94 × 10(-9), OR=0.65). The separate analysis of the combined German/Austrian sample only, revealed additional genome-wide significant associations at 11q11 (OR8U8, rs1945213, P=9.14 × 10(-11), OR=0.69) and 8p21.3 (near INTS10, rs920590, P=6.12 × 10(-9), OR=1.36). These associations and another association at 11p11.2 (PTPRJ, rs3942852, P=4.95 × 10(-7), OR=0.72) remained significant in the German/Austrian replication panel after correction for multiple testing. Our findings demonstrate that germline genetic variation can specifically contribute to the risk of ETV6-RUNX1-positive childhood ALL. The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis.

The recurrent cervical swelling syndrome.

The objective of this study is to report an overlooked cause of cervical swelling linked to a thoracic duct (TD) intraluminal obstruction. Four consecutive patients underwent supraclavicular fossa echo-colour-Doppler assessment (ECD) because of recurrent spontaneous cervical swelling. In all patients, during the swelling period we documented a TD dilation with hyperechogenic content, resulting undetectable during asymptomatic periods; ECD also allowed an effective differential diagnosis with TD cysts, obstructive malignancy or other causes of cervical swelling. In conclusion, ECD is to be considered an effective tool in cervical swelling and TD anomalies investigation.

'Immunogenetics of Aging': report on the activities of the 15th International HLA and Immunogenetics Working Group and 15th International HLA and Immunogenetics Workshop.

'Immunogenetics of Aging' is a component that was first included in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th Workshop. The aim of this component was to assess the impact of human leukocyte antigen (HLA) genes, cytokine genes, and some innate immunity genes such as killer-cell immunoglobulin-like receptors (KIRs) and mannose-binding lectin 2 (MBL2) in successful aging and their contribution to the better understanding of immune dysfunction in old age. Within the 15th IHIWS new populations were included in the analysis. Additional cytokine gene polymorphisms were assessed and innate immunity genes were analyzed for possible relevance in longevity. The results showed that longevity might be associated with anti-inflammatory cytokine gene profiles, decreased frequency of interleukin-10 (IL-10) and transforming growth factor-B1 haplotypes associated with a low level of gene expression, and increased frequency of haplotypes determining a high level of expression. Extended tumor necrosis factor-A and IL-12B genotypes were also likely relevant to longevity. Data also showed that innate immunity genes are associated with susceptibility to infections in the elderly and showed that these genes might be an important genetic marker in aging. Decreased frequencies of KIR2DS5 and A1B10 haplotypes, and an increased proportion of MBL2-deficient haplotypes were found in the group with higher cytomegalovirus-specific IgG antibody levels. Together, these studies emphasize the relevance of genes regulating immune functions in maintaining human longevity and stress the importance of further clarifying their impact on successful aging.

Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery.

BACKGROUND: : This study evaluated the incidence of postoperative delirium (POD) in elderly patients undergoing general surgery, the risk factors associated with POD, and its impact on hospital stay and mortality. METHODS: : Patients aged over 65 years who had emergency or elective operations were eligible for this case-control study. Risk factors significantly associated with POD using univariable analysis were entered into multivariable analysis, to establish those independently associated with POD. RESULTS: : A total of 351 patients (357 admissions) were enrolled in the study. The incidence of POD was 13.2 per cent (17.9 per cent for emergency operations). Independent variables associated with POD were: age above 75 years, co-morbidity, preoperative cognitive impairment, psychopathological symptoms and abnormal glycaemic control. Median length of hospital stay was 21 (range 1-75) days for patients with POD versus 8 (range 1-79) days for control patients (P < 0.001). The hospital mortality rate was 19 and 8.4 per cent respectively (P = 0.021). CONCLUSION: : The incidence of POD is high in elderly patients for both emergency and elective surgery, leading to an increase in hospital stay and perioperative mortality. To minimize POD, associated risk factors of co-morbidity, cognitive impairment, psychopathology and abnormal glycaemic control must be identified and treated.

Association of p53 polymorphisms and colorectal cancer: modulation of risk and progression.

OBJECTIVES: p53 Gene variants BstUI RFLP at codon 72 in exon 4, 16bp tandem repeat in intron 3 and MspI RFLP in intron 6, which code for two functionally different protein isoforms, have been shown to modulate susceptibility to different types of human neoplasms. METHODS: p53 genotype was assessed in 90 CRC patients, 321 age-matched controls and 322 centenarians. RESULTS: The p53 codon 72 arginine, the p53 16bp deletion, and the MspI RFLP were significantly more frequent in CRC patients in comparison to the controls and to the centenarians (odd ratio 1.44 and 1.93). In the CRC group, the BstUI RFLP polymorphism was the more frequent combination (62.2%), and it was significantly associated with highly infiltrating (p<0.01), poorly differentiated (p<0.01), and metastatic (p<0.05) tumours. Our findings indicate that the p53 codon 72 polymorphisms are associated with a higher risk of CRC and are associated with more advanced and undifferentiated tumours.

Immunosenescence and immunogenetics of human longevity.

At present, individuals can live up to 80-120 years, a time much longer than that of our ancestors, as a consequence of the improvements in life conditions and medical care. Thus, the human immune system has to cope with a lifelong and evolutionarily unpredicted exposure to a variety of antigens, which are at the basis of profound age-related changes globally indicated as immunosenescence, a multifaceted phenomenon that increases morbidity and mortality due to infections and age-related pathologies. The major changes occurring during immunosenescence are the result of the accumulation of cellular, molecular defects and involutive phenomena (such as thymic involution) occurring concomitantly to a hyperstimulation of both innate and adaptive immunity (accumulation of expanded clones of memory and effector T cells, shrinkage of the T cell receptor repertoire, progressive activation of macrophages), and resulting in a low-grade, chronic state of inflammation defined as inflammaging. It is unknown whether inflammaging, which represents a risk factor for most age-related pathologies, is a cause or rather an effect of the aging process. In this complex scenario, the role of genetic background likely represents a fundamental variable to attain successful aging and longevity. Accordingly, centenarians seem to be equipped with gene variants that allow them to optimize the balance between pro- and anti-inflammatory molecules, and thus to minimize the effects of the lifelong exposure to environmental insults and stressors. The remarkable features of the genetics of aging and longevity are reviewed, stressing the unexpected and unusual results obtained regarding such a postreproductive type of genetics.

The immune system in extreme longevity.

Recent observations indicate that immunosenescence is not accompanied by an unavoidable and progressive deterioration of the immune function, but is rather the result of a remodeling where some functions are reduced, others remain unchanged or even increased. In addition, it appears that the ancestral/innate compartment of the immune system is relatively preserved during aging in comparison to the more recent and sophisticated adaptive compartment that exhibit more profound modifications. The T-cell branch displays an age-dependent decline of the absolute number of total T-cells (CD3+), involving both CD4+ and CD8+ subsets, accompanied by an increase of NK cells with well-preserved cytotoxic function and by a reduction of B-cells. One of the main characteristics of the immune system during aging is a progressive, age-dependent decline of the virgin T-cells (CD95-), which is particularly profound at the level of the CD8+ subpopulation of the oldest old subjects. The progressive exhaustion of this important T-cell subpopulation dedicated primarily to the defense against new antigenic challenges (viral, neoplastic, bacterial ones), could be a consequence of both the thymic involution and the lifelong chronic antigenic stimulation. The immune function of the elderly, is therefore weakened by the exhaustion of CD95- virgin cells that are replaced by large clonal expansions of CD28- T-cells. The origin of CD28- cells has not been completely clarified yet, but it is assumed that they represent cells in the phase of replicative senescence characterized by shortening telomers and reduced proliferative capacity. A major characteristic of the immune system during aging is the up-regulation of the inflammatory responses which appears to be detrimental for longevity. In this regard, we have recently observed a progressive age-dependent increase of type 1(IL-2, IFN-gamma, TNF-alpha) and type 2 (IL-4, IL-6, IL-10) positive CD8+ T-cells; in particular, type 1 cytokine-positive cells significantly increased, with age, in all CD8+ subsets particularly among effector/cytotoxic and memory cells. A major force able to drive a chronic pro-inflammatory state during aging may be represented by persistent viral infections by EBV and CMV. Therefore, we have determined the frequency and the absolute number of viral antigen-specific CD8+ T-cells in subjects older than 85 years, who were serologically positive for CMV or EBV. In the majority of these subjects we detected the presence of T lymphocytes positive for epitopes of CMV or EBV. In all subjects the absolute number of CMV-positive CD8+ cells outnumbered that of EBV-positive ones. In addition, the majority of CMV+ T cells were included within the CD28- subpopulation, while EBV+ T cells belonged mainly to the CD28+ subset. These data indicate that the chronic antigenic stimulation induced by persistent viral infections during aging bring about important modifications among CD8+ subsets, which are particularly evident in the presence of CMV persistence. The age-dependent expansions of CD8+CD28- T-cells, mostly positive for pro-inflammatory cytokines and including the majority of CMV-epitope-specific cells, underlines the importance of chronic antigenic stimulation in the pathogenesis of the main immunological alterations of aging and may favour the appearance of several pathologies (arteriosclerosis, dementia, osteoporosis, cancer) all of which share an inflammatory pathogenesis.

Curcumin in cell death processes: a challenge for CAM of age-related pathologies.

Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.

Different antioxidant profiles in Italian centenarians: the Sardinian peculiarity.

In this study, 153 Italian centenarians from four different geographical areas, including Modena (northern Italy), Ancona (central Italy), Perugia (central Italy) and Sardinia island (AKEA Project) were enrolled. Plasma levels of vitamin C, uric acid, vitamin A and vitamin E as well as the activities of superoxide dismutase and glutathione peroxidase were measured. Subjects were compared to a younger control population of the same areas, divided into three age groups:

Effect of etanercept on insulin sensitivity in nine patients with psoriasis.

Metabolic syndrome is associated to chronic low grade inflammation, characterized by increased levels of inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-6 (IL-6). In particular, TNF-alpha causes a decrease in the insulin-stimulated kinases related to the early phases of the insulin cascade, thereby leading to insulin resistance. Etanercept is a human fusion protein used in the treatment of psoriasis and inflammatory arthritis. It blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. The aim of this case report study is to verify the effect of Etanercept on insulin sensitivity, lipid profile and inflammatory status in psoriatic patients. Nine psoriatic patients with stable, active, plaque type psoriasis were enrolled and treated with Etanercept for 24 weeks. We found an improvement in the metabolic assessment with a significant reduction of insulin plasma levels. In particular, this treatment allows to maintain their euglycemic state with lower insulin plasma levels, as confirmed by the improved Homeostasis Model Assessment (HOMA) index. We conclude that Etanercept, probably acting on inflammation, improves insulin sensitivity in psoriatic subjects.

Genes, ageing and longevity in humans: problems, advantages and perspectives.

Many epidemiological data indicate the presence of a strong familial component of longevity that is largely determined by genetics, and a number of possible associations between longevity and allelic variants of genes have been described. A breakthrough strategy to get insight into the genetics of longevity is the study of centenarians, the best example of successful ageing. We review the main results regarding nuclear genes as well as the mitochondrial genome, focusing on the investigations performed on Italian centenarians, compared to those from other countries. These studies produced interesting results on many putative "longevity genes". Nevertheless, many discrepancies are reported, likely due to the population-specific interactions between gene pools and environment. New approaches, including large-scale studies using high-throughput techniques, are urgently needed to overcome the limits of traditional association studies performed on a limited number of polymorphisms in order to make substantial progress to disentangle the genetics of a trait as complex as human longevity.