Preoperative infection risk assessment in hip arthroplasty a matched-pair study of the reliability of 3 validated risk scales.

Peri-prosthetic infection (PJI) represents one of the most devastating complications of total hip arthroplasty (THA). The aim of this study is to assess the reliability of different PJI risk assessment scales between two matched pairs of THA groups. This study included 37 patients with PJI following THA performed between 2012 and 2020 (Group A). Each patient in this group was matched, based on sex, age, and follow-up duration, with a control patient who underwent the same surgical procedure without any septic complications (Group B) during the same period. Each patient's assessment included the American Society of Anesthesiologists (ASA) score and a retrospective evaluation using three different preoperative, specific PJI risk assessment scales: the International Consensus Meeting (ICM) Preoperative Risk Calculator for PJI, the Mayo PJI Risk Score, and the KLIC-score. The two groups were statistically compared using descriptive analyses, both for binomial data and numerical variables. Statistically significant higher values were observed in the preoperative ASA score and surgical time in Group A. Statistically different higher scores were determined only with the ICM risk calculator score in Group A. No significant differences were found using the KLIC score and Mayo score between the two groups. We emphasize the reliability of the ASA score as a nonspecific preoperative assessment scale for PJI. The ICM risk calculator was confirmed as a reliable, specific preoperative assessment scale for PJI, suggesting its routine adoption in THA clinical practice.

The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study.

The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.

Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis.

RATIONALE: Stress is a risk factor for psychosis and treatments which mitigate its harmful effects are needed. Cannabidiol (CBD) has antipsychotic and anxiolytic effects. OBJECTIVES: We investigated whether CBD would normalise the neuroendocrine and anxiety responses to stress in clinical high risk for psychosis (CHR) patients. METHODS: Thirty-two CHR patients and 26 healthy controls (HC) took part in the Trier Social Stress Test (TSST) and their serum cortisol, anxiety and stress associated with public speaking were estimated. Half of the CHR participants were on 600 mg/day of CBD (CHR-CBD) and half were on placebo (CHR-P) for 1 week. RESULTS: One-way analysis of variance (ANOVA) revealed a significant effect of group (HC, CHR-P, CHR-CBD (p = .005) on cortisol reactivity as well as a significant (p = .003) linear decrease. The change in cortisol associated with experimental stress exposure was greatest in HC controls and least in CHR-P patients, with CHR-CBD patients exhibiting an intermediate response. Planned contrasts revealed that the cortisol reactivity was significantly different in HC compared with CHR-P (p = .003), and in HC compared with CHR-CBD (p = .014), but was not different between CHR-P and CHR-CBD (p = .70). Across the participant groups (CHR-P, CHR-CBD and HC), changes in anxiety and experience of public speaking stress (all p's < .02) were greatest in the CHR-P and least in the HC, with CHR-CBD participants demonstrating an intermediate level of change. CONCLUSIONS: Our findings show that it is worthwhile to design further well powered studies which investigate whether CBD may be used to affect cortisol response in clinical high risk for psychosis patients and any effect this may have on symptoms.

Childhood trauma and being at-risk for psychosis are associated with higher peripheral endocannabinoids.

BACKGROUND: Evidence has been accumulating regarding alterations in components of the endocannabinoid system in patients with psychosis. Of all the putative risk factors associated with psychosis, being at clinical high-risk for psychosis (CHR) has the strongest association with the onset of psychosis, and exposure to childhood trauma has been linked to an increased risk of development of psychotic disorder. We aimed to investigate whether being at-risk for psychosis and exposure to childhood trauma were associated with altered endocannabinoid levels. METHOD: We compared 33 CHR participants with 58 healthy controls (HC) and collected information about previous exposure to childhood trauma as well as plasma samples to analyse endocannabinoid levels. RESULTS: Individuals with both CHR and experience of childhood trauma had higher N-palmitoylethanolamine (p < 0.001) and anandamide (p < 0.001) levels in peripheral blood compared to HC and those with no childhood trauma. There was also a significant correlation between N-palmitoylethanolamine levels and symptoms as well as childhood trauma. CONCLUSIONS: Our results suggest an association between CHR and/or childhood maltreatment and elevated endocannabinoid levels in peripheral blood, with a greater alteration in those with both CHR status and history of childhood maltreatment compared to those with either of those risks alone. Furthermore, endocannabinoid levels increased linearly with the number of risk factors and elevated endocannabinoid levels correlated with the severity of CHR symptoms and extent of childhood maltreatment. Further studies in larger cohorts, employing longitudinal designs are needed to confirm these findings and delineate the precise role of endocannabinoid alterations in the pathophysiology of psychosis.

Associations between psychosis endophenotypes across brain functional, structural, and cognitive domains.

BACKGROUND: A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related. METHODS: This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes. RESULTS: The P300 amplitude and latency were not associated (regression coef. -0.06, 95% CI -0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10-0.28, p 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships. CONCLUSIONS: The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.

Cell-mediated immune response in psoriasis and psoriatic arthritis.

It has been previously described an impairment of cell-mediated immune response in psoriasis. In the present paper we have evaluated lymphocyte surface markers, non specific immunity, lymphokine secretion and antibody synthesis in a group of patients with psoriasis (PS) and with anti-inflammatory drug treated or gold-treated psoriatic arthritis (PsA). No significant differences are found in terms of T lymphocyte subpopulation frequency, even if a lower CD8+/CD4+ ratio was observed in all patients. In spite of an increased percentage of B lymphocytes, B cell polyclonal response is significantly decreased in the presence of either T cell-independent or T cell-dependent polyclonal activator. Further studies provide additional supports to these findings, since all psoriatic patients exhibit a deficit of T helper function in an antibody-specific induction system. Gold therapy in PsA led to a partial recovery of T helper function, without affecting the immunoglobulin reduced synthesis. With particular reference to non-specific activities mediated by monocytes and polymorphs (PMN), PMN chemotaxis, phagocytosis and killing and monocyte-mediated phagocytosis are reduced, except for monocyte phagocytosis in anti-inflammatory treated PsA or PMN chemotaxis in gold-treated PsA. Finally, lymphokine release is significantly decreased in all patients. In conclusion, our data provide further evidence for the impairment of immune response in psoriasis and PsA, which may in turn play a key role in the pathogenesis of psoriasis.

Imbalance of T cell immunoregulatory subsets in primary IgA nephropathy.

The peripheral blood distribution of T cell subsets was evaluated in a group of patients with primary IgA nephropathy (IgAN). Results showed that the frequency of helper (CD4+) and suppressor (CD8+) T lymphocytes in IgAN overlapped that seen in healthy blood donors. In addition, the helper T cell subset (CD4+ CDW29+ and CD4+ CD45R+ cells, respectively) proportion was normal, while with particular reference to suppressor T cell subpopulations, a significant decrease of CD8+ CD11+ lymphocytes (the true suppressor cells) was observed in IgAN. These data were further confirmed by the demonstration that monocyte chemotactic responsiveness triggered by lymphocyte-derived chemotactic factor (LDCF), a lymphokine released by CD8+ CD11- cells, was higher in IgAN than in controls. These data suggest that the low frequency of CD8+ CD11+ cells may be responsible for the impaired T cell immunoregulatory activity in patients with IgAN.

Monocyte- and cytokine-mediated effects on T immunoregulatory activity in the elderly.

Aged individuals exhibit an impairment of T helper and/or T suppressor activity on B cell function in an antibody-specific induction system. Further evidence is now provided that soluble suppressive factors acting on monocytes play a key role in such deficits. In fact, overnight preincubation of isolated monocytes and supplementation of autologous lymphocytes reverses the immunoregulatory imbalance. The suppressive factors are also responsible for a decreased interleukin 2 (IL-2) synthesis since a similar pretreatment of cell suspensions or exogenous human IL-1 and/or IL-2 supplementation of aged cell cultures leads to a recovery of T regulatory effects on B cell differentiation. Similar effects are observed in the presence of thymopentin, a well known IL-2 inducer. Interferon alpha and gamma addition to cultures gives rise to a restoration of T immunoregulatory effects. These findings suggest that several mechanisms are involved in the depressed T immunoregulatory activity in the elderly.