Enhanced peripheral levels of BDNF and proBDNF: elucidating neurotrophin dynamics in cocaine use disorder.

Brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF, are known to significantly contribute to brain homeostasis, neuroplasticity, and neuronal remodeling. Although these neurotrophins are thought to have opposing roles, both play a critical part in shaping long-lasting behavioral changes following substance use. In this context, our study sought to explore the implications of these neurotrophins in the pathophysiology of cocaine use disorder (CUD). We conducted a case-control study, which included 28 individuals seeking treatment for CUD and 38 matched healthy participants. We measured peripheral neurotrophin concentrations via an enzyme-linked immunosorbent assay. Additionally, all participants were screened for cocaine-associated pathways (e.g., cocaine intake, craving intensity), along with associated psychopathological data. Our findings highlighted an increased concentration of BDNF and proBDNF in CUD individuals when compared to healthy controls (BDNF: 18092.80 ± 6844.62 vs. 11334.42 ± 5061.85 pg/ml, p < 0.001; proBDNF: 87.03 ± 33.23 vs. 55.70 ± 23.26 ng/ml, p < 0.001). We further corroborated the relationship between neurotrophin levels and CUD using a linear regression model. Nevertheless, there was no significant difference in the proBDNF to BDNF ratio between the two groups. Interestingly, our study also demonstrated the influence of factors like usage of psychotropic medications, history of psychiatric hospitalizations, and psychiatric diagnoses on neurotrophin dynamics. In conclusion, our study underscores the significance of neurotrophin fluctuations in CUD. The observed increase in BDNF and proBDNF levels could play a pivotal role in driving craving and relapse risk. Thus, a nuanced understanding of these neurobiological underpinnings in CUD might contribute to the development of more targeted and effective therapeutic strategies.

Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia.

OBJECTIVES: Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. METHODS: We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. RESULTS: S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 µg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. CONCLUSIONS: The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE.

Intraoperative Iridectomy in Femto-Laser Assisted Smaller-Incision New Generation Implantable Miniature Telescope.

BACKGROUND: In this study, we aimed to report the short-term (6 months) effects on visual functionality and safety of femto-laser assisted smaller-incision new-generation implantable miniature telescope (SING-IMT™) implanting, particularly related to postsurgical intraocular pressure increase, in patients suffering from end-stage age-related macular degeneration (AMD) and cataract. This device, designed for monocular use, aims to minimise the impact of the central scotoma by projecting the images onto a larger area of the photoreceptors surrounding the macula. METHODS: In this prospective multicentric observational case series study, 6 eyes of 6 patients who underwent SING-IMT™ implantations were enrolled. At baseline and 6 months follow-up, best corrected distance visual acuity (BCDV) and best corrected near visual acuity (BCNVA), intraocular pressure (IOP), anterior chamber depth, endothelial cells count were assessed. In addition, IOP was also measured at 7, 15, 30, 45 days, and at 3 months follow-up. Finally, the incidence of complications was evaluated. RESULTS: At final follow-up, in the study eyes, mean BCDVA improved by +10.0 letters (6.25; 13.8) letters and mean BCNVA improved by -0.30 logMAR (-0.55; -0.20). At postoperative month 6, we reported a mean IOP decrease of 4.50 mmHg (-5.75; -0.25). Interestingly, 83.3% of patients had an increased IOP value in at least one of the first two postoperative follow-ups (7 days and 15 days). In patients in whom intraoperative mechanical iridotomy was not performed, it was necessary to perform a postoperative YAG laser iridotomy to improve IOP management. Compared to the baseline, ECD loss at 6 months follow-up was 12.6%. CONCLUSIONS: The SING IMT™ device was found to be effective in the distance and near vision improvement, without serious postoperative complications. We recommend intraoperative mechanical iridectomy in order to easily manage post-operative IOP and to avoid sudden IOP rise with its possible consequences. These good results can be a hope to partially improve the quality of life of patients suffering from severe end stage macular atrophy.

Impact of sleep disorders and disease duration on neurotrophins levels in cocaine use disorder.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) and its precursor proBDNF contribute to brain plasticity and neuronal remodeling. Recently, the ratio between proBDNF and BDNF (RpB) has been proposed as a possible marker in major psychiatric disorders. Convergent lines of evidence suggest neurotrophins alterations could be involved into the pathophysiology of Cocaine Use Disorder (CUD) and insomnia. The aims of the present study are to evaluate the correlations between neurotrophins levels, insomnia and clinical features among CUD patients. MATERIALS AND METHODS: Subjects with a moderate to severe CUD were recruited. ProBDNF, BDNF and consequently RpB values were analyzed using ELISA technique. Insomnia severity index (ISI) scale was used to assess the severity of insomnia. Sociodemographic characteristics and CUD habits (e.g., years of cocaine use) were also collected. RESULTS: Twenty-four subjects (mean age 39.3 ± 6.7 years) were recruited. Correlation analysis showed that lower values of RpB were associated with higher ISI score (r = -0.469; p = 0.021), longer history of cocaine use (r = -0.584, p = 0.022) and higher amount of cocaine used (r = -0.655, p = 0.004). DISCUSSION: These preliminary findings may offer a novel insight on neurobiological alterations sustaining cocaine use. Lower RpB, as observed both in high insomnia levels and in chronic cocaine use, could induce a neuroprotective state as a synaptic homeostatic response to chronic damage. These findings also highlight the important role of neurotrophins balance on neurobiological alterations induced by cocaine misuse and insomnia, suggesting that RpB could be considered as a marker of neurotrophic and metabolic state of neural tissue.

Swept Source Optical Coherence Tomography Assessment of Bursa Premacularis in Healthy Eyes.

PURPOSE: To describe the reliability and the limits of bursa premacularis (BPM) evaluation using a swept source optical coherence tomography (SS-OCT) device with enface and 16 mm-high definition (HD) longitudinal scans. METHODS: 60 eyes of 60 subjects were enrolled and imaged with SS-OCT system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). BPM area was measured using enface scans imported to ImageJ. HD horizontal and vertical longitudinal scans centered at the fovea were used to detect width (W) and central thickness (CT) of BPM at baseline (T0) and after 30 minutes (T30) performed by two different observers. An enhanced vitreous visualization software provided by the manufacturer of the device was used to highlight vitreous structures. RESULTS: BPM was identifiable in 100% of eyes using both horizontal and vertical longitudinal scans. On horizontal scan, BPM was not entirely measurable in 21.7% and in 18.3% of cases at T0 and T30, respectively. On vertical scan, BPM was not entirely measurable in 75.0% and in 81.7% at T0 and T30, respectively. No statistically significant differences were found between the two different time measurements with an intraclass correlation coefficient above 70%. Median BPM area was 26.9 (Q1-Q3: 19.5-40.5) mm2. In en face imaging, the most frequent BPM shape was the boat one. CONCLUSION: SS-OCT is a reliable tool for a detailed quantification and mapping of BPM, and it is able to add useful details about the morphological BPM features in youth population. However, the enhanced visualization of the vitreous structures is still a challenge, also with the most forefront devices.

HLA-G14bp ins/del polymorphism and post-transplant weight gain in kidney transplantation: potential implications beyond tolerance.

BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical HLA molecule with immunomodulant and immunosuppressive functions, involved in transplantation tolerance. HLA-G14bp ins/del polymorphism in exon 8 has been associated with allograft rejection and kidney transplant outcome, with controversial results. We investigated associations of HLA-G14bp ins/del polymorphism on onset of some of the main post-transplant risk factors, like excess body weight, lipid abnormalities, increased fasting plasma glucose. Polymorphisms of cytokines with both immunosuppressive and metabolic effects were also assessed for comparisons and associated analysis. METHODS: The present study involved kidney transplant recipients (n = 173) in which body mass index, cholesterol, triglycerides, fasting plasma glucose were registered in the first years after transplantation and analyzed in association with genotypes. Presence of hypertension and smoking habits, demographic, transplant-related and therapeutic data of patients were also recorded. Polymerase chain reaction, sequence-specific primer amplification and Taqman allelic discrimination techniques were used for genotyping of HLA-G14bp ins/del, interleukin (IL)-10(-1082G > A,-819 T > C,-592A > C), transforming growth factor-ß(+ 869 T > C,+915C > G), IL-6(-174G > C), tumor necrosis factor-α(-308G > A) and IL-18(-137G > C,-607C > A). Effects of genotypes on clinical markers at each time point (pre-transplant and 1 to 5 years after transplant) were analyzed using a repeated-measures general linear model analysis; adjustment for potential confounders was performed. RESULTS: Results showed that HLA-G14bp ins/ins was significantly associated with obesity, in particular after transplantation (3 years, p = 0.002, OR = 4.48, 95% CI:1.76-11.41). Post-transplant body mass index was significantly increased in HLA-G14bp ins/ins carriers (3 and 4 years, p = 0.033 and p = 0.044); effects of HLA-G14bp genotypes on post-transplant BMI were confirmed by using repeated-measures analysis and after controlling for confounding variables. Cytokine genotypes did not associate with the examined factors. CONCLUSIONS: The study of transplanted patients allowed to evidence a potential relationship between post-transplant weight gain and HLA-G14bp ins/del polymorphism, previously involved in rejection for its immunosuppressive/tolerogenic activity. This novel association could widen the knowledge of the role and functions of HLA-G molecules in diseases and transplantation.

Infected Nonhealing Wound in a Kidney Transplant Recipient: Successful Treatment With Topical Homologous Platelet-Rich Gel.

Impaired would healing is a known adverse effect of chronic immunosuppression. Solid-organ transplant recipients undergoing major abdominal surgery have an increased risk of wound-related complications compared with the general population. In this subset of patients, surgical site infections and wound dehiscence must be aggressively treated to avoid sepsis, graft loss, and death. Recently, topical application of platelet-rich plasma has been proposed as an alternative therapeutic option to enhance wound healing in difficult cases. Unfortunately, randomized controlled trials evaluating the efficacy of platelet-rich plasma compared with standard or advanced wound management are lacking, and the literature mostly refers to anecdotal reports in patients with no evidence of wound infection. This report documents a kidney transplant recipient who experienced spontaneous bladder rupture because of gangrenous cystitis. After an exploratory laparotomy and bladder repair, the patient developed a deep surgical site infection by multidrug resistant Acinetobacter baumannii and extensive wound dehiscence. Advanced wound management and vacuum-assisted closure therapy were ineffective. Topical homologous platelet-rich gel was used resulting in significant wound healing, without infections or immunologic complications.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Coupled Plasma Filtration Adsorption in Patients with a History of Kidney Transplantation: Report of Two Cases.

Coupled plasma filtration adsorption (CPFA) is an extracorporeal treatment based on plasma filtration associated with an adsorbent cartridge and hemofiltration. CPFA is able to remove inflammatory mediators and it has been used to treat severe sepsis, septic shock and multiple organ dysfunction syndrome. Limited experience exists on the use of CPFA after solid organ transplantation. We report our experience with CPFA in 2 kidney transplant recipients with post-nephrolithotomy septic shock and severe unexplained rhabdomyolysis. In both the cases, excellent results were observed. In selected cases, CPFA can be safely and effectively used in patients with a solid organ transplant. However, additional studies are needed in this particular setting, to further investigate the potential role of CPFA for the treatment of other conditions associated with excessive inflammation, such as in rheumatologic disorders and delayed graft function.

One-shot versus multidose perioperative antibiotic prophylaxis after kidney transplantation: a randomized, controlled clinical trial.

BACKGROUND: There is no consensus on the optimal perioperative antibiotic prophylaxis regimen for renal transplant recipients. Some studies have reported that irrigation of the wound at the time of closure without systemic antibiotics may suffice to minimize the risk for surgical site infection (SSI), but many centers still use long-term, multidose regimens in which antibiotics are administered until removal of foreign bodies occur, such as the urethral catheter, drain and central line. METHODS: We designed a prospective, randomized, multicenter, controlled trial to compare a single dose versus a multidose regimen of systemic antibiotic prophylaxis in adult, nondiabetic, non-morbidly obese patients undergoing renal transplantation. The primary endpoint was the incidence of SSI; the assessment of other infection in the first postoperative month was the secondary endpoint. RESULTS: Two hundred five patients were enrolled and randomized to receive either a single (n = 103) or multidose antibiotic regimen (n = 102) for prophylaxis. The incidences of SSI and urinary tract infection were similar in both groups. CONCLUSION: As the dramatic increase in antibiotic resistance has mandated the implementation of global programs to optimize the use of antibiotic agents in humans, we believe that the single dose regimen is preferred, at least in nondiabetic, non-morbidly obese, adult renal transplant recipients.