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Summary: The seroprevalence of Human herpesvirus-8 (HHV-8) was studied in 56 children aged two to 14 years. Subjects were children seen consecutively in the Children Emergency Room of the University of Calabar Teaching Hospital in January 2000. Sera from the children were screened for antibodies to the small capsid related protein encoded by ORF 65 (Lytic antigen) by the ELISA technique and Latency Associated Nuclear Antigen (LANA) by the immunoflourescent assay. Of the 56 children, 42 (76.9 per cent) had antibodies to at least, one of the antigens. The rate of infection correlated positively with age (r= 0.45; p

Recurrence of meningiomas after surgery and radiotherapy deserves specific attention because of the lack of active third-line therapies. Somatostatin receptors are usually overexpressed on the cell membrane of meningiomas, and this has led the way to a radionuclide theranostic approach. Diagnoses with 68 Ga-DOTA-octreotide and peptide receptor radionuclide therapy (PRRT) with 90 Y/ 177 Lu-DOTA-octreotide are currently possible options within experimental protocols or as compassionate use in small patient groups. Methods: From October 2009 to October 2021, 42 meningioma patients with radiologic recurrence after standard therapies were treated with 90 Y-DOTATOC (dosage of 1.1 or 5.5 GBq) or with 177 Lu-DOTATATE (dosage of 3.7 or 5.5 GBq) in a mean of 4 cycles. All patients showed intense uptake at diagnostic 68 Ga-DOTATOC PET/CT or in an 111 In-octreotide scan. Results: Of 42 patients treated, 5 patients received 90 Y-DOTATOC with a cumulative activity of 11.1 GBq and 37 patients received 177 Lu-DOTATATE with a cumulative activity of 22 GBq. The disease control rate was 57%. With a median follow-up of 63 mo, median progression-free survival was 16 mo, and median overall survival was 36 mo. Retreatment 177 Lu-PRRT was performed in 6 patients with an administered median activity of 13 GBq in a mean of 5 cycles. With a 75.8-mo follow-up, median progression-free survival and overall survival were 6.5 and 17 mo, respectively. Only 1 patient discontinued the treatment because of grade 3 platelet toxicity. A rapidly transient grade 2 neutropenia was recorded in 1 retreated patient. Conclusion: PRRT in patients with advanced meningiomas overexpressing somatostatin receptor 2 was active and well tolerated, showing a 57% disease control rate. Furthermore, PRRT could represent a potential retreatment option. Further studies, also in combination with other treatments, are warranted., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.

Aims: The primary aim of this study was to assess whether non-fatal postoperative venous thromboembolism (VTE) within six months of surgery influences the knee-specific functional outcome (Oxford Knee Score (OKS)) one year after total knee arthroplasty (TKA). Secondary aims were to assess whether non-fatal postoperative VTE influences generic health and patient satisfaction at this time., Methods: A study of 2,393 TKAs was performed in 2,393 patients. Patient demographics, comorbidities, OKS, EuroQol five-dimension score (EQ-5D), and Forgotten Joint Score (FJS) were collected preoperatively and one year postoperatively. Overall patient satisfaction with their TKA was assessed at one year. Patients with VTE within six months of surgery were identified retrospectively and compared with those without., Results: A total of 37 patients (1.5%) suffered a VTE and were significantly more likely to have associated comorbidities of stroke (p = 0.026), vascular disease (p = 0.026), and kidney disease (p = 0.026), but less likely to have diabetes (p = 0.046). In an unadjusted analysis, patients suffering a VTE had a significantly worse postoperative OKS (difference in mean (DIM) 4.8 (95% confidence interval (CI) 1.6 to 8.0); p = 0.004) and EQ-5D (DIM 0.146 (95% CI 0.059 to 0.233); p = 0.001) compared with patients without a VTE. After adjusting for confounding variables VTE remained a significant independent predictor associated with a worse postoperative OKS (DIM -5.4 (95% CI -8.4 to -2.4); p < 0.001), and EQ-5D score (DIM-0.169 (95% CI -0.251 to -0.087); p < 0.001). VTE was not independently associated with overall satisfaction after TKA (odds ratio 0.89 (95% CI 0.35 to 2.07); p = 0.717)., Conclusion: Patients who had a VTE within six months of their TKA had clinically significantly worse knee-specific outcome (OKS) and general health (EQ-5D) scores one year postoperatively, but the overall satisfaction with their TKA was similar to those patients who did not have a VTE. Cite this article: Bone Joint J  2021;103-B(7):1254-1260.

Background: Therapeutic cooling initiated during cardiopulmonary resuscitation (intra arrest therapeutic hypothermia, IATH) provided diverging effect on neurological outcome of out-of-hospital cardiac arrest (OHCA) patients depending on the initial cardiac rhythm and the cooling methods used., Methods: We performed a systematic search of PubMed, EMBASE and the CENTRAL databases using established Medical Subject Headings (MeSH) terms for IATH and OHCA. Only studies comparing IATH to standard in-hospital targeted temperature management (TTM) were selected. We used the revised Cochrane RoB-2 and the Newcastle-Ottawa scale tool to assess risk of bias of each study. Primary outcome was favorable neurological outcome (FO); secondary outcomes included return of spontaneous circulation (ROSC) rate and survival to hospital discharge., Results: Out of 20,950 studies, 8 studies (n = 3493 patients, including 4 randomized trials, RCTs) were included in the final analysis. Compared to controls, the use of IATH was not associated with improved FO (OR 0.96 [95% CIs 0.68-1.37]; p = 0.84), increased ROSC rate (OR 1.11 [95% CIs 0.83-1.49]; p = 0.46) or survival (OR 0.91 [95% CIs 0.73-1.14]; p = 0.43). Significant heterogeneity among studies was observed for the analysis of ROSC rate (I 2  = 69%). Trans-nasal evaporative cooling and cold fluids were explored in two RCTs each and no differences were observed on FO, event when only patients with an initial shockable rhythm were analyzed (OR 1.62 [95% CI 1.00-2.64]; p = 0.05]., Conclusions: In this meta-analysis, IATH was not associated with improved neurological outcome when compared to standard in-hospital TTM, based on very low certainty of evidence., Clinical Trial Registration: PROSPERO (CRD42019130322)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Total hip arthroplasty (THA) is an effective procedure for relieving pain and restoring function in osteoarthritis. A significant proportion of patients have severe disease bilaterally. Consensus regarding safety and selection of patients for simultaneous bilateral THA or the optimal timing for staged THA has not been reached. The aim of this study is to compare rates, causes of revision, and 30-day mortality between simultaneous and staged bilateral THA using data from the Australian Orthopedic National Joint Replacement Registry., Methods: Data for 12,359 bilateral THA procedures were collected from September, 1999 to December, 2017. Rates and causes of revision and 30-day mortality were obtained for simultaneous bilateral and staged procedures with intervals of 1 day-6 weeks, 6 weeks-3 months, and 3 months-6 months. Yearly cumulative percent revision or cumulative percent survival with 95% confidence intervals calculated by the Kaplan-Meier method, and adjusted hazard ratios were used for comparisons., Results: Thirty-day mortality is lower in patients who have bilateral procedures within 6 months, regardless of timing, than those who have unilateral procedures (0.06% vs 0.18%). Staged bilateral THA had a significantly lower mortality than simultaneous bilateral THA (odds ratio 0.175, 95% confidence interval = 0.04-0.78, P = .022). When separate time intervals were compared, no significant differences were seen. Bilateral 6 week-3 months has a higher rate of revision from 1.5 years-2years compared with same day bilaterals (hazard ratio = 2.39, 95% confidence interval = 1.12, 5.09, P = .024). There were no other significant differences in the rate of revision between groups. The most common reasons for revision were fracture, loosening, and infection. Simultaneous bilateral procedures have a significantly higher rate of revision for fracture compared with staging 3-6 months (hazard ratio = 1.96 [1.27, 3.03], P = .002)., Conclusion: This study demonstrates that bilateral THA has a low mortality rate regardless of time interval between procedures. Simultaneous and staged bilateral THA have similar rates of revision., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy., Methods: Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM., Results: Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM- cases. BoM+ had lower overall response rate (ORR; Cohort A: 12% versus 23%, p <  0.0001; Cohort B: 13% versus 22%, p = 0.04), shorter progression free survival (PFS; Cohort A: 3.0 versus 4.0 months, p <  0.0001; Cohort B: 2.7 versus 5.2 months, p <  0.0001) and overall survival (OS; Cohort A: 7.4 versus 15.3 months, p <  0.0001; Cohort B: 5.0 versus 10.9 months, p < 0.0001). Moreover, BoM negatively affected outcome irrespective of performance status (PS; OS in both cohorts: p < 0.0001) and liver metastases (OS cohort A: p < 0.0001; OS Cohort B: p = 0.48). At multivariate analysis, BoM independently associated with higher risk of death (cohort A: HR 1.50; cohort B: HR 1.78)., Conclusions: BoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.

The local mechanical environment at a fracture is known to influence biological factors such as callus formation, immune cell recruitment and susceptibility to infection. Infection models incorporating a fracture are therefore required to evaluate prevention and treatment of infection after osteosynthesis. The aim of this study was to create humane, standardised and repeatable preclinical models of implant-related bone infection after osteosynthesis in the rabbit humerus. Custom-designed interlocked intramedullary nails and commercially available locking plates were subjected to biomechanical evaluation in cadaveric rabbit humeri; a 10-week in vivo healing study; a dose response study with Staphylococcus aureus over 4 weeks; and finally, a long-term infection of 10 weeks in the plate model.Outcome measures included biomechanical testing, radiography, histology, haematology and quantitative bacteriology. Both implants offered similar biomechanical stability in cadaveric bones, and when applied in the in vivo study, resulted in complete radiographic and histological healing and osteotomy closure within 10-weeks. As expected in the infection study, higher bacterial doses led to an increasing infection rate. In both infected groups, there was a complete lack of osteotomy closure at 4 weeks. C-reactive protein (CRP), lymphocyte: granulocyte ratio and weight loss were increased in infected animals receiving IM nails in comparison with non-inoculated equivalents, although this was less evident in the plate group. In the 10-week infection group, healing does not occur in the plated rabbits. We have successfully developed a rabbit model that is suitable for further studies, particularly those looking into preventative strategies for post-traumatic implant-related osteomyelitis.

The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4(+) T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor α (IL-2Rα, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma.