Background: Our aim was to estimate the rates of not achieving a robust/above-average humoral response to the COVID-19 mRNA vaccine in people living with HIV (PLWH) who received ≥2 doses and to ...investigate the role of the CD4 and CD4/CD8 ratio in predicting the humoral response. Methods: We evaluated the humoral anti-SARS-CoV-2 response 1-month after the second and third doses of COVID-19 mRNA vaccine as a proportion of not achieving a robust/above-average response using two criteria: (i) a humoral threshold identified as a correlate of protection against SARS-CoV-2 (<90% vaccine efficacy): anti-RBD < 775 BAU/mL or anti-S < 298 BAU/mL, (ii) threshold of binding antibodies equivalent to average neutralization activity from the levels of binding (nAb titer < 1:40): anti-RBD < 870 BAU/mL or anti-S < 1591 BAU/mL. PLWH were stratified according to the CD4 count and CD4/CD8 ratio at first dose. Logistic regression was used to compare the probability of not achieving robust/above-average responses. A mixed linear model was used to estimate the mean anti-RBD titer at various time points across the exposure groups. Results: a total of 1176 PLWH were included. The proportions of participants failing to achieve a robust/above-average response were significantly higher in participants with a lower CD4 and CD4/CD8 ratio, specifically, a clearer gradient was observed for the CD4 count. The CD4 count was a better predictor of the humoral response of the primary cycle than ratio. The third dose was pivotal in achieving a robust/above-average humoral response, at least for PLWH with CD4 > 200 cells/mm3 and a ratio > 0.6. Conclusions: A robust humoral response after a booster dose has not been reached by 50% of PLWH with CD4 < 200 cells mm3. In the absence of a validated correlate of protections in the Omicron era, the CD4 count remains the most solid marker to guide vaccination campaigns in PLWH.
Summary
Outcomes after transplantation of lungs (LuTX) treated with ex‐vivo lung perfusion (EVLP) are debated. In a single‐center 8 years of retrospective analysis, we compared: donors’ and ...recipients’ characteristics, gas exchange and lung mechanics at ICU admission, 3, 6, and 12 months, and patients’ survival of LuTX from standard donors compared with EVLP‐treated grafts. A total of 193 LuTX were performed. Thirty‐one LuTX, out of 50 EVLP procedures, were carried out: 7 from nonheart beating and 24 from extended criteria brain‐dead donors. Recipients’ characteristics were similar. At ICU admission, compared with standard donors, EVLP patients had worse PaO2/FiO2 276 (206; 374) vs. 204 (133; 245) mmHg, P < 0.05, more frequent extracorporeal support (18% vs. 32%, P = 0.053) and longer mechanical ventilation duration 28 days of ventilator‐free days: 27 (24; 28) vs. 26 (19; 27), P < 0.05. ICU length of stay 4 (2; 9) vs. 6 (3; 12) days, P = 0.208, 28‐day survival (99% vs. 97%, P = 0.735), and 1‐year respiratory function were similar between groups. Log‐rank analysis (median follow‐up 2.5 years) demonstrated similar patients’ survival (P = 0.439) and time free of chronic lung allograft disease (P = 0.484). The EVLP program increased by 16% the number of LuTX. Compared to standard donors, EVLP patients had worse respiratory function immediately after LuTX but similar early and mid‐term outcomes.
Despite significant improvements in lung transplantation procedures, the incidence of airway complications (ACs) remains high (2%-18%); these complications are associated with high costs, great ...morbidities, and a decreased quality of life. There is general disagreement over potential risk factors determining ACs, including graft cold ischemic time (CIT). The aim of this study was to evaluate the association between CIT and ACs.
All patients undergoing lung transplantation between January 2011 and December 2017 were evaluated. We excluded retransplantations and patients with 90-day mortality. Demographic and clinical data regarding donors, recipients, and surgical procedures were analyzed using propensity score weighted marginal Cox regression model.
Out of the 161 lung transplantations performed in the study timeframe, 147 fulfilled the inclusion criteria and supplied complete data to be analyzed. Median follow-up was 25.5 months (interquartile range = 35.2). Ten patients (6.8%) had late ACs; out of the 260 anastomoses considered, 14 proved to be complicated (5.4%). Median time to event was 5.5 months (range, 3-15). ACs were classified as bronchial stenosis (12) and malacia (2). Mean CIT was 446.6 minutes (range, 117-1200). Without considering time-to-event data, CIT was significantly higher in complicated anastomoses (P = .002). The unweighted marginal univariate Cox model showed a significant association between ACs and CIT (P < .001). The propensity score weighted marginal univariable Cox model confirmed this significant association (P < .001).
The prolonged CIT time seems to be a risk factor for the development of late ACs; we endorse any measure that could limit CIT within 600 minutes.
•Airway complications are still regarded as a major problem in lung transplantation.•Prolonged cold ischemic time seems to be a risk factor for late airway complications after lung transplantations.•Cold ischemic time should be limited to 600 minutes to prevent airway complications.
The acceptable duration of donor warm ischemia time (DWIT) after cardiocirculatory death (DCD) is still debated. We analyzed the biomolecular profile and function during ex vivo lung perfusion (EVLP) ...of DCD lungs and their correlation with lung transplantation (LuTx) outcomes. Donor data, procurement times, recipient outcomes, and graft function up to 1 year after LuTx were collected. During EVLP, the parameters of graft function and metabolism, perfusate samples to quantify inflammation, glycocalyx breakdown products, coagulation, and endothelial activation markers were obtained. Data were compared to a cohort of extended-criteria donors after brain death (EC-DBD). Eight DBD and seven DCD grafts transplanted after EVLP were analyzed. DCD's DWIT was 201 188;247 minutes. Donors differed only regarding the duration of mechanical ventilation that was longer in the EC-DBD group. No difference was observed in lung graft function during EVLP. At reperfusion, "wash-out" of inflammatory cells and microthrombi was predominant in DCD grafts. Perfusate biomolecular profile demonstrated marked endothelial activation, characterized by the presence of inflammatory mediators and glycocalyx breakdown products both in DCD and EC-DBD grafts. Early graft function after LuTx was similar between DCD and EC-DBD. DCD lungs exposed to prolonged DWIT represent a potential resource for donation if properly preserved and evaluated.
Lung transplantation is the only therapeutic option for end-stage pulmonary failure. Nevertheless, the shortage of donor pool available for transplantation does not allow to satisfy the requests, ...thus the mortality on the waiting list remains high. One of the tools to overcome the donor pool shortage is the use of
lung perfusion (EVLP) to preserve, evaluate and recondition selected lung grafts not otherwise suitable for transplantation. EVLP is nowadays a clinical reality and have several destinations of use. After a narrative review of the literature and looking at our experience we can assume that one of the chances to improve the outcome of lung transplantation and to overcome the donor pool shortage could be the tissue regeneration of the graft during EVLP and the immunomodulation of the recipient. Both these strategies are performed using mesenchymal stem cells (MSC). The results of the models of lung perfusion with MSC-based cell therapy open the way to a new innovative approach that further increases the potential for using of the lung perfusion platform.
Non-typhoid Salmonella (NTS) is an important cause of bacterial meningitis in newborn and infants in developing countries, but rarely in industrialized ones. We describe an unusual presentation of ...bacterial meningitis in an infant, focusing on his diagnostic and therapeutic management.
An Italian two-month old male presented high fever and diarrhea with blood, associated with irritability. Inflammatory markers were high, cerebrospinal fluid analysis was compatible with bacterial meningitides but microbiological investigations were negative. Salmonella enteritidis was isolated from blood. Cerebral ultrasound and MRI showed periencephalic collection of purulent material. Specific antibiotic therapy with cefotaxime was initiated with improvement of clinical conditions and blood tests. Brain MRI follow up improved progressively.
Most of pediatric patients with NTS infection develop self-limited gastroenteritis, but in 3-8% of the cases complications such as bacteremia and meningitis may occur, especially in weak patients. Cerebral imaging can be useful to identify neurological findings. Although there is no standardized treatment for this condition, specific antibiotic therapy for at least four weeks is recommended. Neuroimaging follow up is required due to high risk of relapse.
BACKGROUND Hypothermic machine perfusion (HMP) appears to exert a reconditioning effect on the ischemic damage of kidney grafts. However, some concerns still remain about its real effectiveness when ...it is delayed after a preliminary period of static cold storage (SCS) or with prolonged overall cold ischemia time (CIT). MATERIAL AND METHODS The effect of HMP on hemodynamic, metabolic, histological and ultrastructural features of grafts was investigated in 21 single-kidney grafts treated with a delayed HMP after SCS and with a total CIT of over 24 h. RESULTS The mean CIT, SCS, and HMP times were 29 h, 12 h, and 18 h, respectively. Longer SCS was associated with higher vascular resistance and lower arterial flow. In the pre- vs. post-HMP comparison, a significant decrease in arterial resistances and increase of flow were recorded. The hemodynamic improvement was independent of HMP duration. The perfused grafts retained some metabolic activity, with a statistically significant decrease of pH, pO2, and glucose levels, and increase of lactates in the perfusion liquid, by the end of HMP. Longer SCS was associated with higher pH and greater pO2 decrease during HMP. Light microscopy and transmission electronic microscopy revealed no significant variations in nuclear, cytoplasmic, or ultrastructural damage. SCS, HMP, and CIT were not identified as risk factor for delayed graft function or rejection. CONCLUSIONS A delayed and extended HMP can recover the graft hemodynamic function, maintain some metabolic activity, and stabilize the accumulated ischemic damage due to a preliminary SCS.
The role of S1P in Cystic Fibrosis (CF) has been investigated since 2001, when it was first described that the CFTR channel regulates the inward transport of S1P. From then on, various studies have ...associated F508del CFTR, the most frequent mutation in CF patients, with altered S1P expression in tissue and plasma. We found that human bronchial epithelial immortalized and primary cells from CF patients express more S1P than the control cells, as evidenced by mass spectrometry analysis. S1P accumulation relies on two- to four-fold transcriptional up-regulation of SphK1 and simultaneous halving of SGPL1 in CF vs. control cells. The reduction of SGPL1 transcription protects S1P from irreversible degradation, but the excessive accumulation is partially prevented by the action of the two phosphatases that are up-regulated compared to control cells. For the first time in CF, we describe that Spns2, a non-ATP dependent transporter that normally extrudes S1P out of the cells, shows deficient transcriptional and protein expression, thus impairing S1P accrual dissipation. The in vitro data on CF human bronchial epithelia correlates with the impaired expression of Spns2 observed in CF human lung biopsies compared to healthy control.
The majority of patients with non-small cell lung cancer (NSCLC) develop distant metastases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are capable of reducing brain and ...adrenal metastases. However, the EGFR status may be discordant between primary NSCLC and the corresponding metastases.
Using fluorescence in situ hybridization (FISH) analysis, the EGFR gene status was evaluated in a series of 38 cerebral or adrenal metastases collected from two institutions and in the corresponding primary tumors. Also, EGFR mutational analysis was performed using direct sequencing on the cerebral metastases.
EGFR FISH was positive in 28% of the primary tumors and in 45% of the metastases (p < 0.05). Among the seven cases FISH-positive at the metastatic site but negative in the primary tumor, six were brain metastases, and one was an adrenal metastasis; all were polysomic for chromosome 7, none were amplified. No EGFR mutations have been found in the cerebral metastases.
Because the molecular asset of EGFR may change during the metastatic progression of NSCLC to brain (but not to adrenal), the selection of patients with brain metastasis for specific targeted therapies by EGFR FISH analysis should be performed on metastatic lesions rather than on their corresponding primary tumors.
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