Neurological complications of SARS-CoV-2 infection among solid organ transplanted patients: does immunosuppression matter?

Introduction: SARS-CoV-2 infection can lead to a broad range of neurological manifestations such as olfactory and gustative disorders, myalgias, headache, and fatigue but also more rare and severe neurological pictures such seizures, encephalitis, and cerebrovascular diseases. It is still unknown if the underlying pathophysiological mechanism is the direct cytotoxic effect of the virus on central nervous system or if the related systemic inflammation leads to cerebral suffering and neurological symptoms. Studying neurological manifestations of SARS-CoV-2 infection among solid organ transplant recipients, who take immunosuppressive drugs, may help to shed light on this topic. Methods: We enrolled a total of 73 solid organ transplantation recipients (kidney, liver, lung, heart and combined) with a history of SARS-CoV-2 infection (in the period between July 2020 and June 2021). We collected all demographic and clinical general information and, through phone interviews, we registered retrospectively the occurrence of neurological symptoms during the acute phase of infection and within the next 6 months. Results: Approximately 27.4% (20/73) of patients needed hospitalization during the infection, 25.3% (18/73) were treated with oxygen therapy, and only one patient was admitted to the Intensive Care Unit for mechanical ventilation. Almost 74% (54/73) of patients reported at least one neurological symptom/disease. The most frequent neurological complications were myalgia (57.5%), headache (37%), and hyposmia/hypogeusia (37%). Need of oxygen therapy during the SARS-CoV-2 infection was statistically significantly associated to neurological complications (p= 0.0344). Pre-infection neurological comorbidities and immunosuppression levels (higher levels of tacrolimus and also being on steroids) did not modify the probability to have neurological manifestations. Discussion: Frequency of headache was comparable with the same self-reported symptom in the general population, while hyposmia/hypogeusia was more frequent in our cohort of transplant recipients. Higher level of tacrolimus as well as being on steroids did not result protective against neurological manifestation. Lastly neurological symptoms occurred more frequent in more severe cases of infection.

Donor-derived carbapenem-resistant gram-negative bacterial infections in solid organ transplant recipients: Active surveillance enhances recipient safety.

Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile.

Risk factors for surgical site infection following cardiac surgery in a region endemic for multidrug resistant organisms.

OBJECTIVES: To identify risk factors for surgical site infections following cardiosurgery in an area endemic for multidrug resistant organisms. DESIGN: Single-center, historical cohort study including patients who underwent cardiosurgery during a 6-year period (2014-2020). SETTING: Joint Commission International accredited, multiorgan transplant center in Palermo, Italy. MAIN OUTCOME MEASURES: Surgical site infection was the main outcome. RESULTS: On a total of 3609 cardiosurgery patients, 184 developed surgical site infection (5.1 %). Intestinal colonization with multidrug resistant organisms was more frequent in patients with surgical site infections (69.6 % vs. 33.3 %; p < 0.001). About half of surgical site infections were caused by Gram-negative bacteria (n = 97; 52.7 %). Fifty surgical site infections were caused by multidrug resistant organisms (27.1 %), with extended-spectrum Beta-lactamase-producing Enterobacterales (n = 16; 8.7 %) and carbapenem-resistant Enterobacterales (n = 26; 14.1 %) being the predominant resistance problem. However, in only 24 of surgical site infections caused by multidrug resistant organisms (48 %), mostly carbapenem-resistant Enterobacterales (n = 22), a pathogen match between the rectal surveillance culture and surgical site infections clinical culture was demonstrated. Nevertheless, multivariate logistic regression analysis identified a rectal swab culture positive for multidrug resistant organisms as an independent risk factor for SSI (odds ratio 3.95, 95 % confidence interval 2.79-5.60). Other independent risk factors were female sex, chronic dialysis, diabetes mellitus, previous cardiosurgery, previous myocardial infarction, being overweight/obese, and longer intubation time. CONCLUSION: In an area endemic for carbapenem-resistant Enterobacterales, intestinal colonization with multidrug resistant organisms was recognized as independent risk factor for surgical site infections. IMPLICATIONS FOR CLINICAL PRACTICE: No causal relationship between colonization with resistant pathogens and subsequent infection could be demonstrated. However, from a broader epidemiological perspective, having a positive multidrug resistant organisms colonization status appeared a risk factor for surgical site infections. Therefore, strict infection control measures to prevent cross-transmission remain pivotal (e.g., nasal decolonization, hand hygiene, and skin antisepsis).

Cognitive outcomes in patients treated with neuromuscular electrical stimulation after coronary artery bypass grafting.

Objective: Mechanisms of neurocognitive injury as post-operative sequelae of coronary artery bypass grafting (CABG) are not understood. The systemic inflammatory response to surgical stress causes skeletal muscle impairment, and this is also worsened by immobility. Since evidence supports a link between muscle vitality and neuroprotection, there is a need to understand the mechanisms by which promotion of muscle activity counteracts the deleterious effects of surgery on long-term cognition. Methods: We performed a clinical trial to test the hypothesis that adding neuromuscular electrical stimulation (NMES) to standard rehabilitation care in post-CABG patients promotes the maintenance of skeletal muscle strength and the expression of circulating neuroprotective myokines. Results: We did not find higher serum levels of neuroprotective myokines, except for interleukin-6, nor better long-term cognitive performance in our intervention group. However, a greater increase in functional connectivity at brain magnetic resonance was seen between seed regions within the default mode, frontoparietal, salience, and sensorimotor networks in the NMES group. Regardless of the treatment protocol, patients with a Klotho increase 3 months after hospital discharge compared to baseline Klotho values showed better scores in delayed memory tests. Significance: We confirm the potential neuroprotective effect of Klotho in a clinical setting and for the first time post-CABG.

Continuous Renal Replacement Therapy after Liver Transplantation: Peri-Operative Associated Factors and Impact on Survival.

Continuous renal replacement therapy (CRRT) following orthotopic liver transplantation (OLT) is usually started for multifactorial reasons, with variable incidence among series. This paper presents a single-center retrospective observational study on the early use (within one week) of CRRT after consecutive cadaveric OLT from January 2008 to December 2016. Preoperative patient characteristics and intraoperative data were collected, and patients were divided into two groups (CRRT and no CRRT) to explore the factors associated with the use of CRRT. Repeated measurements of postoperative creatinine were analyzed with generalized estimating equation (GEE) models. Among 528 OLT patients, 75 (14.2%) were treated with CRRT at least once in the first week. Patients treated with CRRT showed lower survival in a Kaplan−Meier curve (log-rank p value < 0.01). Patients treated with CRRT had a more severe preoperative profile, with a significantly higher age, MELD, BUN, creatinine, and total bilirubin, as well as a longer surgery time and a higher number of transfusions of red blood cells, plasma, and platelets (all p values < 0.05). In a stepwise multiple analysis, the following characteristics remained independently associated with the use of CRRT: the MELD score OR 1.12 (95% CL: 1.07−1.16), p value < 0.001, and the preoperative value for blood urea nitrogen OR 1.016 (95% CL: 1.010−1.023), p value < 0.001. The early use of CRRT after OLT occurred at a low rate in this large cohort; however, it was associated with worse outcomes. Apart from the preoperative severity, repeated intraoperative hypotension episodes, which were likely modifiable or preventable, were associated with the increased use of CRRT and higher postoperative creatinine.

Donor Simvastatin Treatment Is Safe and Might Improve Outcomes After Liver Transplantation: A Randomized Clinical Trial.

BACKGROUND: The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study. METHODS: SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective tial aiming to compare the safety and efficacy of preoperative brain-dead donors' treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d posttransplant; secondary end-points were severe complications. RESULTS: The trial enrolled 58 adult patients (18-65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% ( P = 0.016) and 89.66% ( P = 0.080) at 90 d and 86.21% ( P = 0.041) and 86.2% ( P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group ( P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d ( P = 0.017), ( P = 0.015) in the simvastatin group. CONCLUSIONS: Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory.

Neurological Screening in Elderly Liver Transplantation Candidates: A Single Center Experience.

BACKGROUND: Cerebral small vessels disease (cSVD) is an age-related disorder and risk factor for stroke and cognitive/motor impairments. Neurological complications (NCs) are among the causes of adverse outcomes in older liver transplant recipients. This study sought to determine whether cSVD predicts acute NCs in over 65-year-old liver transplant patients. METHODS: Data were collected, from a retrospective medical chart review, of 22 deceased donor liver transplant recipients aged 65 years or older with a pre-operative brain magnetic resonance imaging (MRI). We used the Fazekas score (0-3) as a quantitative measurement of the vascular lesion load seen in the MRI. We analyzed all post-operative acute NCs occurring during the hospital stay and any other non-NC. RESULTS: cSVD was recognized in all patients. Neurological complications (NCs) occurred in 18.1% of patients with toxic-metabolic encephalopathy the most frequent diagnosis (13.64%). More severe cSVD was associated with seizures (p = 0.0362), longer hospital stay (p 0.0299), and disability (p 0.0134). In our elderly cohort, hepatic encephalopathy (HE) (p 0.0287) and ascites (p 0.0270) were predictors of NCs after liver transplantation. Ascites and/or variceal bleeding and severity of liver disease were associated with adverse post-operative outcomes. The small sample size limited the statistical analysis power. CONCLUSIONS: We present the preliminary data of a single-center retrospective study aimed at understanding the cSVD role on NCs and non-NCs after a liver transplantation in elderly patients. This would encourage a more appropriate multicenter prospective study that will definitely confirm if a neurological screening in old age liver transplant candidates is appropriate.

Microbiological Surveillance of Endoscopes in a Southern Italian Transplantation Hospital: A Retrospective Study from 2016 to 2019.

Endoscopes are medical instruments that are used routinely in health structures. Due to their invasive nature and contact with many patients, they may cause hospital-acquired infections if not disinfected correctly. To ensure a high-level disinfection procedure or reprocessing, since the methods currently adopted in our institute are adequate, we evaluated retrospectively the presence of microorganisms in our endoscopes after reprocessing. Microbiological surveillance was performed from January 2016 to December 2019 in the instruments in use in our endoscopic room after reprocessing. In total, 35 endoscopes (3 duodenoscopes, 3 echoendoscopes, 12 bronchoscopes, 5 colonoscopes, and 12 gastroscopes) were evaluated for the presence of microorganisms, including multidrug-resistant pathogens and indicator microorganisms (IMOs). Our procedures were in agreement with an internal protocol based on Italian, international, and the Center for Disease Control and Prevention (CDC) recommendations. Of a total of 811 samples, 799 (98.5%) complied with the regulatory guidelines, while 9 (1.1%) were positive for IMOs, and 3 (0.4%) displayed more than 10 colony-forming units (CFU) of environmental and commensal pathogens. Our results show that the internal reprocessing protocol is very efficient, leading to a very low number of observed contaminations, and it could be easily implemented by other health facilities that face a huge number of hospital-acquired infections due to incorrectly disinfected endoscopes.

Human Amnion-Derived Mesenchymal Stromal Cells in Cirrhotic Patients with Refractory Ascites: A Possible Anti-Inflammatory Therapy for Preventing Spontaneous Bacterial Peritonitis.

Cirrhosis is associated with dysregulated immune cell activation and immune dysfunction. These conditions modify gut flora, facilitate bacterial translocation, and increase susceptibility to bacterial peritonitis and consequent systemic infections by dramatically affecting long-term patient survival. Human amnion-derived mesenchymal stromal cells (hA-MSCs) exert immunomodulatory potential benefit, and have the ability to modulate their actions, especially in situations requiring immune activation through mechanisms not fully understood. In this study, we aimed to investigate, in vitro, the immunostimulant or immunosuppressive effects of hA-MSCs on cellular components of ascitic fluid obtained from cirrhotic patients with refractory ascites. We found that hA-MSCs viability is not affected by ascitic fluid and, interestingly, hA-MSCs diminished the pro-inflammatory cytokine production, and promoted anti-inflammatory M2 macrophage polarization. Moreover, we found that there was no simultaneous significant decrease in the M1-like component, allowing a continual phagocytosis activity of macrophages and NK cells to restore a physiological condition. These data highlight the plasticity of hA-MSCs' immunomodulatory capacity, and pave the way to further understanding their role in conditions such as spontaneous bacterial peritonitis.

Steatosis affects the performance of liver stiffness measurement for fibrosis assessment in patients with genotype 1 chronic hepatitis C.

BACKGROUND & AIMS: In Chronic Hepatitis C (CHC), the influence of steatosis on liver stiffness measurement (LSM) is still debated. We assessed the impact of steatosis and its ultrasonographical sign - bright liver echo pattern (BLEP) - on LSM values and on transient elastography (TE) accuracy for the diagnosis of liver fibrosis, in a cohort of consecutive patients with Genotype 1 (G1) CHC. METHODS: Patients (n=618) were assessed by clinical, ultrasonographic and histological (Scheuer score) features. TE was performed using the M probe. RESULTS: Male gender (p=0.04), steatosis as continuous variable (p<0.001), severity of necroinflammation (p=0.02) and stage of fibrosis (p<0.001) were associated with LSM by multivariate linear regression analysis. Among patients within the same fibrosis stages (F0-F2 and F3-F4; F0-F3 and F4), mean LSM values, expressed in kPa, were significantly higher in subjects with moderate-severe steatosis (⩾20% at liver biopsy) compared with those without, as well as in patients with BLEP on US compared with their counterpart. In subjects without severe fibrosis (F0-F2) and without cirrhosis (F0-F3), a higher rate of false-positive LSM results was observed in patients with steatosis ⩾20% compared with those without (F0-F2: 35.3% vs. 17.9%; F0-F3: 38.9% vs. 16.6%), and in patients with BLEP on US (F0-F2: 28.0% vs. 18.3%; F0-F3: 29.7% vs. 17.8%) compared with their counterpart. CONCLUSIONS: In patients with G1 CHC, the presence of moderate-severe steatosis, detected by histology or by US, should always be taken into account in order to avoid overestimations of liver fibrosis assessed by TE.