Optimizing SARS-CoV-2 vaccine responses in kidney transplant recipients: an urgent need.

Kidney transplant recipients (KTRs) have been identified as a population at increased risk for severe SARS-CoV-2 infection outcomes. This study focused on understanding the immune response of KTRs post-vaccination, specifically examining both serological and cellular responses to the SARS-CoV-2 vaccine. Thirteen individuals, including seven KTRs and six healthy donors, were evaluated for antibody levels and T cell responses post-vaccination. The study revealed that KTRs had significantly lower serological responses, including reduced anti-receptor binding domain (RBD) binding antibodies and neutralizing antibodies against the Wuhan, Delta, and Omicron BA.2 strains. Additionally, KTRs demonstrated weaker CD8 T cell cytotoxic responses and lower Th1 cytokine secretion, particularly IFN-γ, after stimulation with variant spike peptide pools. These findings highlight the compromised immunity in KTRs post-vaccination and underscore the need for tailored strategies to bolster immune responses in this vulnerable group. Further investigations are warranted into the mechanisms underlying reduced vaccine efficacy in KTRs and potential therapeutic interventions. IMPORTANCE: Some studies have revealed that KTRs had lower serological response against SARS-CoV-2 than healthy people. Nevertheless, limited studies investigate the cellular response against SARS-CoV-2 in KTRs receiving SARS-CoV-2 vaccines. Here, we found that KTRs have lower serological and cellular responses. Moreover, we found that KTRs had a significantly lower IFN-γ secretion than healthy individuals when their PBMCs were stimulated with SARS-CoV-2 spike peptide pools. Thus, our findings suggested that additional strategies are needed to enhance KTR immunity triggered by the vaccine.

Humoral responses to multiple SARS-CoV-2 variants after two doses of vaccine in kidney transplant patients.

Background: The COVID-19 pandemic has led to millions of fatalities globally. Kidney transplant (KT) patients, given their comorbidities and under immunosuppressant drugs, are identified as a high-risk group. Though vaccination remains pivotal for pandemic control, some studies indicate that KT exhibits diminished immune reactions to SARS-CoV-2 vaccines. Therefore, evaluating the vaccine responses in KT, especially the humoral responses against emergent variants is crucial.Methods: We developed a multiplexed SARS-CoV-2 variant protein microarray, incorporating the extracellular domain (ECD) and the receptor binding domain (RBD) of the spike proteins from the variants. This was employed to investigate the collective humoral responses after administering two doses of mRNA-1273 and AZD1222 vaccines in KT under immunosuppressive drugs and in healthy controls.Results: After two doses of either mRNA-1273 or AZD1222, the KT generally showed lower surrogate neutralizing and total antibodies against spike ECD in multiple variants compared to healthy controls. Although two doses of mRNA-1273 induced 1.5-2 fold more surrogate neutralizing and total antibodies than AZD1222 in healthy controls, the KT subjects with two doses of mRNA-1273 generally exhibited higher surrogate neutralizing but similar total antibodies against spike ECD in multiple variants. There were moderate to high correlations between the surrogate neutralizing and total antibodies against spike ECDs.Conclusion: This study offers pivotal insights into the relative vulnerability of KT concerning humoral immunity and the evolving mutations of SARS-CoV-2. Such findings are useful for evaluating vaccine responses and recommending vaccine episodes for KT.

Prediction of surgical outcomes in severe encapsulating peritoneal sclerosis using a computed tomography scoring system.

BACKGROUND/PURPOSE: Encapsulating peritoneal sclerosis (EPS) is a rare and potential lethal complication of peritoneal dialysis characterized by bowel obstruction. Surgical enterolysis is the only curative therapy. Currently, there are no tools for predicting postsurgical prognosis. This study aimed to identify a computed tomography (CT) scoring system that could predict mortality after surgery in patients with severe EPS. METHODS: This retrospective study enrolled patients with severe EPS who underwent surgical enterolysis in a tertiary referral medical center. The association of CT score with surgical outcomes including mortality, blood loss, and bowel perforation was analyzed. RESULTS: Thirty-four patients who underwent 37 procedures were recruited and divided into a survivor and non-survivor group. The survivor group had higher body mass indices (BMIs, 18.1 vs. 16.7 kg/m2, p = 0.035) and lower CT scores (11 vs. 17, p < 0.001) than the non-survivor group. The receiver operating characteristic curve revealed that a CT score of ≥15 could be considered a cutoff point to predict surgical mortality, with an area under the curve of 0.93, sensitivity of 88.9%, and specificity of 82.1%. Compared with the group with CT scores of <15, the group with CT scores of ≥15 had a lower BMI (19.7 vs. 16.2 kg/m2, p = 0.004), higher mortality (4.2% vs. 61.5%, p < 0.001), greater blood loss (50 vs. 400 mL, p = 0.007), and higher incidence of bowel perforation (12.5% vs. 61.5%, p = 0.006). CONCLUSION: The CT scoring system could be useful in predicting surgical risk in patients with severe EPS receiving enterolysis.

Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study.

OBJECTIVE: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study. METHODS: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids. RESULTS: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm. CONCLUSION: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).

A simple and novel technique for training in microvascular suturing in a rat model.

BACKGROUND: Though microvascular clamps are widely used for anastomosis training, there still have several shortcomings, including the bulging, expensiveness and unavailability due to sterilization. The aim of this study is to introduce a simple and novel microvascular training model without use of microvascular clamps. METHODS: Femoral vessels of Sprague Dawley rats training model were used to evaluate the usefulness of 4-0 silk as a slipknot for performing arterio-arterial and veno-venous microvascular anastomoses. A total of 12 Sprague Dawley rats were randomly assigned to either slipknot group or vascular clamp group. We also assess other endpoints, including ischemic time, patency rate, and clinical features. An additional histological study was performed to compare their immediate traumatic effects on vessel wall. RESULTS: There was no ischemic change or congestive sign in the lower limb after microvascular anastomosis. The total warm ischemic time for the vascular anastomosis was not significantly different. We performed the patency test immediately after microvascular anastomosis and one week after surgery. No intraoperative vascular bleeding was found during these procedures and no thrombosis occurred postoperatively. The histologic damages to occluded area were not significantly different in both groups. CONCLUSION: We demonstrate a microsurgical suture technique performed without any vascular clamp on a rat model. This rat model was designed for training in the technique of microvascular anastomosis. Compared with microvascular clamps, silk slipknot is a cheap, easily available, less space-occupying technique while performing microvascular anastomoses training. This preliminary study provides a simple and effective alternative method for microvascular anastomosis training.

Community-onset bacteremia in kidney transplant recipients: The recipients fare well in terms of mortality and kidney injury.

BACKGROUND: Bloodstream infection is not uncommon in kidney transplant recipients (KTRs) and is associated with mortality, graft loss, and increased medical expenses. Whether these septic patients are more vulnerable to serious complications, resistant strains, or worse clinical outcomes than other patient groups in the community-onset settings remains undetermined. METHODS: A retrospective study was conducted at a medical center in southern Taiwan. Community-onset bacteremia in the KTRs and a control population at the emergency department were identified. Demographic data, clinical characteristics, bacteremic pathogens, antimicrobial resistance, and clinical outcomes were recorded. RESULTS: Forty-one bacteremic episodes in the KTRs and 82 episodes in control patients were studied. The KTR group had younger age, fewer malignancies, more urosepsis (61% vs. 22%, p = 0.004), and fewer biliary tract infections (0% vs. 13.4%, p = 0.018). Escherichia coli was the most commonly isolated pathogen in both the groups (51.2% and 41.5%, respectively). No Klebsiella pneumoniae bacteremia was noted in the KTRs, compared with 14 (17.1%) episodes in the control group (p = 0.010). Antimicrobial resistance profiles of bacteremic pathogens were similar (all p > 0.6). The KTRs with community-onset bacteremia did not have a worse outcome (in-hospital mortality rate: 2.4% vs. 10%, p = 0.172) nor more incomplete resolution of kidney injury after acute kidney injury events (21.1% vs. 25%, p > 0.99) than the control group. CONCLUSION: KTRs with community-onset bacteremia did not fare worse in terms of clinical outcome and kidney injury.

Cutaneous alternariosis in a renal transplant recipient: a case report and literature review.

Organ transplant recipients under immunosuppressive therapy have a highly increased risk of acquiring unusual opportunistic infections. Diagnosis of the etiology of infection may be difficult in clinical manifestations, which need further histological and biological investigations. We recently treated a male renal transplant recipient with a cutaneous phaeohyphomycosis due to Alternaria species. The diagnosis was based on microscopy and culture of the skin lesions. Treatment with oral itraconazole for 5 weeks was ineffective, then clinical improvement was achieved by combination of amphotericin B wet-packing and systemic antifungal therapy with oral voriconazole. Alternaria species are ubiquitous plant-inhabiting saprobes, which are increasingly associated with opportunistic phaeohyphomycosis in immunocompromised individuals. To the best of our knowledge, this is the second case report noting sporotrichoid pattern as the manifestation of cutaneous alternariosis. In this context, we reviewed recent renal-transplant-related cutaneous alternariosis reported in the English-language literature during 1995 to 2011 to summarize its clinical features and outcomes, and to guide clinicians in the care of kidney transplant patients with cutaneous alternariosis.

Preconditioning renoprotective effect of isoflurane in a rat model of virtual renal transplant.

BACKGROUND: The development of warm-cold ischemia-reperfusion (IR) injury of the kidney grafts is inevitable during renal transplantation. However, there is currently no definite renoprotective strategy available in the protection of the graft tissue. In the present study, we compared the renal protection of preconditioning isoflurane with N-acetylcysteine (NAC) in a novel rat model of warm-cold renal IR injury. MATERIALS AND METHODS: Adult Sprague-Dawley rats were randomly assigned to receive inhaled isoflurane (1.5% for 2 h), NAC (1 g/kg, intra-arterial injection) or placebo before the induction of brief warm ischemia (10 min) followed by cold ischemia (45 min) periods. Plasma levels of creatinine and tissue inflammatory reaction in the kidney were analyzed 72 h after reperfusion. RESULTS: Elevated plasma level of creatinine and urea indicated the development of acute renal injury secondary to IR injury. The creatinine levels were reduced in animals pretreated with inhaled isoflurane and NAC, and the level was more significantly decreased in the isoflurane-treated group. Preconditioning with volatile isoflurane also significantly suppressed the tissue myeloperoxidase activity and expression of the inducible nitric oxide synthase. Immunostaining confirmed that myeloperoxidase expression was most significantly attenuated in the glomerulus and peritubular capillaries of rats pre-exposed to isoflurane. CONCLUSIONS: We present the first study demonstrating that the administration of volatile isoflurane before induction of experimental warm-cold renal IR injury provides preconditioning renoprotective effect, which is superior to the treatment with NAC. The beneficial renoprotective effect of isoflurane is most likely mediated by attenuation of proinflammatory reaction in the injured kidney.

Development of laparoscopic donor nephrectomy: a strategy to increase living kidney donation incentive and maintain equivalent donor/recipient outcome.

BACKGROUND/PURPOSE: Laparoscopic donor nephrectomy (LDN) has emerged as the preferred technique worldwide, and has contributed to a dramatic increase in living kidney donation during the past decade. We adopted LDN in 2002 with the intention of increasing living kidney donation incentive and maintaining equivalent donor/recipient outcome. METHODS: Forty-five LDNs were performed between September 2002 and November 2007. Donor demographics, operative characteristics, perioperative complications and donor/recipient outcome were reviewed retrospectively. The LDN series was divided into earlier and later groups for comparison. To confirm the safety and efficacy of LDN, we compared the results with those of previous series and our open donor nephrectomy (ODN) series. RESULTS: All 45 LDN kidneys were procured and transplanted successfully. Mean donor operation time was 327.7+/-10.2 minutes, blood loss was 286.0+/-48.3 mL, and warm ischemia time was 233.9+/-19.6 seconds. Two (4.4%) open conversions happened in the earlier group. There was a significant decrease in warm ischemia time and donor intraoperative complications in the later group. There was no donor mortality and there were no repeat surgical procedures. Delayed graft function occurred in 8.9% of cases and three (6.7%) recipients developed ureteral complications. All but one recipient was discharged with adequate renal function. Graft function continued in 41 of the 43 harvested kidneys (95.3%). Compared with ODN, there was a significant decrease in donor postoperative stay in the LDN series (p=0.00). There was no difference between the series with regard to donor safety, donor outcome, and immediate and long-term recipient outcome. CONCLUSION: The number of living kidney donations increased significantly after adopting LDN in our series. The equivalent donor/recipient outcome of the LDN series compared with that of previous and ODN series was achieved with increasing experience.

Craniofacial gunshot injury resulting in pseudoaneurysm of the left internal maxillary artery and Collet-Sicard syndrome.

Facial gunshot is a challenging medico-surgical emergency because of the complex neurovascular structure in the area. We present a patient who sustained a facial gunshot injury, with massive nasal and oral bleeding that resulted in shock. We review the management of gunshot injury to the internal maxillary artery, both in acute and chronic stages. In addition, we describe the clinical course of the rarely occurring Collet-Sicard syndrome, which involves injury to the 9th, 10th, 11th, and 12th cranial nerves associated with gunshot injury.

A review of obturator hernia and a proposed algorithm for its diagnosis and treatment.

The aim of this article is to provide a review of six patients with the various stages of obturator hernia and a diagnostic and therapeutic strategy in suspected cases. Obturator hernia is relatively rare and is a diagnostic challenge. It is a significant cause of intestinal obstruction, especially in emaciated elderly women with chronic disease. A palpable groin mass is not common in these patients because the hernia mass is usually concealed beneath the pectineus muscle. The high mortality is directly related to the delayed recognition, with resultant ruptured gangrenous bowel, and to the high incidence of patients with concurrent medical illness. A total of six patients with obturator hernias were treated at this hospital between 1994 and 2004, and one of these patients was diagnosed and treated by elective laparoscopy. We reviewed these six cases and examined the clinical presentation, age, body weight, associated medical conditions, preoperative diagnosis, operative findings, complications, and outcome in this retrospective study. We concluded that we cannot shorten the time from onset of symptoms to admission, but what we can do is to make a rapid evaluation and surgical intervention to reduce the morbidity and mortality from obturator hernia. The approaches to different presentation of obturator hernia and diagnostic role of CT scan are also discussed.