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Programmed-cell death protein 1 (PD-1) inhibitors have emerged as a standard of care treatment among advanced-stage or metastatic cutaneous squamous cell carcinoma (cSCC). Immune-compromised patients and particularly solid organ transplant recipients (SOTRs) are considered at high risk for cSCC. When treated with PD-1 inhibitors, the possibility of organ rejection, autoimmune flare, or insufficient response to treatment is feared. As these patients were excluded from past prospective clinical trials, we aim to describe our institute's experience regarding these patients. A retrospective analysis was conducted on cSCC patients treated with PD-1 inhibitors. Comparisons were made between immune-compromised and immune-competent groups, with a subgroup analysis of SOTR. The study cohort comprised of 133 patients, including 97.8% receiving Cemiplimab with a mean age of 77.2 ± 11.7 years. Immune-compromised patients constituted 26.9% (n = 35) of the cohort, including 10 SOTR (all kidney transplant recipients). Objective response rates (ORRs) and disease control rates (DCR) were comparable between immunocompetent and immunosuppressed patients receiving Cemiplimab (ORR: 76.8% vs 62.9%, P = .12; DCR: 81.1% vs 68.6%, P = .13). SOTR demonstrated an 80% ORR and DCR. Progression-free survival was comparable across all groups. Toxicity rates were similar between immunosuppressed and immunocompetent subgroups (68.6% vs 62.1%, P = .5). Two OTRs (20%) experienced acute graft rejection. PD-1 inhibitors demonstrate efficacy and safety in immunosuppressed cSCC patients. While effective in SOTR, treatment requires multidisciplinary management due to the potential risk of organ rejection. These findings provide valuable insights into this understudied population and support the use of PD-1 inhibitors in immunosuppressed patients with advanced cSCC.

Mycobacterium abscessus complex (MABC), a rapidly growing Mycobacterium, is one of the most common causes of non-tuberculous mycobacteria (NTM) infections in the United States of America, and it has been associated with a wide spectrum of infections in immunocompetent and immunosuppressed individuals. Eradicating MABC is very challenging, even with prolonged combination therapies. The management of MABC infections in solid organ transplant (SOT) patients is usually complex given their net state of immunosuppression, associated comorbidities, and potential drug–drug interactions, among other things. In this manuscript, we discussed the antimicrobial management of pulmonary and extrapulmonary MABC infections. In addition, we reviewed promising novel therapies such as clofazimine, omadacycline, bedaquiline, and inhaled tigecycline that could join the existing antimicrobial armamentarium to fight this infection associated with significant morbidity and mortality. However, further studies are needed, especially among the immunocompromised host.

The Severe Acute Respiratory Syndrome Coronavirus 2 is a recent disease that originated in China by the end of 2019. The origins of the dis-ease can be traced to bats, but it has been transmitted to humans, and the inter-human transmission is particularly rampant which has led to a pandemic of unseen proportions. The organ principally involved is the lungs, and severe pneumonia with lack of oxygen leads to fatalities. The aim of this review was to study the involvement of the kidneys with regard to COVID-19 infection and how the disease may affect people on hemodialysis or those who have undergone a kidney transplant. Indeed, the virus, in addition to the lungs, may affect other vascularized organs to a common receptor on lung epithelium and the endothelium of any organ. The kidney, which has a large endothelium surface, is affected, and COVID-19 may lead to acute renal failure. On the other hand, the virus may easily spread among people who are on hemodialysis three times a week. People on hemodialysis may have low immunity, and the virus may have dangerous effects on such people. Finally, renal transplant patients may be easily affected, and the virus may have severe consequences, even death. We will summarize the principal prophylactic measures to be adopted and the therapeutic measures available. Clearly due to the recent occurrence of the pandemic the majority these measures lack a basis in evidence-based medicine and only highlight the efforts to limit COVID-19 induced damage.

Resistant CMV infections are challenging complications after SOT and HSCT. Prompt recognition of ARMs is imperative for appropriate therapy. 108 plasma samples from 96 CMV + transplant recipients with suspected resistance were analysed in CNM in a retrospective nationwide study from January 2018 to July 2022 for resistance genotyping. ARMs in UL97 and UL54 were found in 26.87% (18/67) and 10.60% (7/66) of patients, respectively. Patients’ ARM distribution in UL97 was as follows: L595S n = 3; L595S/M460I n = 1; L595S/N510S n = 1; L595W n = 1; C603W n = 4; A594V n = 3; A594E n = 1; C607Y n = 1; L397R/T409M/H411L/M460I n = 1; L397I n = 1; H520Q n = 1; four patients showed ARMs in UL54 as well (F412C n = 1; T503I n = 2; P522S n = 1), whereas three patients exhibited ARMs in UL54 only (L501I/T503I/L516R/A834P n = 1; A987G n = 2). L516R in UL54 and L397R/I and H411L in UL97 have been found for the first time in a clinical sample. L595S/W was the most prevalent ARM found to lend resistance to GCV. In UL54 all ARMs lent resistance to GCV and CDV. In addition, A834P, found in one patient, also lent resistance to FOS. CMV load did not differ significantly in patients with or without ARMs, and no differences were found either between patients with ARMs in UL97 or in UL97 and UL54. Despite extensive use of classical antivirals for the treatment of CMV infection after HSCT and SOT, ARMs occurred mainly in viral UL97 kinase, which suggests that CDV and mostly FOS continue to be useful alternatives to nucleoside analogues after genotypic detection of ARMs.

Immunocompromised individuals are at high risk of severe illness and complications from influenza infection. For this reason, immunization using inactivated influenza vaccines is recommended for transplant patients, individuals receiving immunosuppressant treatments, and other persons with immunodeficiency. However, these immunocompromised populations are more likely to have lower and non-protective responses to annual vaccination with a standard influenza vaccine. Here, we review strategies aimed to improve the immunogenicity of influenza vaccines in immunocompromised populations. The different strategies employed have included adjuvanted vaccines, high-dose vaccines, booster doses, intradermal vaccination, and temporary discontinuation of immunosuppressant treatment regimens. High-dose trivalent, inactivated, split-virus influenza vaccine (IIV3-HD) is so far one of the leading strategies for improving vaccine responses in HIV patients, transplant patients, and persons receiving immunosuppressant therapies for inflammatory diseases. Several studies in these populations have shown stronger humoral responses with IIV3-HD than existing standard-dose trivalent vaccine, and comparable safety. Accordingly, some scientific societies have stated that high-dose influenza vaccine could be a preferred option for immunocompromised patients. However, larger randomized controlled studies are needed to validate relative immunogenicity and safety of IIV3-HD and other enhanced vaccines and vaccination strategies in immunocompromised individuals.

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017-2019, then became detectable at low levels in September 2020 and peaked at very high titers (10 genome copies/mL) in January 2022. In March 2022, we found >10 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.

Background: Using technology to reduce the pressure on the National Health Service (NHS) in England and Wales is a key government target, and the NHS Long-Term Plan outlines a strategy for digitally enabled outpatient care to become mainstream by 2024. In 2020, the COVID-19 response saw the widespread introduction of remote consultations for patient follow-up, regardless of individual preferences. Despite this rapid change, there may be enduring barriers to the effective implementation of remote appointments into routine practice once the unique drivers for change during the COVID-19 pandemic no longer apply, to which pre-COVID implementation studies can offer important insights. Objective: This study aims to evaluate the feasibility of using real-time remote consultations between patients and secondary care physicians for routine patient follow-up at a large hospital in the United Kingdom and to assess whether patient satisfaction differs between intervention and usual care patients. Methods: Clinically stable liver transplant patients were randomized to real-time remote consultations in which their hospital physician used secure videoconferencing software (intervention) or standard face-to-face appointments (usual care). Participants were asked to complete postappointment questionnaires over 12 months. Data were analyzed on an intention-to-treat basis. The primary outcome was the difference in scores between baseline and study end by patient group for the three domains of patient satisfaction (assessed using the Visit-Specific Satisfaction Instrument). An embedded qualitative process evaluation used interviews to assess patient and staff experiences. Results: Of the 54 patients who were randomized, 29 (54%) received remote consultations, and 25 (46%) received usual care (recruitment rate: 54/203, 26.6%). The crossover between study arms was high (13/29, 45%). A total of 129 appointments were completed, with 63.6% (82/129) of the questionnaires being returned. Patient satisfaction at 12 months increased in both the intervention (25 points) and usual care (14 points) groups. The within-group analysis showed that the increases were significant for both intervention (P<.001) and usual care (P=.02) patients; however, the between-group difference was not significant after controlling for baseline scores (P=.10). The qualitative process evaluation showed that—according to patients—remote consultations saved time and money, were less burdensome, and caused fewer negative impacts on health. Technical problems with the software were common, and only 17% (5/29) of patients received all appointments over video. Both consultants and patients saw remote consultations as positive and beneficial. Conclusions: Using technology to conduct routine follow-up appointments remotely may ease some of the resource and infrastructure challenges faced by the UK NHS and free up clinic space for patients who must be seen face-to-face. Our findings regarding the advantages and challenges of using remote consultations for routine follow-ups of liver transplant patients have important implications for service organization and delivery in the postpandemic NHS. Trial Registration: ISRCTN Registry 14093266; https://www.isrctn.com/ISRCTN14093266 International Registered Report Identifier (IRRID): RR2-10.1186/s13063-018-2953-4

Vaccination may prevent influenza in solid organ transplant (SOT) recipients. This study evaluates the influenza vaccine effectiveness (VE) in this high-risk population in the Netherlands. We also compared disease progression and 30-day mortality between vaccinated and unvaccinated influenza patients. In this multicenter, test-negative case-control study, SOT recipients with respiratory symptoms were included when tested for viral respiratory infections during the respiratory seasons between 1 January 2013 and 1 July 2024. Cases had a positive influenza PCR, while controls tested negative. Influenza vaccination in cases (74/174) and controls (291/602) were compared after adjusting for potential confounders. VE was calculated as (1-adjusted odds ratio) x 100. The overall VE was 6.9% (95% CI −40.9 to 38.4), with considerable variation across seasons. For those aged ≥65 years, VE was higher (32.4%, 95% CI −56.5–70.8) compared to those aged 18–64 years (4.8%, 95% CI −56.5 to 42.1). The adjusted VE against influenza A [7.5% (−46.0 to 41.3)] was higher than against influenza B (−3.8% (−146.7 to 56.3)). No differences in influenza-related complications were observed between the vaccinated and unvaccinated cases. The observed seasonal influenza vaccine effectiveness in adult SOT recipients is limited; further investigation for improvement is warranted.

The once-daily extended-release tacrolimus formulation (ER-Tac) has demonstrated similar efficacy and safety to the twice-daily immediate-release formulation (IR-Tac), but few population-based pharmacokinetic models have been developed in kidney transplant patients to optimize doses. Therefore, this study aimed i) at developing a population pharmacokinetic model for ER-Tac in adult kidney transplant patients ii) and identifying genetic factors and time-varying covariates predictive of pharmacokinetic variability to guide tacrolimus dosage during the early post-transplant period. A total of 1,067 blood tacrolimus concentrations from 138 kidney transplant patients were analyzed. A total of 29 out of 138 patients were intensively sampled for 24 h on the day 5 post-transplantation; meanwhile, for the remaining patients, concentrations were collected on days 5, 10, and 15 after transplantation. Tacrolimus daily doses and genetic and demographic characteristics were retrieved from the medical files. Biochemistry time-varying covariates were obtained on different days over the pharmacokinetic (PK) study. A simultaneous PK analysis of all concentrations was carried out using the non-linear mixed-effects approach with NONMEM 7.5. A two-compartment model with linear elimination and delayed absorption best described the tacrolimus pharmacokinetics. Between-patient variability was associated with oral blood clearance (CL/F) and the central compartment distribution volume (Vc/F). Tacrolimus concentrations standardized to a hematocrit value of 45% significantly improved the model ( < 0.001). This method outperformed the standard covariate modeling of the hematocrit-blood clearance relationship. The effect of the CYP3A5 genotype was statistically ( < 0.001) and clinically significant on CL/F. The CL/F of patients who were CYP3A5 carriers was 51% higher than that of CYP3A5 non-carriers. Age also influenced CL/F variability ( < 0.001). Specifically, CL/F declined by 0.0562 units per each increased year from the value estimated in patients who were 60 years and younger. The 36% between-patient variability in CL/F was explained by CYP3A5 genotype, age, and hematocrit. Hematocrit standardization to 45% explained the variability of tacrolimus whole-blood concentrations, and this was of utmost importance in order to better interpret whole-blood tacrolimus concentrations during therapeutic drug monitoring. The dose requirements of CYP3A5 carriers in patients aged 60 years or younger would be highest, while CYP3A5 non-carriers older than 60 years would require the lowest doses.

Background Mycoplasma hominis is a facultative anaerobic bacterium commonly present in the urogenital tract. In recent years, M. hominis has increasingly been associated with extra-urogenital tract infections, particularly in immunosuppressed patients. Detecting M. hominis in a diagnostic laboratory can be challenging due to its slow growth rate, absence of a cell wall, and the requirements of specialized media and conditions for optimal growth. Consequently, it is necessary to establish guidelines for the detection of this microorganism and to request the appropriate microbiological work-up of immunosuppressed patients. Case Presentation We hereby present two cases of solid organ transplant patients who developed M. hominis infection. Microscopic examination of the bronchial lavage and pleural fluid showed no microorganisms. However, upon inoculating the specimens onto routine microbiology media, the organism was successfully identified and confirmation was performed using 16S rDNA sequencing. Both patients received appropriate treatment resulting in the resolution of M. hominis infection. Conclusions The prompt detection of M. hominis in a clinical specimen can have a significant impact on patient care by allowing for early intervention and ultimately resulting in more favorable clinical outcomes, especially in transplant patients.