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18 pages, 801 KB  
Article
Biodegradable Polymer-Coated Surgical Sutures for Controlled and Sustained Release of Sirolimus, Tacrolimus, and Paclitaxel
by Joanna Chałupka, Karolina Piecyk, Karol Kurpiejewski and Adam Sikora
Int. J. Mol. Sci. 2026, 27(8), 3695; https://doi.org/10.3390/ijms27083695 - 21 Apr 2026
Abstract
Biodegradable polymer-coated surgical sutures represent a promising strategy for localized drug delivery to prevent post-surgical complications, such as restenosis, inflammation, and excessive tissue proliferation. In this study, bioactive coatings based on poly(L-lactic acid) (PLA), polycaprolactone (PCL), chitosan, and their binary blends were developed [...] Read more.
Biodegradable polymer-coated surgical sutures represent a promising strategy for localized drug delivery to prevent post-surgical complications, such as restenosis, inflammation, and excessive tissue proliferation. In this study, bioactive coatings based on poly(L-lactic acid) (PLA), polycaprolactone (PCL), chitosan, and their binary blends were developed and applied to PLA-based surgical sutures for controlled release of sirolimus, tacrolimus, and paclitaxel. A total of 36 coated suture formulations were prepared using solvent-based deposition techniques and systematically evaluated. In vitro drug release studies conducted under physiological conditions (PBS, 37 °C) over a 12-week period demonstrated sustained and formulation-dependent release profiles. Cumulative drug release varied significantly depending on polymer composition, ranging from 17.53% to 90.93% for sirolimus, 70.93% to 98.50% for tacrolimus, and 34.62% to 67.65% for paclitaxel. PLA-based coatings generally exhibited faster release kinetics, whereas PCL-containing formulations showed slower, more sustained release. Binary polymer blends enabled fine-tuning of release profiles, demonstrating tunable drug delivery performance. All coatings maintained structural integrity during handling and simulated suturing conditions. These findings confirm that polymer composition plays a critical role in controlling drug release kinetics and demonstrate the feasibility of biodegradable polymer-coated sutures as a versatile platform for sustained, localized drug delivery in surgical and vascular applications. Full article
15 pages, 961 KB  
Article
Minimally Invasive Therapeutic Drug Monitoring of Immunosuppressants in Children with Kidney Diseases: Validation of Fingerstick Sampling Using LC-MS/MS
by Marika Ishii, Jun Aoyagi, Natsuka Kimura, Masanori Kurosaki, Tomomi Maru, Kazuya Tanimoto, Mitsuaki Yoshino, Takane Ito, Takahiro Kanai, Hitoshi Osaka, Ryozo Nagai and Kenichi Aizawa
Pharmaceuticals 2026, 19(4), 630; https://doi.org/10.3390/ph19040630 - 16 Apr 2026
Viewed by 179
Abstract
Background/Objectives: Therapeutic drug monitoring (TDM) of immunosuppressants is essential in treating pediatric kidney diseases; however, repeated venipuncture is burdensome in children. We evaluated whether minimally invasive fingerstick capillary sampling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) provides results analytically comparable to those [...] Read more.
Background/Objectives: Therapeutic drug monitoring (TDM) of immunosuppressants is essential in treating pediatric kidney diseases; however, repeated venipuncture is burdensome in children. We evaluated whether minimally invasive fingerstick capillary sampling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) provides results analytically comparable to those of conventional venous sampling. Methods: Capillary whole blood (2.8 µL) was collected via fingersticks from pediatric patients receiving mycophenolate mofetil, with or without tacrolimus (TAC) or cyclosporine A (CsA). Drug concentrations were quantified using a previously validated simultaneous LC-MS/MS method and compared with conventional venous sampling using linear regression and Bland–Altman analyses. Results: Seventy-four paired samples from 21 patients were analyzed. Strong correlations were observed between capillary and venous samples for mycophenolic acid (MPA), TAC, and CsA (R2 > 0.90). Hematocrit correction improved agreement for MPA. Bland–Altman analyses demonstrated acceptable bias across analytes. Conclusions: Fingerstick-based microvolume sampling combined with LC-MS/MS provides analytically reliable immunosuppressant quantification in pediatric patients. Although larger clinical validation is required, this minimally invasive approach may reduce procedural burden and may support future outpatient or home-based TDM strategies. Full article
20 pages, 1234 KB  
Article
Comparing the Effectiveness of Different Tacrolimus-Containing Medications Used in Daily Patient Care of Adult Kidney Transplant Patients in Transplant Centres of Eastern Hungary in a Prospective Non-Interventional Study (DeSz Study)
by Balázs Nemes, Ákos Szeredi, Zsolt Abonyi-Tóth, Orsolya Balogh, Aranka Dimovics, Dóra Fazekas and Edit Szederkényi
Transplantology 2026, 7(2), 10; https://doi.org/10.3390/transplantology7020010 - 16 Apr 2026
Viewed by 177
Abstract
Background/Objectives: Given the narrow therapeutic range of tacrolimus and substantial inter-individual variability in trough levels, both total daily dose and the trough level-to-dose ratio are commonly used to guide dose optimization. In this study, Life-Cycle Pharma tacrolimus was compared with immediate-release tacrolimus [...] Read more.
Background/Objectives: Given the narrow therapeutic range of tacrolimus and substantial inter-individual variability in trough levels, both total daily dose and the trough level-to-dose ratio are commonly used to guide dose optimization. In this study, Life-Cycle Pharma tacrolimus was compared with immediate-release tacrolimus in a real-world setting. Methods: This longitudinal observational study included kidney transplant recipients at two Hungarian university clinics. Sixty-three (63) patients completed the study and were included in the statistical analysis. They received either Life-Cycle Pharma-tacrolimus (n = 40) or immediate-release tacrolimus (n = 23) as maintenance therapy in the two study arms, each combined with everolimus or mycophenolic acid and corticosteroids. Patients were enrolled 4–6 weeks after transplantation and prospectively followed for 48 months. Tacrolimus trough level, total daily dose and their ratio were recorded at each of the seven follow-up visits during the 48-month study period. Epidemiological data, patient characteristics, laboratory parameters (including eGFR, de novo donor-specific antibodies, and CMV and BK virus incidence), and acute rejection episodes were monitored. Results: The mean age at enrolment was 53.35 years, and 41 patients (65.08%) were male. A stable therapeutic maintenance trough level was achieved in both study arms. Life-Cycle Pharma tacrolimus required a 30% lower total daily dose than immediate-release tacrolimus to achieve comparable exposure. A gradual decline in eGFR was observed in the immediate-release tacrolimus arm (a mean decrease of 6.06 mL/min/1.73 m2 over 4 years) from a baseline level of 58.52 mL/min/1.73 m2 (±16.69), whereas GFR increased in the Life-Cycle Pharma tacrolimus arm (a mean increase of 4.76 mL/min/1.73 m2 over the same period) from a significantly lower baseline level of 46.55 mL/min/1.73 m2 (±17.04). Conclusions: Both formulations provided effective long-term maintenance immunosuppression in kidney transplant recipients and maintained stable trough levels. Life-Cycle Pharma tacrolimus represents a potential option for dose minimization, and it also helped to stabilize renal function despite the worse baseline condition. Full article
(This article belongs to the Section Solid Organ Transplantation)
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11 pages, 1337 KB  
Review
Molecular and Cellular Basis of Oral Lichen Planus: Bridging Pathogenesis and Modern Clinical Paradigms
by Kenichi Kumagai, Yuta Kishi, Taiki Suzuki, Akihisa Horie, Koji Kawaguchi and Yoshiki Hamada
Int. J. Mol. Sci. 2026, 27(8), 3444; https://doi.org/10.3390/ijms27083444 - 12 Apr 2026
Viewed by 332
Abstract
Oral lichen planus (OLP) is a chronic, T cell-mediated inflammatory disorder classified by the World Health Organization as an oral potentially malignant disorder (OPMD). Despite decades of research, its precise etiology remains incompletely understood and involves a complex interplay between genetic predisposition, environmental [...] Read more.
Oral lichen planus (OLP) is a chronic, T cell-mediated inflammatory disorder classified by the World Health Organization as an oral potentially malignant disorder (OPMD). Despite decades of research, its precise etiology remains incompletely understood and involves a complex interplay between genetic predisposition, environmental triggers, and autoimmune-like responses. This review provides a comprehensive update on OLP pathogenesis, emphasizing the role of CD8 positive cytotoxic T lymphocyte-driven basal keratinocyte apoptosis and the skewing of the T-cell receptor (TCR) repertoire. We highlight the significance of the epidermal growth factor receptor (EGFR) signaling pathway as a molecular bridge between chronic inflammation and epithelial proliferation. Furthermore, we discuss a stepwise therapeutic approach that prioritizes the management of the oral microenvironment—specifically Candida colonization and periodontal health—before escalating to immunosuppressive agents. Finally, we explore emerging precision medicine frontiers, including IL-17/IL-23 inhibitors and JAK inhibitors, alongside traditional Japanese Kampo medicine (Hange-shashin-to) and systemic adjuncts like Cepharanthine, offering a contemporary perspective on modern OLP management. This integrative framework redefines OLP not merely as a chronic inflammatory disorder, but as an immunologically sustained, microenvironment-driven, potentially malignant condition. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Oral Immunology)
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41 pages, 3002 KB  
Systematic Review
Calcineurin Inhibitors and Uric Acid Control in Solid Organ Transplantation: A Systematic Review
by Francesca K. Martino, Marco Bogo, Ludovica Brunetta, Francesca Fioretti, Leda Cattarin, Lucia F Stefanelli and Federico Nalesso
Med. Sci. 2026, 14(2), 191; https://doi.org/10.3390/medsci14020191 - 10 Apr 2026
Viewed by 328
Abstract
Background/Objectives: Asymptomatic hyperuricemia has been associated with increased cardiovascular risk; it is related to factors such as diet, genetic predisposition, and drug-related side effects. Impairment of uric acid control has been associated with the calcineurin inhibitors cyclosporin and tacrolimus, although available studies [...] Read more.
Background/Objectives: Asymptomatic hyperuricemia has been associated with increased cardiovascular risk; it is related to factors such as diet, genetic predisposition, and drug-related side effects. Impairment of uric acid control has been associated with the calcineurin inhibitors cyclosporin and tacrolimus, although available studies did not reach the same conclusions. Their widespread use in solid organ transplantation potentially exposes this population to higher cardiovascular risk. This systematic review aimed to assess their role in hyperuricemia risk compared with other immunosuppressive treatments and to clarify potential differences between cyclosporin and tacrolimus. Methods: The search was conducted in MEDLINE and Embase, limited to adult subjects, using the following terms: ((cyclosporin) OR (cyclosporine) OR (tacrolimus) OR (calcineurin inhibitor)) AND ((uric acid) OR (urate) OR (hyperuricemia)) AND ((transplant) OR (transplantation)). We assessed the quality of the studies according to the Critical Appraisal Skills Programme checklist. Results: After screening 639 manuscripts, we selected 36 studies that were relevant to our focus: 28 evaluated kidney transplant patients, while only eight focused on other solid organ transplants. Specifically, 20 studies compared calcineurin inhibitors with other immunosuppressants, while 15 assessed the impact of cyclosporin versus tacrolimus, and one study contributed to both scenarios. The prevalence of hyperuricemia ranged from 30 to 80% among patients receiving calcineurin inhibitors, with a slightly higher prevalence with cyclosporin than with tacrolimus (51–61% vs. 36–42%, respectively). The overall quality of the included studies was generally rated as low to moderate, with only ten studies focusing on uric acid control. Conclusions: Given the heterogeneity and overall quality of the available studies, no definitive conclusions can be drawn. In particular, the comparative effect of cyclosporin and tacrolimus remains uncertain because of conflicting findings across studies. Although calcineurin inhibitors may adversely affect uric acid control in transplant recipients, this association may be influenced by several confounding factors. Full article
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39 pages, 9265 KB  
Article
Innovative HPMC/PVP K90 Dissolving Microneedles Incorporating Tacrolimus-Loaded Cubosomes: A Novel Strategy for Managing Allergic Conjunctivitis
by Sammar Fathy Elhabal, Mai S. Shoela, Fatma E. Hassan, Suzan Awad AbdelGhany Morsy, Shady Allam, Reem Abd Elhameed Aldeeb, Amal Anwar Taha, Rania Mostafa Abd El Galil, Amr M. Emam, Nahla A. Elzohairy, Hanaa Wanas and Ahmed Mohsen Elsaid Hamdan
Pharmaceutics 2026, 18(4), 459; https://doi.org/10.3390/pharmaceutics18040459 - 9 Apr 2026
Viewed by 589
Abstract
Background/Objectives: Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the ocular conjunctiva. Tacrolimus (TCR), a potent calcineurin inhibitor, is limited by poor aqueous solubility and low ocular bioavailability. This study aimed to develop TCR-loaded cubosomes (TCR-Cubs) incorporated into HPMC/PVP K90 [...] Read more.
Background/Objectives: Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the ocular conjunctiva. Tacrolimus (TCR), a potent calcineurin inhibitor, is limited by poor aqueous solubility and low ocular bioavailability. This study aimed to develop TCR-loaded cubosomes (TCR-Cubs) incorporated into HPMC/PVP K90 dissolving microneedles (MNs) to enhance their therapeutic efficacy. Methods: TCR-Cubs were prepared using a modified top-down fragmentation method with glyceryl monooleate and poloxamer 407, optimized via Box–Behnken design, and incorporated into dissolving MNs. The system was evaluated in vitro, ex vivo, and in vivo using a rabbit model of allergic conjunctivitis. Results: The optimized formulation exhibited the smallest particle size (210 ± 0.91 nm), polydispersity index (0.29 ± 0.03), zeta potential (−21 ± 0.87 mV), and the highest entrapment efficiency (% 93.3 ± 0.45). The optimized formulation was incorporated into MNs via micro molding. Scanning electron microscopy (SEM) confirmed well-defined, sharp microneedles, with low height reduction (<10%) by mechanical testing and high penetration efficiency (>85–90%). In vitro release studies revealed sustained drug release of (~75–80%) over 24 h, compared to (~40%) from the TCR suspension, following diffusion-controlled kinetics. Ex vivo permeation studies showed a (~2–3-fold) enhancement in corneal drug flux. In vivo pharmacodynamic evaluation using an ovalbumin-induced allergic conjunctivitis model demonstrated significant reductions in inflammatory mediators, including inflammatory markers (TNF-α, IL-1β, IL-6, NLRP3), which were reduced by (~50–75%), with modulation of CPA3, BCL2, and TGF-β1 by qRT-PCR. Histopathology and TLR4 analysis confirmed reduced inflammation without irritation. Conclusions: This dual-delivery system offers a promising, non-invasive platform for enhanced ocular delivery of tacrolimus with superior anti-inflammatory efficacy in allergic conjunctivitis. Full article
(This article belongs to the Special Issue Non-Invasive Ocular Drug Delivery Science and Technology)
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12 pages, 2811 KB  
Case Report
Pediatric Autoimmune Sclerosing Cholangitis: Diagnostic and Therapeutic Challenges
by Raisa-Maria Sucaciu, Alina Grama, Alexandra Mititelu, Bianca Raluca Mariș, Ioana Filimon, Bobe Petrushev, Daniel Cristian Popescu, Gabriel Benţa and Tudor Lucian Pop
Pediatr. Rep. 2026, 18(2), 54; https://doi.org/10.3390/pediatric18020054 - 8 Apr 2026
Viewed by 240
Abstract
Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated [...] Read more.
Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support. Full article
(This article belongs to the Special Issue Advanced Diagnostic and Treatment Approach in Pediatric Hepatology)
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15 pages, 1226 KB  
Article
Interference of Immunosuppressive Therapies with Cellular Antimicrobial Activity Against Mycobacterium abscessus
by Sara Blanco-Conde, Miriam Retuerto-Guerrero, Ramiro López-Medrano, Cristina López-Cadenas, Santiago Vivas-Alegre, Elizabeth de Freitas-González, Nuria López-Morán and Octavio Miguel Rivero-Lezcano
Int. J. Mol. Sci. 2026, 27(7), 3230; https://doi.org/10.3390/ijms27073230 - 2 Apr 2026
Viewed by 454
Abstract
Immunosuppressive therapies increase the risk of infection, but there is little information regarding their effects on cellular antimycobacterial activity. In this context, the aim was to evaluate in vitro the impact of commonly used immunosuppressive drugs on the ability of peripheral blood mononuclear [...] Read more.
Immunosuppressive therapies increase the risk of infection, but there is little information regarding their effects on cellular antimycobacterial activity. In this context, the aim was to evaluate in vitro the impact of commonly used immunosuppressive drugs on the ability of peripheral blood mononuclear cells (PBMCs), neutrophils (polymorphonuclear cells, PMNs), and monocyte-derived macrophages (MDMs) to control Mycobacterium abscessus. Biofilm formation was assessed by quantifying bacterial colonies in cellular cultures (BCCCs) and bacterial viability by colony-forming units (CFUs). BCCCs showed significant differences among treatment conditions in PBMCs. The median (interquartile range) BCCC values for tacrolimus (TAC) 16.5 (41), everolimus (EVE) 11 (33), methotrexate (MTX) 12.5 (22) and leflunomide (LEF) 11 (29) were all significantly higher than the negative control (DMSO) 5 (14), indicating that these immunosuppressants impaired the ability of PBMCs to restrict BCCC formation. Log-transformed CFUs also varied across treatments in PMNs. Mycophenolic acid (MPA) 5.98 (2.61) and EVE 5.85 (2.77) increased LogCFU recovery compared with DMSO 5.58 (2.63), whereas MTX 5.18 (2.74) decreased it. In contrast, immunosuppressants had no significant overall effect in MDM cultures. Interestingly, 6-mercaptopurine (6MP) affected the size of colonies. Prednisolone, as expected, but also MTX and LEF, inhibited the expression in infected PBMCs of IL-1β, IL-1Ra, IL-6, CCL3, CCL5, CXCL8 and TIMP-2, whereas IL-10, CCL2 and CXCL7 expression remained essentially unchanged. Unexpectedly, methotrexate promoted CXCL8 expression, a chemokine for PMNs. These results show that commonly used immunosuppressive drugs can differentially modulate the antimycobacterial activity of PBMCs and innate immune cells, affecting both mycobacterial viability and biofilm formation. Full article
(This article belongs to the Special Issue Progression of Innate Immunity in Tuberculosis Infections)
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48 pages, 4189 KB  
Systematic Review
Analytical Models to Optimize Tacrolimus Dosing in Solid Organ Transplantation: A Systematic Review
by Elmira Amooei, Nandini Biyani, Amos Buh, Martin M. Klamrowski, Nawaf M. Alyahya, Christopher R. McCudden, James R. Green, Babak Rashidi, Haya Almuzirai, Stephanie Hoar, Ayub Akbari, Gregory L. Hundemer and Ran Klein
Pharmaceutics 2026, 18(4), 430; https://doi.org/10.3390/pharmaceutics18040430 - 31 Mar 2026
Viewed by 629
Abstract
Background: Tacrolimus dose optimization remains challenging due to its narrow therapeutic range and multiple influencing variables. This systematic review aimed to identify effective analytical modeling techniques for optimal tacrolimus dose prediction in solid organ transplant recipients. Methods: Two independent researchers conducted a comprehensive [...] Read more.
Background: Tacrolimus dose optimization remains challenging due to its narrow therapeutic range and multiple influencing variables. This systematic review aimed to identify effective analytical modeling techniques for optimal tacrolimus dose prediction in solid organ transplant recipients. Methods: Two independent researchers conducted a comprehensive review of studies examining analytical models that optimize tacrolimus dosing, searching Medline, Scopus, Embase, Web of Science, and PubMed. Results: In total, 115 studies met the inclusion criteria. Pharmacokinetic models (74 studies), particularly two-compartment with Bayesian forecasting, were most frequently used. Machine learning (ML) approaches, with increasing adoption, have demonstrated promising improved predictive accuracy. Key predictive variables included CYP3A5 genotype, hematocrit levels, post-operative days, and weight; however, the significance of genomic features seemed to diminish progressively as therapeutic drug monitoring calibrates dosing in the months following post-transplant. Only ten studies performed external validation, and none incorporated adherence data or predicted long-term graft outcomes. Conclusions: Clinical deployment of predictive models for tacrolimus dosing remains uncommon. In research, pharmacokinetic models remain prevalent, with ML approaches showing early incremental promise. Limited external validation raises generalizability concerns. Future research should prioritize outcome-based evaluation metrics rather than error metrics. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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7 pages, 19063 KB  
Case Report
Steroid-Resistant Focal Segmental Glomerulosclerosis with Alport-like Glomerular Basement Membrane Lesions Due to a MYO1E Mutation: A Pediatric Case Report
by Andrea Angioi, Doloretta Piras, Nicola Lepori, Paola Bianco, Matteo Floris, Gianfranca Cabiddu, Antonella Barreca and Antonello Pani
Int. J. Mol. Sci. 2026, 27(6), 2838; https://doi.org/10.3390/ijms27062838 - 20 Mar 2026
Viewed by 382
Abstract
Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular [...] Read more.
Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits—features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G>A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg/dL; creatinine clearance 122 mL/min) with stable sub-nephrotic proteinuria (0.52 g/day; 16 mg/m2 per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring. Full article
(This article belongs to the Special Issue Advances in Molecular Research of Kidney Diseases)
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11 pages, 705 KB  
Article
Post-Transplant Tremor: Characteristics and Differences Based on Sex and Post-Transplant Therapy
by Srdjana Telarovic, Maja Vrdoljak Pazur, Nikolina Zupancic, Anamarija Strajduhar and Irma Telarovic
Neurol. Int. 2026, 18(3), 56; https://doi.org/10.3390/neurolint18030056 - 17 Mar 2026
Viewed by 446
Abstract
Background/Objectives: Kidney transplantation is the standard of care for the majority of patients with end-stage kidney disease. Neurological complications are common, and among them, tremor is very frequent and usually attributed to immunosuppressive drug toxicity. Methods: In this retrospective study, we [...] Read more.
Background/Objectives: Kidney transplantation is the standard of care for the majority of patients with end-stage kidney disease. Neurological complications are common, and among them, tremor is very frequent and usually attributed to immunosuppressive drug toxicity. Methods: In this retrospective study, we investigate the incidence and characteristics of tremor in kidney transplant patients and analyze its occurrence with respect to a multitude of demographic and clinical parameters, thereby aiming to confirm the role of calcineurin inhibitor-induced neurotoxicity and to identify other putative predictive factors. Furthermore, we characterize post-transplant tremor with the goal of identifying its clinical features and determining the impact on quality of life. Results: A total of 129 kidney transplant recipients were screened; six patients were excluded due to a history of movement disorders prior to kidney transplantation. In total, 123 patients were included in the final analysis—69 male (56%) and 54 female patients (44%), with a median age of 50. A total of 36% (46 patients) developed tremor in the post-transplant period. Using both univariable and multivariable analyses, we found that female sex and tacrolimus use were independently associated with the development of post-transplant tremor. In addition, multivariable analysis identified an association between younger age and post-transplant tremor. Furthermore, we observed a trend in the duration of symptoms in relation to the calcineurin inhibitor choice. Conclusions: Despite a relatively high prevalence (36%), post-transplant tremor does not significantly impact the QoL and spontaneously resolves within 1 year in adult kidney transplant recipients. Female sex and tacrolimus were identified as independent predictors of post-transplant tremor in renal transplant recipients. Full article
(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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9 pages, 1620 KB  
Systematic Review
Annular Lichen Planus of the Penis Successfully Treated with Topical Tacrolimus 0.1% Ointment: A Case Report and Systematic Review of the Literature
by Andrea D’Arino, Maria Concetta Fargnoli, Francesca Di Tullio, Carlo Cota, Paola Pasquini, Pasquale Frascione and Victor Desmond Mandel
Life 2026, 16(3), 482; https://doi.org/10.3390/life16030482 - 16 Mar 2026
Viewed by 603
Abstract
Introduction: Annular Lichen Planus (ALP) of the penis is a rare variant of genital lichen planus. Clinically, it is characterized by violaceous plaques with an annular configuration and central clearing. The diagnosis can be challenging, especially considering its rarity, and histopathological confirmation is [...] Read more.
Introduction: Annular Lichen Planus (ALP) of the penis is a rare variant of genital lichen planus. Clinically, it is characterized by violaceous plaques with an annular configuration and central clearing. The diagnosis can be challenging, especially considering its rarity, and histopathological confirmation is often necessary to differentiate it from other annular dermatoses. Methods: We report a rare case of genital ALP in a male patient, while reviewing previously reported cases to provide a comprehensive overview of this rare condition. Results: A 63-year-old white male was referred to our outpatient department presenting with symptomatic annular erythematous-violaceous lesions on the glans penis. A diagnosis of genital ALP was clinically suspected and subsequently confirmed by histopathology. The patient was started on topical tacrolimus 0.1% ointment twice daily, achieving a complete clinical resolution after 6 consecutive weeks of treatment. No signs of local recurrence were observed after a one-year follow-up. We carried out a systematic review of the literature which identified a limited number of similar cases. Conclusions: This review underscores the importance of clinical suspicion and biopsy for accurate diagnosis and effective management of penile ALP. Topical tacrolimus 0.1% ointment is a safe and effective treatment for penile ALP and can be used as an alternative of corticosteroids. Full article
(This article belongs to the Special Issue Skin Diseases and Dermatologic Comorbidities)
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18 pages, 630 KB  
Article
Early Post-Transplant Changes in Lipoprotein(a), Autotaxin Activity, and Lipid Profile: A Prospective Observational Study of Tacrolimus-Treated Kidney Transplant Recipients in Poland
by Beata Bzoma, Agnieszka Kuchta, Magdalena Dzwonkowska, Daria Kazimierska, Maciej Jankowski and Alicja Dębska-Ślizień
Int. J. Mol. Sci. 2026, 27(6), 2641; https://doi.org/10.3390/ijms27062641 - 13 Mar 2026
Viewed by 387
Abstract
Kidney transplantation (KTx) corrects many uremia-related metabolic disturbances; however, dyslipidemia remains common in kidney transplant recipients and contributes to persistent cardiovascular risk. Lipoprotein(a) [Lp(a)] is a largely genetically determined proatherogenic lipoprotein that increases in advanced chronic kidney disease (CKD) and may decrease after [...] Read more.
Kidney transplantation (KTx) corrects many uremia-related metabolic disturbances; however, dyslipidemia remains common in kidney transplant recipients and contributes to persistent cardiovascular risk. Lipoprotein(a) [Lp(a)] is a largely genetically determined proatherogenic lipoprotein that increases in advanced chronic kidney disease (CKD) and may decrease after restoration of renal function. Autotaxin (ATX), an enzyme involved in proinflammatory lipid signaling through the ATX–lysophosphatidic acid axis, has also been implicated in cardiovascular pathology, but its early post-transplant dynamics remain poorly characterized. In addition to quantitative lipid abnormalities, CKD is associated with high-density lipoprotein (HDL) dysfunction and reduced paraoxonase-1 (PON-1) activity; however, data on early post-transplant changes in PON-1 activity are limited. In this prospective observational study, lipid profile parameters, Lp(a) concentration, ATX activity, and PON-1 activity were assessed in 55 Caucasian patients with CKD stage 5, most of whom were dialysis-dependent, before and 2–3 weeks after KTx. All recipients received tacrolimus-based maintenance immunosuppression with corticosteroids and mycophenolate mofetil. After KTx, Lp(a) levels decreased by a median of 21% and ATX activity by 28% (both p < 0.001). Lp(a) and ATX showed no cross-sectional or longitudinal association either before or after transplantation, and their percentage changes were not correlated. In contrast, conventional lipid fractions increased significantly, including total cholesterol (+22%), LDL cholesterol (+27%), HDL cholesterol (+24%), and triglycerides (+55%) (all p < 0.001). PON-1 activity increased by approximately 13% after KTx (p < 0.001), and its percentage change correlated positively with the increase in HDL cholesterol. In exploratory analyses, the magnitude of Lp(a) reduction was associated with early graft function: patients with eGFR <45 mL/min/1.73 m2 exhibited a significantly smaller decline in Lp(a) than those with better graft function (−4.8% vs. −26.7%, p = 0.009). Multivariable analysis showed that demographic characteristics, body mass index, tacrolimus exposure, and post-transplant eGFR did not independently predict the magnitude of Lp(a) reduction. Tacrolimus trough concentrations and cumulative corticosteroid exposure were not associated with lipid parameters or their changes, except for a single subgroup difference in PON-1 activity of uncertain clinical significance. In summary, in the early period after KTx under tacrolimus-based immunosuppression, Lp(a) concentration and ATX activity decrease, whereas conventional lipid fractions increase and PON-1 activity improves. These changes were not associated with tacrolimus exposure or cumulative corticosteroid dose. The reduction in Lp(a) was associated with early graft function in exploratory analyses, suggesting that recovery of renal function may contribute to early post-transplant Lp(a) dynamics; however, no independent causal relationship was established, and the findings should be interpreted cautiously given the limited sample size and exploratory design. The clinical significance of these changes for long-term cardiovascular and graft outcomes requires further investigation. Full article
(This article belongs to the Special Issue Molecular Research on Kidney Disease/Renal Dysfunction)
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19 pages, 702 KB  
Review
Pediatric Vernal Keratoconjunctivitis (VKC): Current State and Future Directions—A Narrative Review of Clinical Features, Diagnostic Strategies, and Emerging Therapies
by Elia Pignataro, Giulia Brindisi, Alessandra Gori, Giorgio Colletti, Paola Moraca, Bianca Laura Cinicola, Alberto Spalice, Caterina Anania and Anna Maria Zicari
Children 2026, 13(3), 335; https://doi.org/10.3390/children13030335 - 26 Feb 2026
Viewed by 626
Abstract
Vernal keratoconjunctivitis (VKC) represents far more than a typical allergic eye disease. It is a distinct and often underestimated chronic inflammatory condition that primarily affects children during critical stages of physical and emotional development. Though frequently grouped with seasonal allergic conjunctivitis, VKC differs [...] Read more.
Vernal keratoconjunctivitis (VKC) represents far more than a typical allergic eye disease. It is a distinct and often underestimated chronic inflammatory condition that primarily affects children during critical stages of physical and emotional development. Though frequently grouped with seasonal allergic conjunctivitis, VKC differs significantly in its immunopathology, clinical presentation, and long-term implications. Its intense ocular symptoms and its potential for corneal damage and substantial psychosocial burden require, rather than symptom control, coordinated and multidisciplinary management. This narrative review explores VKC from every angle, with a particular focus on its implications for pediatric care. VKC, in fact, represents a genuine clinical challenge: as its symptoms can mimic milder forms of conjunctivitis, its course is often unpredictable, and its treatment requires balancing efficacy and safety in vulnerable age groups. We examined the immunological mechanisms that make it a model of localized Th2 inflammation, the diagnostic pitfalls that delay recognition, and the evolving treatment landscape, from conventional therapies like cyclosporine A and tacrolimus to innovative agents such as omalizumab and dupilumab. We also highlighted the role of emerging biomarkers, the influence of environmental and microbiome factors, and the urgent need for standardized care pathways. As research continues to expand our understanding, VKC is emerging as a prime example of how personalized medicine and translational science can intersect to address complex immune-mediated diseases in children. For the ones treating pediatric allergic disorders, VKC is no longer a rare curiosity: it is a clinical challenge worth understanding deeply. Full article
(This article belongs to the Section Pediatric Allergy and Immunology)
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15 pages, 406 KB  
Article
Recurrence and Outcomes of Lupus Nephritis After Renal Transplantation: Analysis of Nine Cases and Review of the Literature
by Magdalena Morytko, Radosław Dziedzic, Weronika Pociej-Marciak, Mariusz Korkosz and Joanna Kosałka-Węgiel
J. Clin. Med. 2026, 15(5), 1682; https://doi.org/10.3390/jcm15051682 - 24 Feb 2026
Viewed by 503
Abstract
Background and Objectives: Recurrence of lupus nephritis (LN) after kidney transplantation is a major clinical concern in patients with systemic lupus erythematosus (SLE) who progress to end-stage renal disease (ESRD). Reported rates of post-transplant LN recurrence vary widely and are influenced by patient [...] Read more.
Background and Objectives: Recurrence of lupus nephritis (LN) after kidney transplantation is a major clinical concern in patients with systemic lupus erythematosus (SLE) who progress to end-stage renal disease (ESRD). Reported rates of post-transplant LN recurrence vary widely and are influenced by patient characteristics, immunosuppressive regimens, and indications for allograft biopsy. Patients and Methods: Medical records of adult LN patients treated at the University Hospital in Kraków, Poland, during the years 2012–2022 were retrospectively reviewed to identify individuals who progressed to ESRD and received a kidney transplant. Data collected included patient demographics as well as clinical, laboratory, transplant-related, and dialysis-related information. Results: Among 1039 patients with SLE, LN was diagnosed in 351 (33.8%), and 28 (8.0%) progressed to ESRD, of whom n = 9 (32.1%) underwent kidney transplantation. All patients received deceased-donor grafts, with a median time from ESRD to transplantation of 3 years (range 1–8) and a median post-transplant follow-up of 6 years (3–20). Maintenance immunosuppression consisted predominantly of glucocorticosteroids, mycophenolate mofetil, and tacrolimus in 77.8% of patients, with basiliximab induction was used in 2 of 2 patients with available data. Biopsy-proven LN recurrence occurred in 22.2% (2/9) of recipients. Graft loss was observed in 22.2% (2/9), while overall mortality reached 33.3% (3/9), including one peri-transplant death and one death due to infectious complications. Hematological manifestations were present in 100% of patients, hypercholesterolemia in 100%, and arterial hypertension in 88.9%, while anti-dsDNA antibodies were detected in 77.8%. LN relapse occurred despite standard immunosuppressive therapy and in the absence of consistent clinical or immunological predictors. Conclusions: LN recurrence occurred in 2 of 9 patients (22.2%). Patients with LN after kidney transplantation require careful long-term monitoring and individualized immunosuppressive management, considering baseline risk profile and relevant clinical with immunological factors. Full article
(This article belongs to the Section Immunology & Rheumatology)
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