Search Results (1,764)

Background/Objectives: Prostate cancer is one of the most common non-skin solid malignancies among male solid organ transplant recipients (SOTRs), in whom radical prostatectomy is technically demanding. We report the first use of indocyanine green (ICG) fluorescence for simultaneous transplanted-ureter identification and renal graft vascular mapping during robot-assisted radical prostatectomy (RARP), and the first use of the CMR Versius^® platform in a SOTR. Methods: Retrospective case series of four consecutive male SOTRs (two renal [RTRs], two hepatic) undergoing RARP. In both RTRs, a dual-route ICG protocol was used on the da Vinci Xi with Firefly^® imaging: pre-docking intraureteral ICG via a ureteral catheter for ureter identification, plus an intravenous ICG bolus for graft vascular mapping and cortical perfusion. One hepatic recipient was operated with the CMR Versius^® system using an infra-umbilical port configuration to avoid the chevron transplant scar. Results: All four procedures were completed robotically without conversion. Median operative time was 176 min and median estimated blood loss 350 mL. Surgical margins were negative (R0) in all four; final pathology was pT3aN0 in three and pT2N0 in one, although in the renal recipients nodal staging reflected a contralateral-only dissection. PSA was undetectable at three months in all patients. One hepatic recipient later developed biochemical recurrence, managed with salvage radiotherapy and androgen deprivation therapy, with subsequent undetectable PSA. One hepatic recipient had a Clavien–Dindo IIIa complication. No graft dysfunction occurred. Conclusions: ICG-guided RARP and the CMR Versius^® platform appear technically feasible in carefully selected solid organ transplant recipients treated at an experienced multidisciplinary centre, with no graft-related complications observed in this small initial series. These preliminary findings require validation in larger, multicenter studies before general safety and oncological efficacy can be established. Full article

Background/Objectives: Carbapenem-resistant Gram-negative (CR-GN) infections are associated with high mortality in intensive care units (ICUs), with limited therapeutic options. We aimed to evaluate microbiological and clinical outcomes associated with cefiderocol in critically ill patients with multidrug-resistant (MDR) Gram-negative infections. Methods: This retrospective, single-center case series included 25 critically ill patients with carbapenem-resistant or multidrug-resistant Gram-negative infections treated with cefiderocol between May 2024 and October 2025 in a mixed ICU of a tertiary hospital in Romania. Microbiological cure was defined as eradication of the designated target pathogen at the end of therapy. Clinical evolution was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, as well as inflammatory biomarkers including white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Results: Klebsiella pneumoniae was the predominant pathogen, identified in 23 of 25 patients (92%), followed by Acinetobacter baumannii (11/25, 44%) and Pseudomonas aeruginosa (6/25, 24%). As multiple pathogens were co-isolated in 16 patients (64%), percentages exceed 100% and are reported as proportions of patients rather than of total isolates. Microbiological cure was achieved in 68% of patients. Mortality was markedly higher in patients without microbiological eradication (88% vs. 35%). Higher baseline APACHE II (HR 1.18, 95% CI 1.02–1.37) and SOFA scores (HR 1.33, 95% CI 1.07–1.65) were associated with increased mortality. Early initiation of cefiderocol (≤10 days from ICU admission) was associated with improved microbiological and clinical outcomes compared to delayed treatment. Reductions in severity scores and inflammatory markers, including C-reactive protein (CRP) and procalcitonin (PCT), were observed during therapy. Pathogen type and combination therapy were not clearly associated with outcomes in this cohort. Conclusions: Cefiderocol was observed in association with clinically relevant rates of microbiological eradication and improvements in clinical parameters in critically ill patients with MDR Gram-negative infections. Outcomes appeared to be primarily determined by baseline disease severity, while earlier initiation of therapy was associated with more favourable microbiological and clinical outcomes, although causality cannot be established given the observational design and absence of a comparator group. These findings are hypothesis-generating and supportive of a potential role for cefiderocol as a salvage option in high-risk ICU populations, pending validation in larger, prospective, controlled studies. Full article

KRAS G12C, long considered an undruggable oncogenic driver, has become one of the most consequential therapeutic targets in non-small cell lung cancer (NSCLC). The discovery of a cryptic binding pocket accessible in the GDP-bound state enabled covalent inhibitors—sotorasib and adagrasib—that have received regulatory approval for previously treated KRAS G12C-mutant NSCLC, with sotorasib demonstrating PFS and OS superiority over docetaxel in CodeBreaK 200 and adagrasib showing meaningful intracranial activity and a progression-free survival benefit over docetaxel in KRYSTAL-12. Yet response durability is limited by on-target switch-II pocket mutations, upstream RTK and SHP2-mediated bypass signaling, downstream MAPK and PI3K-AKT reactivation, phenotypic plasticity, and adverse modulation by co-occurring STK11, KEAP1, and TP53 alterations. Next-generation covalent inhibitors (divarasib, glecirasib, olomorasib), tri-complex RAS(ON) inhibitors (RMC-6291), pan-KRAS agents, and rationally designed combinations with EGFR, SHP2, SOS1, and PD-1 inhibitors are repositioning KRAS-directed therapy toward earlier lines of treatment. This review integrates the structural, signaling, and clinical biology of KRAS G12C with contemporary trial and real-world evidence to examine the emerging case for first-line KRAS G12C inhibition in genomically defined subsets of NSCLC. First-line use nonetheless remains investigational; platinum-based chemoimmunotherapy remains the standard of care outside of clinical trials, and a frontline indication will require confirmation from randomized phase III trials. Full article

Background. When free margins can be achieved and adjacent joints can be preserved, limb salvage surgery is the preferred treatment for intercalary paediatric bone tumours in the lower extremity. Biological reconstruction techniques include allograft, free vascularised fibular graft (FVFG), and allograft combined with FVGF (Capanna technique). This review summarises current evidence on outcomes and complications, and proposes directions for future research to refine patient selection. Methods. A systematic review was conducted using PubMed, Scopus, Embase, and Cochrane Library. Eligible studies reported outcomes of allograft, FVFG, or combined techniques for intercalary lower limb reconstruction in children or adolescents. Results. Twenty-five articles met the inclusion criteria (8 allograft, 7 FVFG, 14 Capanna); four studies reported two techniques. In total, 391 patients were included (allograft 147, FVFG 51, Capanna 193). Mean defect lengths were 14.9 cm (allograft), 14.5 cm (FVFG), and 14.7 cm (Capanna). Time to union was 8.5 months for allografts, 11.4 for Capanna, and 12.5 for FVFG. Non-union occurred in 14.7%, 13.2%, and 10.3%, and delayed union in 13.6%, 4.8%, and 7.9% for FVFG, allograft, and Capanna, respectively. Fractures were 40.5% for FVFG, 18.4% for allograft, and 23.5% for Capanna. Infections were least common with FVFG (2.7%). Conclusions. The reconstruction strategy should be tailored to anatomical location, defect size, and patient-specific factors. Although infections rates were lowest with FVFG, time to union was longer and the postoperative fracture rate was higher compared to the allograft or Capanna technique. Allografts demonstrated the shortest time to union and lowest fracture risk. The Capanna technique may be beneficial when factors including chemotherapy, poor host bone quality, or high mechanical load are present, but comes at a cost of morbidity and complexity. Full article

Background: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is an established salvage therapy for relapsed or refractory (R/R) germ cell tumors (GCTs). Methods: We conducted a retrospective analysis of 9 patients (23–41 years of age) with relapsed/refractory (R/R) GCTs treated according to the Swedish–Norwegian Testicular Cancer Group Clinical Protocol (SWENOTECA), at the Specialized Hospital for Active Treatment of Hematological Diseases (SHATHD) in Sofia, Bulgaria. The study evaluates the efficacy and safety of HDCT followed by ASCT in R/R GCTs eligible for second-line consolidation. The cohort was predominantly high-risk, with 77.7% of patients exhibiting stable or progressive disease (SD/PD) after first-line platinum therapy. Response was assessed via RECIST 1.1 criteria and tumor marker monitoring. Results: Median OS and PFS were 8.4 and 5.9 months, respectively. While the ORR post-ASCT was 33.3% (all CR), the 2-year survival plateau (33.3%) suggests curative potential in a subset of patients. Notably, there was no treatment-related mortality (TRM). Conclusions: Tandem HDCT is a feasible salvage strategy with manageable toxicity and no TRM in this small, heavily pre-treated cohort. Although efficacy results are exploratory due to the limited number of patients, the observed long-term remissions confirm the curative potential of this standard-of-care consolidation in a real-world clinical setting. Full article

Background: Soft tissue sarcomas (STS) in children, adolescents, and young adults are rare and biologically heterogeneous, and prognostic factors for local recurrence, metastasis, and survival remain incompletely defined. This study aimed to characterize oncological outcomes and to explore clinical, surgical, and treatment-related factors associated with these endpoints at a tertiary sarcoma center. Methods: This retrospective single-center cohort study included 42 consecutive patients aged ≤25 years with histologically confirmed STS who underwent definitive surgery between June 2018 and November 2025. Local recurrence-free (LRFS), metastasis-free (MFS), event-free (EFS), and overall survival (OS) were estimated by the Kaplan–Meier method with competing-risks sensitivity analyses. Given the limited number of events, pre-specified univariable comparisons (log-rank, Fisher exact, Mann–Whitney U) were performed and regarded as exploratory. Results: The median age was 16.7 years and 26 patients (61.9%) were female. A microscopically complete (R0) resection was achieved in 35 of 41 patients with assessable margins (85.4%), and limb preservation in 38 (90.5%). Over a median follow-up of 23.1 months, the 24- and 60-month estimates were LRFS 85.7% and 79.6%, MFS 93.3% and 84.8%, EFS 82.3% and 64.7%, and OS 96.0% and 81.5%, respectively. Metastatic disease at diagnosis was the only variable associated with metastatic status at last follow-up (p = 0.035). No factor was robustly associated with local recurrence; anatomical site (p = 0.68), resection-margin status (p = 0.23), and tumor volume (p = 0.97) were not significant, and an apparent association with a sub-millimeter margin rested on a single event (complete separation). Conclusions: Metastatic disease at diagnosis emerged as the most important prognostic factor for MFS in our cohort. Despite the complexity of treatment in this young patient population, high rates of complete resection and limb preservation were achieved, highlighting the value of multidisciplinary management in specialized sarcoma centers. While the limited cohort size did not allow the identification of further statistically significant prognostic factors for local recurrence, such associations may become detectable in larger multicenter studies. Full article

Distinguishing tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) remains difficult when presentation is non-specific, blood cultures are negative, or initial biopsy is non-diagnostic. The two entities differ substantially in antimicrobial strategies, resistance testing requirements, public health interventions, and surgical thresholds, yet diagnostic delay is associated with neurological deficits, spinal instability, and permanent deformity. This narrative review maps the non-imaging evidence most useful for frontline differentiation between TS and PS across five domains: epidemiology and risk stratification, clinical presentation, laboratory markers, tissue acquisition and histopathology, and molecular diagnostics. PubMed/MEDLINE was searched from inception to 31 March 2026 using pre-specified Boolean search terms; a secondary Scopus search identified no additional eligible records. Following screening, approximately 90 records were included in this synthesis. Priority was given to comparative TS-versus-PS cohorts, biopsy-yield and culture-negative studies, pathology series, pediatric data, and recent molecular diagnostics literature. Epidemiological TB (tuberculosis) risk, longer symptom duration, constitutional symptoms, deformity, and a less intense acute-phase response increase the probability of TS, whereas healthcare exposure, bacteraemia, recent spinal procedures, and brisk neutrophilic inflammation favor PS. In stable patients, the highest-yield strategy is early blood cultures followed by image-guided biopsy with parallel tissue allocation for bacterial culture, mycobacterial studies, histopathology, and selected molecular assays. No single laboratory marker reliably distinguishes TS from PS without tissue confirmation. Per a 2023 systematic review and meta-analysis, image-guided percutaneous biopsy achieves microbiological confirmation in approximately one-third of cases. Histopathology demonstrating caseating granulomatous inflammation supports TS, although a substantial minority of confirmed cases lack classic features. Supported by cohort prospective data, Xpert MTB/RIF Ultra has the clearest first-line molecular role when TS is plausible and should be requested at the time of first biopsy rather than reserved for salvage testing; broader or targeted next-generation sequencing is best reserved for selected unresolved cases. Imaging differentiation is addressed in the companion manuscript, Part II. Full article

Background: Multidrug-resistant Gram-negative infections remain a major challenge in critically ill patients, particularly when caused by carbapenem-resistant pathogens with limited therapeutic options. Although eravacycline has emerged as a potential salvage agent, real-world data in high-acuity intensive care populations remain scarce. Methods: We conducted a retrospective cohort study including adult ICU patients who received eravacycline as salvage therapy for multidrug-resistant Gram-negative infections between February 2024 and September 2025 in a tertiary-care center. Demographic, clinical, microbiological, and treatment-related variables were extracted from electronic records. Infection complexity was classified as monomicrobial single-site, monomicrobial multi-site, or polymicrobial. The primary outcome was in-hospital mortality; secondary outcomes included clinical response, microbiological eradication, and safety. Results: Forty critically ill patients were included (median age 58 years, IQR 47–69; mean APACHE II 16.4 ± 6.9; mean SOFA 5.5 ± 3.3). Pulmonary (62.5%) and intra-abdominal (55.0%) infections were most frequent. Klebsiella pneumoniae predominated (75.0%), followed by Acinetobacter baumannii (35.0%) and Pseudomonas aeruginosa (22.5%). Most patients received combination antimicrobial therapy. Microbiological eradication or presumed eradication was documented in 24 patients (60.0%), yet overall in-hospital mortality remained high (75.0%). Baseline disease severity and persistent inflammatory response were more strongly associated with unfavorable outcomes than treatment timing or duration. Conclusions: In this real-world ICU cohort, eravacycline-based salvage therapy was associated with moderate microbiological response but very high mortality, reflecting the severity of underlying critical illness. The dissociation between microbiological eradication and survival suggests that outcomes are more closely related to host factors and unresolved systemic inflammation than to pathogen clearance alone. Eravacycline remains one of the few agents active against MDR Gram-negative pathogens (with no activity against Pseudomonas aeruginosa), frequently used off-label; larger controlled studies are needed to establish efficacy beyond complicated intra-abdominal infections. Full article

Off-grid residential microgrids in tropical regions require storage architectures capable of maintaining renewable electricity supply under variable solar resources, evening demand peaks, and diverse household consumption levels. In PV–battery–hydrogen systems, however, economic indicators can be difficult to interpret when software-reported costs are compared directly with externally calculated LCOE values based on different accounting conventions. This study presents a metric-reconciled techno-economic reconstruction approach for retained PV–battery–hydrogen microgrid configurations serving off-grid residential demand in Chetumal, Mexico. The objective is not to introduce a new global optimization or to claim the universal superiority of a specific architecture, but to separate archived HOMER Pro benchmark outputs from an external techno-economic model (TEM). The TEM reconstructs net present cost, scheduled replacements, salvage treatment, discounted delivered electricity, HOMER-derived LCOE, TEM-derived LCOE, sensitivity indicators, and storage role metrics using declared accounting assumptions. The approach is applied to two representative residential demand scenarios of 16.67 and 53.42 kWh/day. Both retained configurations achieved a 100% renewable fraction with negligible unmet load. Battery discharge increased from 827.12 kWh/year in the low-demand case to 6125.52 kWh/year in the high-demand case, highlighting the increasing role of the battery in short-duration balancing. In contrast, the hydrogen pathway acted as a delayed-backup layer by converting surplus PV electricity into hydrogen and later recovering it through PEM fuel cell generation. The TEM closely matched the HOMER-derived LCOE benchmark, with deviations below 4%, yielding TEM-derived LCOE values of 0.3320 and 0.3571 USD/kWh for the low- and high-demand cases, respectively. Sensitivity analysis showed that delivered electricity, discount rate, PV cost, and battery cost were the main LCOE drivers, while deterministic multi-parameter scenarios confirmed the combined influence of financing, component costs, O&M, PV degradation, and electricity delivered. Overall, the proposed approach provides an auditable basis for metric reconciliation, early-stage technology assessment, and storage role interpretation in tropical off-grid microgrids. Future extensions should include architecture-level re-optimization, flexible loads, degradation-aware modeling, and part-load component behavior. Full article

Kienböck disease, osteonecrosis of the lunate of uncertain aetiology, presents with progressive pain, stiffness, and grip loss in dominant-hand-using adults during their most productive working years, yet its rehabilitation literature has lagged behind its surgical counterpart. This narrative review synthesises current rehabilitation evidence across conservative and post-operative pathways, mapping recommendations to disease stage and to surgical procedure. Following SANRA-aligned methods with selected PRISMA 2020 transparency elements, we appraise immobilisation and orthotic management, dart-throwing-motion-plane mobilisation, sensorimotor retraining, oedema and pain control, psychosocial screening, and procedure-specific protocols that span joint-levelling osteotomy, vascularised bone grafting (including medial femoral trochlea flap), limited intercarpal arthrodeses, proximal row carpectomy, wrist denervation, and salvage arthrodesis or arthroplasty. Patient-reported, performance-based, and occupational outcome instruments are reviewed, with explicit declaration that no Kienböck-validated MCIDs exist. We also set out an integrative reference frame that cross-walks osseous, articular, and tissue-healing axes, offered as clinical orientation rather than as a validated algorithm. The most pressing evidence gaps (Kienböck-specific functional movement screens, sustained return-to-work data, and procedure-specific rehabilitation cohorts) are translated into four registered, powered, COMET-aligned trial proposals. Full article

Pyridoxal 5′-phosphate (PLP), the catalytically active form of vitamin B6, is an enabling cofactor for synthetic biocatalysis, but PLP production remains difficult to compare across chemical, microbial, and cell-free routes. This review reframes PLP synthesis as a biocatalytic cascade-design problem. Chemical phosphorylation is used as a benchmark for selectivity, reagent burden, and purification, whereas de novo and salvage-pathway enzymes define the molecular constraints governing biological production. We focus on PdxK/PdxY, PdxH/PNPOx, PdxS/PdxT, engineered acid phosphatase, and polyphosphate kinase modules. Recent PPi-driven and PPK/polyP-supported cascades show that high PLP concentrations are attainable, but titer alone is not sufficient for route comparison: substrate identity, phosphate-donor equivalents, adenylate loading, whole-cell or cell-free format, oxygen and H₂O₂ management, catalyst reuse, salt burden, isolated recovery, and product purity must be evaluated separately. By distinguishing PN fermentation, intracellular cofactor supply, PNP intermediates, reaction-broth PLP concentration, and isolated PLP yield, this review proposes a route-readiness map for PLP-producing cascades. The most promising next-generation systems will couple product-tolerant phosphorylation, oxidase performance, cofactor regeneration, and downstream stabilization in a single process-aware design. Full article

Acute myeloid leukaemia (AML) exhibits profound metabolic plasticity that enables leukaemic cells to survive environmental stress, nutrient limitation, and therapeutic pressure, ultimately driving disease persistence and relapse. While genetic and epigenetic alterations have guided risk stratification and therapeutic development, accumulating evidence indicates that nutrient-dependent metabolic rewiring represents a critical and targetable vulnerability in AML. Nicotinamide adenine dinucleotide (NAD) is a central metabolic cofactor whose intracellular availability is tightly linked to dietary intake of its precursors, including tryptophan, niacin (vitamin B3), nicotinamide, and nicotinamide riboside. NAD supports redox balance, mitochondrial metabolism, DNA repair, and stress adaptation, processes that are particularly critical for leukaemic stem cell survival under therapeutic stress. Recent studies demonstrate that AML cells, including those resistant to venetoclax- and hypomethylating agent–based regimens, exhibit heightened dependence on the NAD salvage pathway mediated by nicotinamide phosphoribosyltransferase (NAMPT). Pharmacological inhibition of this pathway induces profound NAD depletion, mitochondrial dysfunction, and selective leukaemic cell death. In this review, we integrate nutritional biology with emerging translational evidence to examine NAD metabolism as a nutrient-regulated metabolic vulnerability in AML. We discuss dietary sources and systemic regulation of NAD, the role of NAD-dependent pathways in leukaemic persistence, the translational exploitation of NAD salvage dependency, and the emerging controversy surrounding NAD supplementation in cancer. Finally, we highlight key knowledge gaps and future directions at the interface of nutrition, metabolism, and therapy response in AML. Full article

Background: Endovascular repair with covered stent is an established minimally invasive treatment for popliteal artery lesions, particularly in elderly or high-risk patients. Infectious complications are exceptionally rare but may result in arterial destruction, limb loss, and death. Salmonella species demonstrate a well-recognized affinity for diseased arterial walls and prosthetic vascular material. Case Presentation: An 82-year-old man with stage G4 chronic kidney disease and previous nephrectomy for renal cell carcinoma, complicated by Salmonella Enteritidis septic shock 20 years earlier, presented with acute left lower limb ischemia caused by a post-traumatic popliteal artery pseudoaneurysm. Urgent endovascular repair was performed using a 6 × 100 mm covered stent (Viabahn) with adjunctive angioplasty of the anterior tibial artery. Two weeks later, he was readmitted with fever, severe popliteal pain, local erythema, and elevated inflammatory markers. Imaging demonstrated early stent occlusion with a large peri-graft abscess and contained arterial rupture. Emergency open conversion included radical debridement, complete graft explantation, and popliteal-to-posterior tibial bypass using an autologous great saphenous vein. Cultures grew Salmonella Enteritidis. Retrospective history revealed a previously undocumented episode of Salmonella Enteritidis bacteremia approximately 20 years earlier. At 2-year follow-up, the patient remained free of recurrent infection with a patent vein graft and preserved ambulatory function. Conclusions: Early Salmonella Enteritidis infection of a popliteal covered stent is an exceptionally rare but life-threatening complication. This case suggests that remote Salmonella bacteremia may represent a potential, hypothesis-generating risk factor for prosthetic graft infection. Prompt graft explantation followed by radical debridement and autologous venous reconstruction remain essential for durable limb salvage. Full article

Periodic resource reservation underpins vehicular sidelink traffic, yet its compatibility is inherently asymmetric. In New Radio (NR) sidelink Mode 1, two configured grant (CG) streams collide if and only if the greatest common divisor (GCD) of their periods divides their offset difference, so coprime periods cannot be separated by any offset on a single subchannel. Admission opportunity is thus governed by the arithmetic of the period set, not by load alone—a disparity we call schedulability asymmetry. We propose Divisor-Aligned Period Decomposition (DAPD), which fixes a common divisor d and reduces coexistence to a closed-form GCD test: periods that are multiples of d are admitted directly, and incompatible ones are reshaped into a d-aligned substitute within the delay budget rather than rejected. This levels the schedulability asymmetry at its source for any catalog period whose delay budget admits a d-compatible substitute: once every request is represented on a common divisor, no period is structurally disadvantaged, so such a period can be admitted regardless of its arithmetic relationship to the others. Under a collision-only scheduler model that isolates deterministic reservation collisions from physical-layer effects, every admitted CG is collision-free by construction. An extension, DAPD+, salvages the resulting slack with dynamic grants that never overlap an admitted CG. In simulation over 1000 seeds across vehicle densities up to subchannel saturation, DAPD+ attains the highest overall packet delivery ratio among all evaluated schedulers, including an oracle offset optimizer and a recent multi-configuration CG scheduler, while holding admitted-CG delivery at one and keeping far more per-vehicle delivery ratios above target, where the reactive baseline’s per-vehicle reliability collapses with density. DAPD+ thus serves the largest volume of periodic traffic at high reliability without sacrificing aggregate throughput, equalizing admission opportunity across heterogeneous periods. Full article

Natural killer cell large granular lymphocytic leukemia (NK-LGLL) is a rare and heterogenous lymphoproliferative disorder. This study retrospectively evaluated 35 consecutive Chinese patients (median age 58 years) to evaluate their unique clinical–biological profiles and treatment responses. Our Chinese population exhibited a distinct comorbidity spectrum, characterized by a lower prevalence of concurrent arthritis (2.9%) and secondary malignancies, compared with Western cohorts. At diagnosis, 31.4% of the cohort had neutropenia, 42.9% had anemia, and 31.4% had thrombocytopenia. The median large granular lymphocyte count was 3.9 × 10⁹/L (range 0.11–114.8 × 10⁹/L; IQR 1.9 × 10⁹/L, 5.9 × 10⁹/L). Immunophenotyping consistently identified as a CD3- CD56+ clone. Notably, genomic profiling via NGS revealed a STAT3 mutation rate of 14.3%. Regarding therapeutic efficacy, frontline immunosuppressive therapy with cyclophosphamide or cyclosporine was associated with favorable clinical responses (best overall response, complete remission rate 66.7% for both). Additionally, sirolimus emerged as a potentially highly effective salvage option, yielding an overall response rate of 85.7% (95%CI 42.1–99.6%) and complete remission rate of 57.1%. With an estimated 3-year overall survival rate of 85.6% (95%CI 73.3%, 99.8%), our findings suggest a generally indolent clinical course of NK-LGLL in this Chinese cohort and highlight the potential of mTOR inhibition in refractory cases, warranting further prospective investigation. Full article