Search Results (212)

Background/Objectives: Benign prostatic hyperplasia (BPH) is a prevalent condition in aging men and a major cause of lower urinary tract symptoms (LUTSs). While traditional treatments such as transurethral resection of the prostate (TURP) are effective, they are associated with notable morbidity. Ultrasound-guided transperineal laser ablation (TPLA) has emerged as a minimally invasive alternative. This study aimed to assess the 12-month efficacy, safety, and functional outcomes of TPLA in patients with LUTS secondary to BPH. Methods: This was a single-center, retrospective observational cohort study including 53 patients with moderate-to-severe LUTS due to BPH who underwent TPLA between November 2021 and May 2024. Baseline and follow-up assessments were conducted at 1, 3, 6, and 12 months, including IPSS, Qmax, PVR, prostate volume (MRI), QoL, IIEF-5, and MSHQ-ED/Bother scores. The procedure was performed under local anesthesia using the EchoLaser™ system, and ablation was guided via real-time transrectal ultrasonography. Results: Statistically significant improvements were observed in IPSS (median decrease from 30 to 13), Qmax (5.5 to 13.0 mL/s), and PVR (200 to 85 mL). Prostate and adenoma volumes decreased by 41.2% and 58.3%, respectively. Quality of life scores improved, and erectile function remained stable. Ejaculatory function improved significantly based on MSHQ-ED and MSHQ-Bother scores. No major complications or conversions to surgery occurred. Conclusions: TPLA appears to be a safe, effective, and minimally invasive treatment modality for LUTS caused by BPH. It offers sustained symptomatic relief, prostate volume reduction, and preservation of sexual function, making it a promising alternative for patients unfit or unwilling to undergo invasive surgery. Full article

Background/Objectives: Penile urethral stricture is a therapeutically challenging condition that significantly impacts quality of life and is often managed initially with urethral dilation or internal urethrotomy. However, both techniques are associated with high recurrence rates, limited long-term efficacy, and potential adverse effects, particularly in the penile urethra. Urethroplasty remains the gold standard but is invasive and not suitable for all patients. Optilume, a paclitaxel-coated balloon, combines mechanical dilation with localized drug delivery to reduce recurrence rates and the need for re-intervention. This study evaluated its effectiveness in patients with penile urethral strictures. Methods: A retrospective, multicenter study was conducted at two German clinics. Eight male patients (mean age 59) with symptomatic penile urethral strictures underwent Optilume treatment. Symptom severity was assessed using the International Prostate Symptom Score (IPSS) and quality of life (QoL) scores before and after treatment. The primary endpoint was symptom improvement, while the secondary endpoint was the need for reintervention. Patients were followed for a median of 16.5 months. Statistical analyses included Wilcoxon signed-rank and Mann–Whitney U tests. Results: The median IPSS improved from 25.5 to 5.0 and QoL scores from 4.5 to 1.0 after treatment (p < 0.01 for both). No patients required reintervention during follow-up. The subgroup analysis showed slightly better outcomes in patients without prior interventions, although differences were not statistically significant. The stricture length did not correlate with treatment response. Conclusions: Optilume significantly reduces urinary symptoms and improves QoL in penile urethral strictures, and the absence of re-interventions during follow-up underscores its durable mid-term success. It offers a minimally invasive alternative to urethroplasty, particularly for patients seeking symptom relief with a shorter recovery time and no hospital stay or general anesthesia. These preliminary findings suggest that Optilume may be a promising minimally invasive option for selected patients. Larger, controlled studies are warranted to validate these results and refine patient selection criteria. Full article

Objectives: Silodosin, a selective α1A-adrenoceptor antagonist, is used to treat lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Genetic polymorphisms in drug-metabolizing enzymes and transporters may contribute to interindividual variability in its efficacy and safety. This study aimed to investigate the influence of CYP3A4, CYP3A5, UGT2B7, and ABCB1 polymorphisms on silodosin pharmacokinetics, efficacy, and safety in Russian patients with BPH. Methods: A prospective observational study included 103 Russian male patients with moderate-to-severe LUTS (IPSS > 8) due to BPH, treated with silodosin (8 mg daily) for 8 weeks. Genotyping for CYP3A4*1B, CYP3A4*22, CYP3A5*3, UGT2B7 (rs73823859, rs7439366, and rs7668282), and ABCB1 (rs4148738, rs1045642, rs2032582, and rs1128503) was performed using real-time PCR. The silodosin minimum steady-state plasma concentration (Css min) was measured via HPLC-MS. Efficacy was evaluated by the International Prostate Symptom Score (IPSS), quality of life scale, maximum urinary flow rate (Qmax), residual urine volume (RUV), and prostate volume at the baseline and week 8. Adverse drug reactions (ADRs) were recorded. Results: CYP3A4*22 CT carriers (n = 6) exhibited higher Css min (17.59 ± 2.98 vs. 9.0 ± 10.47 ng/mL, p = 0.049) but less absolute IPSS improvement (p < 0.05), likely due to higher baseline symptom severity. However, the change in IPSS (ΔIPSS_1–4) from the baseline to week 8 did not differ significantly (−5.78 ± 5.29 vs. −6.0 ± 4.54, p = 0.939). CYP3A5*3 GG homozygotes (n = 96) showed greater ΔIPSS_1–4 improvement (−6.25 ± 4.60 vs. 0.0 ± 9.53, p = 0.042) and a lower IPSS at day 28 (7.64 ± 4.50 vs. 20.0 ± 6.55, p < 0.001). UGT2B7 rs7439366 TT carriers (n = 34) had an improved Qmax (ΔQmax_1–4 5.4 vs. 3.3 and 2.0 mL/s for CC and CT, p = 0.041). ABCB1 1236C>T TT homozygotes (n = 25) showed a trend toward reduced RUV (p = 0.053). No polymorphisms were associated with adverse drug reactions (15 events in 42 patients, 35.7%). Conclusions: Genetic polymorphisms CYP3A4*22, CYP3A5*3, and UGT2B7 rs7439366 may modulate silodosin pharmacokinetics and efficacy parameters in BPH patients but not safety. Larger-scale studies are warranted to validate these initial findings. Full article

Background: Myelodysplastic syndromes are clonal hematopoietic disorders characterized by ineffective hematopoiesis and risk of progression to acute myeloid leukemia. Accurate prognostic stratification is essential to guide treatment, with several scoring systems in clinical use: IPSS, IPSS-R, and WPSS. Objective: We aimed to evaluate the prognostic accuracy of IPSS, IPSS-R, and WPSS in a real-world Romanian MDS cohort by comparing risk classifications with observed overall survival and progression-free survival. Methods: We conducted a retrospective analysis of 117 patients diagnosed with MDS treated in our clinic between 2018 and 2022. All patients had confirmed diagnoses based on bone marrow biopsy and cytogenetic testing. Data were used to assign risk categories based on IPSS, IPSS-R, and WPSS. Survival outcomes were analyzed using Kaplan–Meier curves and log-rank tests. Results: The median age of the cohort was 70 years; gender distribution was balanced. Transfusion dependence was present in 73.5%, and 49.6% had cytogenetic abnormalities. Overall, low-risk classification was assigned in 58.1% (IPSS), 38.5% (IPSS-R), and 38.5% (WPSS) of patients. Median OS was 20 months, and median PFS was 35 months. Although no statistically significant overall survival differences were observed across scoring systems, IPSS-R demonstrated a trend toward stronger prognostic discrimination in multivariable analysis. Reclassification of patients initially categorized as IPSS intermediate-1 revealed a significant survival impact: patients reclassified as lower-risk by IPSS-R and WPSS had a median OS of 67.5 months versus 15 months for those reclassified as higher-risk (IPSS-R: HR = 0.24; p = 0.0017; WPSS: HR = 0.26; p = 0.0031). Similarly, leukemic transformation occurred in 13.6% of reclassified lower-risk patients vs. 52.2% in higher-risk patients (IPSS-R: HR = 0.13; p = 0.0021; WPSS: HR = 0.12; p = 0.002), with a median PFS of 21 months in the higher-risk group. In multivariable Cox regression analysis, IPSS-R stratification remained a strong independent predictor for both OS (HR = 3.22; p = 0.000003) and PFS (HR = 4.77; p < 0.00001), while azacitidine treatment was associated with significantly improved survival (OS: HR = 0.43; p = 0.00002) and reduced risk of progression (PFS: HR = 0.36; p = 0.013). Full article

Background/Objectives: Lower urinary tract symptoms (LUTSs) due to benign prostatic obstruction (BPO) represent a common condition affecting aging men. Transurethral resection of the prostate represents the gold standard surgical treatment but is not without complications such as retrograde ejaculation, bleeding and urinary retention. The temporary implantable nitinol device (iTIND) is considered a minimally invasive surgical technique, designed to treat LUTS while preserving erectile and ejaculatory function. Herein we report the results of a multi-center, real-world assessment of the iTIND procedure. Methods: Data from five international centers treating LUTS with the iTIND device were collected. We recorded changes through an International Prostatic Symptom Score (IPSS) questionnaire with Quality of Life (QoL), International Index of Erectile Function (IIEF5) questionnaire, antegrade ejaculatory function, maximum flow (QMax), post voiding residual volume (PVR) and freedom from repeat intervention. Results: A total of 74 subjects were enrolled; median follow-up was 12 months. IPSS and QoL changed from a median of 23 and 4 points at baseline to 11 and 2 points, respectively, at the last follow-up. A mean improvement in Qmax and PVR from 9 mL/s and 56 mL at baseline to 13 mL/s and 40 mL was noticed at the last follow-up. Total median operative time was 10 min, and the median time of iTIND indwell time was 7 days. The median device removal time was 5 min. There were no changes in IIEF5 scores and antegrade ejaculation rate. No intraoperative complications were reported, and non-serious postoperative complications occurred in six patients (two urinary retention, two mild haematuria, two urinary tract infection). Finally, four patients underwent reoperation during the follow-up period. All procedures were performed as outpatient day cases. Conclusions: Our results confirms that treatment with the iTIND is effective and safe in terms of improving urinary symptoms and quality of life without impacting sexual function. Longer follow-up is required to better define the durability of this minimally invasive procedure. Full article

As the demand for context-aware services in smart environments continues to rise, Indoor Positioning Systems (IPSs) have evolved from auxiliary technologies into indispensable components of mission-critical infrastructure. This paper presents a comprehensive, multidimensional evaluation of IPSs through the lens of critical infrastructure, addressing both their technical capabilities and operational limitations across dynamic indoor environments. A structured taxonomy of IPS technologies is developed based on sensing modalities, signal processing techniques, and system architectures. Through an in-depth trade-off analysis, the study highlights the inherent tensions between accuracy, energy efficiency, scalability, and deployment cost—revealing that no single technology meets all performance criteria across application domains. A novel evaluation framework is introduced that integrates traditional performance metrics with emerging requirements such as system resilience, interoperability, and ethical considerations. Empirical results from long-term Wi-Fi fingerprinting experiments demonstrate the impact of temporal signal fluctuations, heterogeneity features, and environmental dynamics on localization accuracy. The proposed adaptive algorithm consistently outperforms baseline models in terms of Mean Absolute Error (MAE) and Root Mean Square Error (RMSE), confirming its robustness under evolving conditions. Furthermore, the paper explores the role of collaborative and infrastructure-free positioning systems as a pathway to achieving scalable and resilient localization in healthcare, logistics, and emergency services. Key challenges including privacy, standardization, and real-world adaptability are identified, and future research directions are proposed to guide the development of context-aware, interoperable, and secure IPS architectures. By reframing IPSs as foundational infrastructure, this work provides a critical roadmap for designing next-generation indoor localization systems that are technically robust, operationally viable, and ethically grounded. Full article

Secondary lymphoma of the prostate is described as the involvement of the prostate gland by lymphomatous spread from a primary site. This condition is exceedingly rare and often presents diagnostic and therapeutic challenges. The symptoms often mimic those of benign prostatic hyperplasia or prostate cancer, including LUTS (lower urinary tract symptoms) and even complete urinary retention. Here, we present a rare case of a 62-year-old male patient undergoing chemotherapy for stage IV mantle cell stomach lymphoma and subsequently secondary prostatic involvement. The patient presented with complete urinary retention, accompanied by biochemical (PSA = 11.7 ng/mL) and imaging (Magnetic Resonance Imaging-PIRADS V lesion) suspicion for prostate cancer. Histopathologic analysis of the MRI-targeted prostate fusion biopsy revealed secondary prostatic lymphoma. The chosen treatment was transurethral resection of the prostate (TUR-P) for relief of symptoms, which significantly improved urinary function (postoperative IPSS = 5 and Qmax = 17 mL/s). This case underscores the importance of considering prostatic lymphoma in the differential diagnosis of bladder outlet obstruction, especially in patients with a known lymphoma history. This report also provides a focused review of the literature on secondary prostatic lymphoma, highlighting the diagnostic challenges, treatment options, and clinical outcomes. Full article

Background: Phosphodiesterase type 5 inhibitors (PDE5i), particularly tadalafil and sildenafil, are the first-line therapies for erectile dysfunction (ED). After the patent expiration of branded tadalafil in 2017, generic formulations became available. Despite equivalent efficacy, skepticism persists regarding the effectiveness and safety of generics. The SHIFT study aimed to evaluate the non-inferiority of a generic tadalafil (Dalerpen) compared with branded and other generic tadalafil in terms of clinical efficacy and patient satisfaction. Methods: A prospective, multicenter study was conducted involving 247 patients treated with tadalafil (either 5 mg or 20 mg) for ED. Patients switched from branded or other generic tadalafil to Dalerpen. Baseline and follow-up assessments included the International Index of Erectile Function—Erectile Function Domain (IIEF-EF) (primary endpoint), Sexual Encounter Profile (SEP-2 and SEP-3), and International Prostatic Symptom Score (IPSS). A one-month follow-up was performed. Results: A total of 247 patients were included in the final analysis. After switching to Dalerpen, significant improvements were observed in both IIEF-EF (18.8 ± 5.6 vs. 16.7 ± 5.4, p < 0.001) and IPSS scores (10.4 ± 6.7 vs. 11.2 ± 6.3, p < 0.001), though the minimal clinically important difference (MCID) was not reached. SEP-3 scores also significantly increased (3 ± 1.2 vs. 2 ± 1.1, p < 0.001). Multivariate analysis identified baseline IIEF, IPSS scores, and post-treatment IPSS as predictors of IIEF-EF improvement (p < 0.001). Switching to Dalerpen was an independent predictor of both IIEF-EF and IPSS improvement. No new adverse events were reported. Conclusions: The SHIFT study demonstrates that Dalerpen is non-inferior to branded tadalafil in terms of clinical efficacy, offering a reliable and cost-effective therapeutic option. Educating patients on bioequivalence and addressing concerns regarding generic drugs are essential to facilitate therapeutic switches. Full article

Background and Objectives: While α1-blockers like silodosin are the mainstay for treating lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), combination therapy with phytotherapeutics may provide enhanced symptom control. Xipag^® is a novel formulation containing Graminex^® G96 (pollen extract) and Teupol^® 25P (teupolioside), offering anti-inflammatory and antiandrogenic effects. This study aimed to evaluate the efficacy of Xipag^® versus hexanic extract of Serenoa repens (HESr), both in combination with silodosin, in patients with LUTS/BPH. Materials and Methods: We conducted a single-center, prospective, observational, comparative study involving male patients with moderate-to-severe LUTSs undergoing treatment with silodosin. Patients were allocated to receive either Xipag^® or HESr in addition to silodosin, with follow-up every 3 months for 12 months. Primary outcomes included changes in symptom scores such as IPSS, QoL, and functional improvements such as peak urinary flow rate (Qmax). Multivariable regression analyses were used to assess predictors of the response. Results: Patients receiving Xipag^® showed significantly greater improvements in Qmax at all follow-up points (p < 0.05), with earlier and more sustained benefits compared to the HESr group. QoL index scores and PSA levels were also significantly better in the Xipag^® group starting from month six onward. IPSS scores improved in both groups but were significantly lower in the Xipag^® group only at 12 months (p = 0.04). No differences in erectile function (IIEF-5) or adverse events were observed. Conclusions: Xipag^® in combination with silodosin provides superior improvement in urinary flow, symptom-related QoL, and PSA reduction compared to HESr plus silodosin, with a favorable safety profile. These findings support the use of multi-target nutraceuticals like Xipag^® as a valuable adjunct in the management of LUTS/BPH. Larger randomized trials are warranted to confirm these results and explore underlying mechanisms. Full article

Background/Objectives: The pathogenesis of Myelodysplastic Syndrome (MDS) is diverse; however, increasing evidence suggests that inflammation and oxidative stress play a significant role in the development and progression of the disease. This study aimed to evaluate the prognostic impact of inflammation, nutritional status, and oxidative stress at diagnosis in patients with low-risk MDS. Methods: A retrospective analysis was conducted on 175 newly diagnosed low-risk MDS patients. Results: A low Prognostic Nutritional Index (PNI) and a high systemic oxidative stress (SOS) score were independently associated with poorer prognosis (PNI: HR 1.598, 95% CI 1.076–2.372, p = 0.02; SOS: HR 1.003, 95% CI 1.001–1.006, p = 0.002). The optimal PNI cut-off value for predicting mortality was identified as 47.47. Based on this cut-off, 92 patients had a low PNI score, while 83 patients had a high PNI score. The comparison between these groups revealed a statistically significant difference in median overall survival (OS), with 45.5 months for the low-PNI group and 75.1 months for the high-PNI group (p < 0.001). However, PNI was not significantly associated with progression to acute myeloid leukemia (AML) (p = 0.668). In the multivariate OS analysis, several factors were identified as independent predictors of prognosis, including a high Revised International Prognostic Scoring System (R-IPSS) score, low PNI, high SOS score, advanced age, male gender, and transformation to AML. Conclusions: Together, PNI and SOS may serve as simple, accessible tools to improve risk stratification in low-risk MDS patients. Full article

Background: Irreversible electroporation (IRE) is a novel ablative treatment modality for localized prostate cancer and aims at achieving oncological control while minimizing the related side effects. We present the functional and oncological outcomes of focal IRE ablation versus hemi-ablation from a single-center patient series. Methods: Men with histologically confirmed low–intermediate risk prostate cancer received focal IRE ablation or hemi-ablation. All the patients were recommended an MRI-targeted fusion biopsy plus systematic biopsy at 1 year post-IRE ablation. The functional outcomes were measured by the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) questionnaires. Results: In total, 106 patients were recruited in this study. The median follow-up time was 24 months (IQR 15–36). Overall, 94 patients underwent repeat prostate biopsy at 12 months after IRE. Persistent tumor was detected in 72.2% in the focal ablation group and in 31% in the hemi-ablation group (p < 0.001). Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 25% in the focal ablation group and in 8.6% in the hemi-ablation group (p = 0.003). There was no significant difference between the two groups in terms of IPSS and IIEF at each follow-up time point. Conclusion: For men with localized low–intermediate risk prostate cancer, hemi-IRE ablation treatment displayed better oncological control than focal ablation without compromising on functional or sexual outcomes. Full article

Background/Objectives: Prostate cancer is the second most common malignancy in men, and robot-assisted radical prostatectomy (RARP) has become a preferred treatment for localized disease. Postoperative urinary continence is a key determinant of quality of life. The aim of this study was to evaluate the preoperative patient characteristics and multiparametric magnetic resonance imaging (mpMRI) data that determine early postoperative continence in patients who underwent robotic radical prostatectomy at our clinic. Methods: In this study, patients who underwent robotic radical prostatectomy at our clinic between March 2020 and June 2022 were evaluated. The patients’ demographic data, preoperative PSA levels, digital rectal examination findings, preoperative lower urinary tract symptoms, sexual function, mpMRI findings, Briganti scores, surgical techniques used during the procedure and postoperative continence status were assessed. Results: A total of 111 patients were included in the study. The mean age of the patients was 61.1 years. The median follow-up duration was twelve months. According to the postoperative continence status, 22% of the patients were incontinent, 53% had moderate continence and 24% were fully continent in the first month. At the third month, 16.8% of the patients were incontinent, 31.3% had moderate continence and 51.8% were fully continent. At the one-year postoperative follow-up, the percentages of incontinent, moderately continent and fully continent patients were 4.8%, 13.2% and 81.9%, respectively. Urethral width in mpMRI (p: 0.012), pelvic transverse (p: 0.002) and AP (anterior–posterior) diameters (p: 0.033), preoperative IPSS scores (p: 0.033) and the presence of bilateral nerve-sparing surgery (p: 0.047) were found to be associated with postoperative urinary continence. No significant differences were found between groups regarding the relationship of other parameters evaluated by mpMRI with continence. Conclusions: In our study, preoperative IPSS scores, urethral width in mpMRI, pelvic transverse and AP diameters and the performance of nerve-sparing surgery were associated with early postoperative continence. Further studies with larger patient populations are needed to better understand the long-term predictors of postoperative urinary incontinence following radical prostatectomy. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is a common urological condition that can significantly impair quality of life in aging men by causing lower urinary tract symptoms (LUTS), including nocturia, weak stream, and incomplete emptying. While pharmacotherapy and surgical approaches such as transurethral resection of the prostate (TURP) remain cornerstone treatments, minimally invasive surgical therapies (MISTs) have emerged to bridge the gap between long-term medication use and invasive surgery. This narrative review assesses Rezūm therapy (water vapor thermal therapy, WVTT) by examining its mechanism of action, clinical efficacy, safety profile, and place in the BPH treatment algorithm. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs), prospective studies, real-world cohorts, and published systematic reviews with meta-analyses to provide a comprehensive evaluation of Rezūm therapy for BPH. Key outcomes assessed include changes in International Prostate Symptom Score (IPSS), urinary flow rates, retreatment rates, adverse events, and sexual function preservation. Results: Across multiple studies, Rezūm significantly reduces IPSS (typically by ≥50%) and increases peak urinary flow by 4–5 mL/s. These improvements are durable, with five-year follow-up data showing low retreatment rates of approximately 4–5% and sustained symptom relief. The procedure, performed under local or minimal anesthesia, has a favorable safety profile: most adverse events are mild or transient, and notable complications, such as bleeding requiring transfusion or persistent sexual dysfunction, are rare. Importantly, Rezūm preserves both erectile and ejaculatory function in most patients, setting it apart from many traditional surgical interventions associated with higher sexual side effect rates. Conclusions: Rezūm is an effective and minimally invasive alternative for men with moderate prostatic enlargement who desire durable symptom improvement while avoiding the morbidity and sexual side effects associated with more invasive surgery. Future research should aim to further refine patient selection and assess long-term outcomes in broader populations. Full article

Background: Vesicourethral anastomosis (VUA) is a critical step in radical prostatectomy (RP), with interrupted suture (IS) and running suture (RS) as common techniques. However, there is no conclusive evidence suggesting the superiority of one technique over the other regarding voiding function. This study compares their effects on voiding function and continence recovery after retropubic RP. Methods: A two-group, parallel-design study included 70 patients with localized prostate cancer (pT1-pT2) undergoing retropubic RP by a single surgical team. Patients were randomized to VUA with IS (n = 35) or RS (n = 35). The primary outcomes included uroflowmetry parameters—maximum flow rate (MFR), voiding volume (VV)—post-void residual volume (PVR), urinary function assessed by the International Prostate Symptom Score (IPSS), and continence recovery. These outcomes were measured preoperatively and at 1, 3, 6, and 12 months post-surgery. Secondary outcomes included surgical parameters, perioperative complications and one-year oncological outcomes. Results: Suturing time was shorter for RS than IS (21 vs. 33 min, p = 0.001). Minimal anastomotic leakage occurred more frequently in the IS group (23% vs. 9%), while long-term anastomotic stenosis rates were comparable between RS and IS groups (12% vs. 9%). IS demonstrated significantly higher MFR at 1-month post-surgery (23.3 vs. 17.2 mL/s, p = 0.003). In subsequent follow-ups (3, 6, and 12 months), the mean MFR remained higher in the IS group, though without statistical significance. Logistic regression favored IS for early MFR outcomes (OR 4.16; 95% CI, 1.22–14.18; p = 0.023). Continence recovery and IPSS scores were similar between groups. Conclusions: Both techniques are effective and safe. RS reduces suturing time and leakage risk, while IS improves early postoperative MFR. Full article

Background and Clinical Significance: Intermediate- to high-risk Myelodysplastic Syndrome (MDS), according to the Revised International Prognostic Scoring System (IPSS-M), confers a high risk of progression into acute myeloid leukemia. Treatment with hypomethylating agents, including azacitidine and decitabine, represents the current standard of care. In eligible patients, hypomethylating agents are used as a bridge for allogeneic stem cell transplantation, currently the only curative approach in these malignancies. The most common side effects of hypomethylating agents are myelosuppression, cutaneous injection site reactions (when azacitidine is given subcutaneously), and gastrointestinal symptoms. Uncommon, disabling, and long-lasting side effects represent a threat to effective treatment in this group of patients. Case Presentation: We describe the case of a 49-year-old male patient with IPSS-M intermediate-risk MDS, intended to receive first-line treatment with azacitidine followed by allogeneic stem cell transplantation. The first, late-onset azacitidine reaction was observed 48 h after the first exposure, with cutaneous and respiratory toxicity, followed by the late-onset recurrence of symptoms after azacitidine withdrawal and decitabine introduction. Conclusions: This case highlights atypical, disabling, and long-lasting drug reactions to two hypomethylating agents, with the persistence of hypersensitivity manifestations months after medication withdrawal. Full article