Search Results (53)

Importance: Evidence regarding the organization of civilian health care systems in active war zones is limited, yet critical for maintaining services for vulnerable populations. Objective: To describe the operational challenges and adaptive strategies implemented by an opioid agonist therapy (OAT) clinic to ensure continuity of care for patients maintained on methadone and buprenorphine during a period of prolonged armed conflict. Design: A descriptive case study of clinical, logistical, and regulatory adaptations following the escalation of conflict in Israel beginning 7 October 2023, through the 12-day Israel-Iran war in June 2025. Setting: A hospital-based ambulatory methadone maintenance treatment (MMT) clinic in the Tel Aviv region. Participants: A vulnerable population of patients with opioid use disorder (OUD) receiving daily or supervised OAT. Exposure(s): National emergency conditions, including mass evacuations, fluctuating missile threats from multiple fronts (Gaza, Lebanon, Yemen), and direct regional strikes in 2024 and 2025. Main Outcome(s) and Measure(s): The primary focus was maintaining treatment continuity through rapid protocol modifications and expanded take-home dose (THD) regulations. Results: The conflict necessitated immediate departures from standard clinical protocols. Key adaptations included the rapid expansion of THD eligibility to mitigate the risks associated with travel to the clinic during active shelling and the reallocation of resources. Regulatory frameworks were iteratively revised as the security situation evolved, shifting from daily supervised dosing to flexible, safety-oriented dispensing models. Conclusions and Relevance: Findings suggest that during national emergencies, decentralizing OAT through expanded THD regulations is essential to prevent treatment interruption and relapse. These adaptive strategies offer a framework for health policy in other conflict-affected regions to protect high-risk populations. Full article

Preclinical studies and data from other cancers suggest that inhibition of the Hedgehog (Hh) pathway also has antiproliferative effects on glioma cells. A key component of this pathway is the Smoothened (SMO) protein, which is expressed in high-grade gliomas. Itraconazole (ITRA), a widely used antifungal agent, inhibits SMO, the PI3K/AKT/mTOR pathway, and the VEGF/VEGFR-2 axis—both of which are critical for GBM progression and angiogenesis. This protocol describes a prospective, single-center, dose-escalation phase I study with the classical 3 + 3 design in order to determine the MTD of ITRA. The study enrolls patients with a newly histologically confirmed diagnosis of GBM, without previous treatment except surgery. They will be treated with standard RT schedule (60 Gy in 30 fractions) with concurrent TMZ 75 mg/m² and ITRA 2 × 100 mg, 200 mg, or 300 mg daily. The primary endpoint is to determine the MTD of ITRA given concurrently with RT + TMZ. Secondary endpoints include safety and tolerability of ITRA, overall survival (OS), progression-free survival (PFS), overall objective response rate, use of corticosteroids, treatment compliance, and health-related quality of life (EORTC QLQ-C30 and BN20). Participants will be monitored for one week post-treatment. All relevant statistics will be primarily descriptive. Full article

Soil micro- and nanoplastic contamination is escalating globally, yet its potential to interfere with routine agrochemical analyses remains poorly quantified. Standard operating procedures (SOPs) were calibrated for natural soil matrices and may not account for synthetic, carbon-rich polymers. This controlled model study quantified the analytical sensitivity of FAO/GLOSOLAN/ISO standard procedures to polystyrene nanoparticle (50 nm) contamination across a 0–0.5% (w/w) gradient in a Luvic Chernozem. Key parameters—pH, soil carbon, total nitrogen (TN), cation exchange capacity (CEC), and clay fraction—were measured following standardized protocols. The Walkley–Black method exhibited a strong dose-dependent increase in measured SOC (r = 0.93), reflecting systematic overestimation due to dichromate co-oxidation of polymer matrix, likely facilitated by exothermic heating above polystyrene’s glass transition temperature. The Dumas method showed moderate correlation (r = 0.59) but higher replicate variability driven by small aliquot size and heterogeneous nanoparticle distribution. The pH measurements displayed non-linear responses and elevated variability at low doses, whereas TN, CEC, and clay content remained statistically stable. These findings demonstrate that nanoplastic contamination can introduce significant analytical artifacts in oxidation-based SOC determinations, potentially leading to misinterpretation of soil carbon trends. Given the single-soil, single-polymer design, results represent a system-specific proof of analytical vulnerability rather than a universally quantified bias. Laboratories analyzing potentially contaminated soils should exercise caution with wet-oxidation SOC data, and broader SOP revisions must await multi-soil, multi-polymer validation campaigns. Full article

Introduction: Peanut oral immunotherapy (P-OIT) is an emerging treatment strategy for peanut allergy (PA). Although a standardized pharmaceutical product, Peanut (Arachis hypogaea) Allergen Powder-dnfp, has been approved in several countries, it is not universally available. In such contexts, real-world protocols using readily utilizable peanut products may represent an alternative approach. This study aimed to describe the feasibility, safety, and clinical outcomes of P-OIT using toasted peanuts in a real-world effort in a pediatric population. Methods: This single-center retrospective cohort study enrolled children who initiated P-OIT at our tertiary pediatric hospital Allergy Unit between April 2015 and December 2024. Demographic and clinical features, allergy test results, and information about P-OIT were recorded. Desensitization was defined as tolerance of 630 mg of peanut protein (PP). Results: Sixty patients (51.7% male; median age 8.2 years) were included. 22/60 (36.7%) achieved desensitization within a median time of 22.7 months. 21/60 (35%) were still undergoing P-OIT at a median tolerated dose of 100 mg of PP, and 17/60 (28.3%) discontinued treatment, most commonly due to loss to follow-up (44%). At least one adverse reaction occurred in 43/60 (71.7%) patients, predominantly mild and self-limiting (68.3% resolved spontaneously, 39.5% occurred at home). However, 11/60 (18.3%) showed anaphylaxis, and 3/60 (5%) received adrenaline. A reduction in Ara h 2 serum-specific IgE levels compared to the baseline was observed in patients completing escalation (p = 0.03). Conclusions: In this real-world single-center cohort, P-OIT using toasted peanuts was feasible in a subset of patients and was associated predominantly with mild adverse reactions, although systemic reactions were also recorded. Treatment discontinuation and adherence remain relevant challenges. These findings highlight the need for prospective, controlled studies to better define the role, safety profile, and patient selection criteria for food-based P-OIT protocols in settings where standardized products are not available. Full article

Background: Diabetic foot ulcers recur frequently after healing. The first three months carry the highest risk. Remission is a vulnerable phase that demands precise self-care and timely feedback. Evidence supports thermometry and protective footwear with gradual return to activity, yet adherence at home is inconsistent. Objective: To describe the design and planned evaluation of a conversational agent (chatbot) that guides patients through the remission phase following diabetic limb reconstruction. Methods: This protocol describes a conversational agent (chatbot) that turns remission guidance into daily actions, grounded in clinical expertise and established care guidelines. Walking is dosed like a drug, with careful titration based on tissue response. The agent integrates automatic data capture (smartphone step counts, skin temperature, shoe step streams, smartwatch step streams, Bluetooth thermometry when available, and app session timestamps) with manual patient entries (shoe wear time, skin redness persistence, and symptom checks). It doses walking activity, guides footwear break-in, prompts photo-confirmed concerns, following clinician-informed rules and escalation pathways. We define data quality checks for missingness and physiologic plausibility, and the agent reinforces reducing weight-bearing activity when risk signals appear. We outline device drift. The study is designed as a single-arm feasibility pilot (n = 30) to assess engagement, safety, and implementation fidelity. Results: No clinical outcome results are reported because this is a protocol study and enrollment has not yet begun. This study presents the prespecified sensing-to-decision workflow, escalation logic, and pilot endpoints, along with internal technical verification procedures (e.g., message delivery reliability, data completeness checks, and rule-engine consistency testing). Conclusions: A remission chatbot is a plausible method to extend specialist support into the home, reflecting integration of clinical expertise with digital health tools. This protocol defines how feasibility, safety, and usability will be evaluated. Clinical efficacy should be confirmed in future studies. Full article

Chronic osteoarthritis (COA) is a progressive and degenerative condition that causes joint inflammation and pain, often requiring long-term pharmacological management. Conventional treatments may lead to adverse effects, tolerance, and limited analgesic efficacy. This randomized, double-blind clinical trial evaluated the analgesic potential of a full-spectrum Cannabis sativa oil extract administered orally twice daily over six weeks in dogs with COA. Subjects were assigned to three groups: Cannabis, Placebo, and Control. Pain was assessed using the Canine Brief Pain Inventory (CBPI) and the Canine Osteoarthritis Staging Tool (COAST), which ranges from 0 to 4. The Cannabis extract (46.4 mg/mL) total cannabinoids: Cannabidiol (CBD), Cannabidiolic acid (CBDA), Delta-9-Tetrahydrocannabinol (Δ⁹-THC), and Tetrahydrocannabinolic acid (THCA), were administered using a cautious dose escalation protocol. Treatment began at ~0.1 mg/kg every 12 h, increasing by one drop (1.16 mg) every 72 h. This gradual titration continued until reaching the maximum tolerated dose (2 mg/kg every 12 h), which was maintained for the final two weeks. The protocol was designed to minimize adverse effects and allow close monitoring, especially in geriatric or clinically fragile dogs. By day 28, when the DMT was reached, the Cannabis group showed a 39.6% reduction in CBPI scores, compared to 24.7% in the Placebo group and a 1.6% increase in the Control group. COAST scores improved from level 4 to level 3 in 55.5% of dogs in the Cannabis group, with no changes observed in the other groups. We hypothesize that the co-administration of carprofen, meloxicam, or pregabalin with a full-spectrum Cannabis sativa extract—rich in acidic cannabinoids and terpenes—enhances pain relief and mobility in dogs with COA more effectively than conventional therapies alone. This study aimed to assess the efficacy of an oily full-spectrum Cannabis sativa extract as an adjunctive treatment to NSAIDs in twenty-seven dogs diagnosed with COA, and to compare pain intensity across three treatments groups. Full article

Mono-antibiotic therapy for Helicobacter pylori (H. pylori) infection minimizes unnecessary antibiotic exposure, reduces disruption of the gut microbiota, and lowers the risk of multidrug resistance. Although resistance of H. pylori to amoxicillin remains extremely low (<3%) worldwide, regular-dose amoxicillin monotherapy achieves eradication rates of less than 30%. Strategies to improve the efficacy of amoxicillin-based mono-antibiotic therapy include elevating intragastric pH with potent acid suppression, increasing the amoxicillin dose, and adding bismuth salts to the treatment regimen. This review evaluates the safety and effectiveness of six amoxicillin-based treatments for H. pylori. All regimens lasted 14 days and were studied in clinical trials published between 1 October 2014, and 1 October 2025. The pooled intention-to-treat and per-protocol eradication rates for each regimen were as follows: Regimen 1: Regular-dose amoxicillin + high-dose proton pump inhibitor (PPI): 84.7% (83/98) and 84.7% (83/98); Regimen 2: High-dose amoxicillin + high-dose PPI: 85.3% (3709/4347) and 89.9% (3692/4109); Regimen 3: Regular-dose amoxicillin + high-dose potassium-competitive acid blocker (PCAB): 86.0% (901/1048) and 91.2% (888/974); Regimen 4: High-dose amoxicillin + high-dose PCAB: 88.2% (1771/2009) and 93.5% (1720/1839); Regimen 5: Regular-dose amoxicillin + high-dose PCAB + bismuth: 84.9% (327/385) and 91.3% (327/358); Regimen 6: High-dose amoxicillin + high-dose PCAB + bismuth: 95.8% (115/120) and 98.4% (115/117). In conclusion, potent acid inhibition, escalation of amoxicillin dosage, and incorporation of bismuth can transform amoxicillin mono-antibiotic therapy from an ineffective approach into a highly effective eradication regimen for H. pylori infection. Full article

Purpose of Review—sleep disturbance is the main complaint associated with patients who suffer acute postoperative pain. Sleep disturbance may also increase the pain sensitivity and contribute to the development and maintenance of chronic pain. The pathophysiology of pain is complex; management of perioperative pain and preventing chronic pain are challenges in clinical. Use of opioids for pain management are still a therapeutic mainstay and generally safe when taken, in a short time, for severe postoperative pain relief. For long-term use tolerance may be developed, and for their euphoric property, addiction, overdose incidents, and even death may be the social problems. Therefore, the opioid-sparing multimodal analgesia (MMA) for pain management is recommended in current postoperative pain management. The successful MMA for pain management will enhance patient recovery after surgery with less chronic CPSP and long-term opioid use disorder (OUD). The present review discusses all currently used analgesics actions and interactions, and opioid-sparing or opioid-free analgesia in perioperative pain management. Acute pain following major trauma or surgery may originate from both nociceptive and neuropathic mechanisms. Approximately 10–50% of surgical patients develop chronic postoperative pain, which not only causes persistent discomfort but also leads to functional limitations and psychological distress. Growing evidence highlights a close and bidirectional relationship between sleep and pain: pain disrupts sleep architecture, while sleep deprivation intensifies pain sensitivity and impairs recovery. This reciprocal interaction forms a vicious cycle that poses challenges for effective pain management. Melatonin—a neurohormone secreted by the pineal gland—plays a crucial role in regulating circadian rhythm and sleep–wake cycles. Beyond its chronobiotic action, melatonin exhibits anti-nociceptive, anti-inflammatory, and opioid-sparing properties. Recent preclinical studies have demonstrated that exogenous melatonin can attenuate nociceptive responses to noxious stimuli and enhance morphine analgesia while attenuating morphine tolerance. Moreover, environmental light manipulation preserving the circadian rhythm has been shown to synergistically maintain melatonin secretion, improve sleep quality, and modulate neuroimmune responses involved in pain regulation. Together, these findings suggest that circadian alignment and melatonin supplementation may represent a promising integrative approach for improving both pain control and sleep health in perioperative and chronic pain conditions. Chronic pain patients frequently experience opioid tolerance during long-term therapy, resulting in diminished analgesic efficacy and a need for escalating doses. Our recent work revealed that constant light exposure suppresses endogenous melatonin, heightens pro-inflammatory cytokines (TNF-α, IL-1β), reduces IL-10, and accelerates morphine tolerance in a neuropathic pain model. In contrast, maintaining circadian light–dark cycles or supplementing melatonin preserves melatonin rhythm, reduces glial activation, and sustains morphine antinociception. Melatonin’s co-administration not only attenuates morphine tolerance but also enhances morphine efficacy through the modulation of inflammatory and glial pathways. These findings underscore melatonin’s multifaceted role as both a chronotherapeutic and neuroprotective agent, integrating circadian regulation with pain modulation. Clinically, the application of melatonin or circadian-aligned strategies could guide personalized pain and sleep management, offering safer and more effective multimodal analgesic protocols with reduced opioid dependence and improved quality of life. Full article

Background/Objectives: Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) remains a major challenge in the treatment of EGFR-mutant lung adenocarcinoma (LUAD). This study aimed to develop and characterize representative models of acquired EGFR-TKI resistance and to identify potential therapeutic targets mediating this process. Methods: Resistant models of PC9 and LUAD-PDCs were generated using a standardized dose-escalation protocol. The resulting models were characterized by drug response assays, morphology, and transcriptomic sequencing. Candidate target genes were validated across all resistant models using siRNA knockdown followed by re-sensitization assays. Clinical relevance was further examined through analysis of publicly available datasets. Results: These generated models displayed stable resistant phenotypes and unique transcriptomic alterations. Cross-model analysis revealed MUC16 as a consistently upregulated gene associated with resistance. Functional validation demonstrated that MUC16 depletion re-sensitized all resistant models to EGFR-TKIs. Furthermore, analysis of clinical data linked high MUC16 expression to poorer patient outcomes. Conclusions: This study establishes stable in vitro models for investigating acquired resistance in EGFR-mutant LUAD and identifies MUC16 as a functionally validated and clinically relevant mediator of EGFR-TKI resistance, providing a potential therapeutic target for overcoming drug resistance. Full article

Background: Unfractionated heparin (UFH) is the standard anticoagulant during cardiopulmonary bypass (CPB). A clinically relevant subset develops heparin resistance (HR)—failure to reach adequate anticoagulation with usual UFH—raising thrombotic risk and complicating perioperative care. Objectives: To synthesize contemporary evidence on the mechanisms, clinical implications, and perioperative management of HR in adult cardiac surgery with CPB. Methods: This narrative review synthesizes contemporary evidence on the epidemiology, mechanisms, recognition, and management of HR in adult cardiac surgery with CPB, emphasizing clinically actionable points. Results: Incidence varies across centers and definitions. Mechanisms include antithrombin (AT) deficiency or consumption and AT-independent drivers such as systemic inflammation or sepsis, protein-loss states, thrombocytosis, hyperfibrinogenemia, obesity, prior heparin exposure, and drug interactions. Sole reliance on activated clotting time (ACT) may misestimate anticoagulant effect; anti–factor Xa (anti-Xa) assays or heparin titration systems improve assessment when available. Management is stepwise: UFH dose escalation; targeted AT supplementation (or fresh frozen plasma where concentrates are unavailable); and transition to direct thrombin inhibitors when HR persists or UFH is contraindicated. Protocolized pathways and multidisciplinary coordination reduce delays and adverse events. Conclusions: HR is a multifactorial, common challenge in CPB. Pre-bypass risk assessment, multimodal monitoring, and an algorithm prioritizing UFH optimization, AT repletion, and timely use of direct thrombin inhibitors provide a pragmatic framework to limit thrombosis and bleeding. Harmonized definitions and comparative trials remain priorities. Full article

Background and Objectives: External ventricular drain (EVD)-associated infections are a serious complication in subarachnoid hemorrhage (SAH) patients, with reported incidence rates of 1–45%. Existing prediction models show limited performance and focus on the static risk factors assessed at insertion, failing to examine how infection risk changes over time. We sought to identify the independent predictors of EVD infections in SAH patients and develop a practical clinical prediction model. Materials and Methods: We retrospectively analyzed 198 SAH patients with EVDs treated at our center between January 2022 and April 2025, collecting 4757 laboratory observations throughout their hospital stay. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors and develop a clinical prediction model. Results: Of 198 patients undergoing EVD insertion for SAH, 49 developed associated infections (24.7%). Univariate analysis identified several significant risk factors, including EVD duration (Cohen’s d = 1.00, p < 0.001), EVD revisions (d = 1.11, p < 0.001), Hunt & Hess grade ≥ 4 (p = 0.011), and peak laboratory values, including CSF lactate (d = 0.53, AUC = 0.79), CSF protein (d = 0.52, AUC = 0.74), CSF glucose (d = 0.63, AUC = 0.73), and procalcitonin (d = 0.58, AUC = 0.75). However, multivariate analysis revealed that only EVD duration retained statistical significance (adjusted OR = 3.50 per continuous day; 95% CI: 2.11–5.78; p < 0.000001); note that continuous daily scale modeling implies exponential risk escalation (3.5-fold increase per single day). For clinical interpretation, categorical duration analysis provides more conservative estimates: 8–14 days versus ≤7-day reference OR = 1.92 (p = 0.013), and >14 days versus ≤7-day reference OR = 3.70 (p < 0.001). All other variables lost statistical independence after mutual adjustment. Infection rates demonstrated a dose–response relationship with EVD duration: 11.1% for ≤7 days, 19.3% for 8–14 days, and 31.6% for >14 days. The final prediction model achieved good discrimination (AUC = 0.737). Conclusions: EVD duration emerged as the dominant predictor of infection risk in SAH patients, which is a traditional factor. These findings support clinical protocols that prioritize minimizing drain duration whenever medically appropriate, shifting focus from complex risk scoring to time-based management strategies. Full article

Background/Objectives: Optimization of pediatric head computed tomography (CT) protocols is essential to minimize radiation exposure while maintaining diagnostic image quality. Previous studies mainly relied on phantom-based measurements or visual assessments, and validation using clinical images remains limited. This study aimed to establish quantitative thresholds for noise and contrast-to-noise ratio (CNR) in pediatric head CT by integrating multicenter clinical data with phantom evaluations. Methods: A multicenter retrospective study was conducted using CT systems from eight hospitals, combined with Catphan phantom experiments and pediatric head CT data. Scan parameters, automatic exposure control settings, and reconstruction methods were collected. Image quality was quantified by the standard deviation (SD) of noise and CNR obtained from regions of interest in gray and white matter. Radiation dose was represented by CTDIvol. Relationships among CTDIvol, SD, and CNR were analyzed across scanners from three manufacturers (Canon, FUJI, and GE). Results: Consistent dose–response trends were observed across institutions and manufacturers. Image noise decreased as CTDIvol increased, but reached a plateau at higher doses. CNR improved with dose escalation, then stabilized. Both phantom experiments and clinical analyses identified a target SD of 5 and CNR of 2 as optimal indicators for pediatric head CT. Conclusions: Quantitative thresholds were determined as practical indicators for balancing diagnostic image quality with dose reduction. Further reduction may be achieved through advanced reconstruction methods, such as deep learning-based algorithms. These findings may contribute to standardizing pediatric head CT protocols and supporting safer and more effective diagnostic imaging. Full article

Therapeutic plasma exchange (TPE) is increasingly recognized as a critical escalation therapy for managing acute multiple sclerosis (MS) relapses refractory to high-dose corticosteroids. Neuropathological and clinical evidence implicate humoral immune mechanisms, particularly autoantibodies, immune complexes, and complement activation, as key pathogenic drivers in a subset of MS attacks, notably those consistent with immunopathological pattern II. By removing these circulating immune effectors, TPE provides a rational strategy to dampen inflammation and promote neurological recovery. This review integrates current mechanistic insights with clinical efficacy data and practical implementation strategies for TPE in corticosteroid-refractory MS. Evidence from randomized controlled trials and observational cohorts demonstrates moderate-to-marked functional improvement in 40–60% of patients, with the greatest benefit observed when therapy is initiated within 14 days of symptom onset and cases demonstrating active inflammatory lesions on MRI. Predictors of a favorable response include younger age, short disease duration, severe syndromes involving optic nerve, brainstem, or spinal cord, and CSF markers of intrathecal B-cell activity. Although TPE is generally well tolerated in experienced centers, its broader adoption of TPE is limited by variability in access, institutional protocols, and provider familiarity. Standardization of treatment algorithms, validation of predictive biomarkers, and incorporation into streamlined clinical pathways are critical to maximizing its clinical impact. Future priorities include comparative trials against alternative escalation therapies, biomarker-guided patients’ selection, and comprehensive health-economic evaluations. Taken together, current evidence and recommendations from major neurology and apheresis societies support TPE as a valuable therapeutic modality capable of significantly improving relapse outcomes in appropriately selected MS patients. Full article

Background: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare auto-inflammatory condition affecting the growing skeleton. The standard first-line treatment of high-dose NSAIDs (non-steroidal anti-inflammatory drugs) is adequate only in a subset of patients. The American College of Rheumatology Consensus Guidelines suggest considering bisphosphonates in a certain category of patients based on evidence from a handful of case series reporting the outcome of pamidronate use. Aims: The aim of this study was to report the efficacy and safety of bisphosphonate, predominantly zoledronate, use in CRMO. Methods: A retrospective cohort study of children with CRMO receiving bisphosphonates was conducted between January 2008 and September 2023 at a single tertiary referral centre. We described the baseline characteristics; clinical indication, regimen and response to bisphosphonate treatment; changes in bone mineral density (BMD) and spine remodelling on dual-energy X-ray absorptiometry (DXA) scans; and safety data. Results: During the study period, 64 (72%, n = 46 females) patients with CRMO with a median age at diagnosis of 10 years (range: 3 to 16 years) were identified. Approximately 31% (n = 20) received either pamidronate (n = 2) or zoledronate (n = 14) or both (n = 4) due to changes in local protocols. The most frequent indications for bisphosphonate use were refractory pain [55%, n = 11/20], pain + spine involvement [35% (n = 7/20)] and spine involvement only [10% (n = 2)]. Prior to bisphosphonate therapy, 100% took regular NSAIDs (n = 19/19), 21% (n = 4/19) used opioids, 47% (n = 9/19) received oral steroid courses, and 10% (n = 2/19) received methotrexate. The median age at bisphosphonate treatment initiation was 12 years (range 6–18 years), and the duration of treatment was 2 years (range: 6 months to 5 years). Improvement in pain was reported by 88% of patients (n= 15/17, 1 was excluded as they had not started treatment yet). All non-responders (n = 2/17;) to bisphosphonate therapy were later recognised clinically to have pain amplification syndrome and were referred to the chronic pain multi-disciplinary team. This correlated to the complete treatment de-escalation of opioids (n = 3/3; 1 was excluded as they had not yet started treatment), steroids (n = 8/8) and methotrexate (n = 2/2). NSAIDs were discontinued in 44% of patients (n = 7 of 16; 1 was excluded due to missing data, and 3 were excluded due to NSAID intolerance). The median first-year increase in the LS BMAD (lumbar spine bone mineral apparent density) Z-score was +1.35, and that in the TBLH BMD (total body less head bone mineral density) Z-score was +0.7 (n = 11). Subsequently, median average annual increases in the LS BMAD Z-score of +0.65 and in the TBLH BMD Z-score of +0.45 (n = 5) were recorded. Around 30% of patients (n = 6) required treatment modification (dose reduction, frequency reduction or cessation) due to a rapid escalation in BMD. There were no fractures documented due to raised BMD. Evidence of spine remodelling on DXA vertebral fracture assessment was seen in 38% of patients with spinal lesions (n = 3 of 8). There was no radiological evidence of improvement in any vertebra plana lesion. First-phase reactions (pyrexia) were reported universally in patients who received bisphosphonates, but none were significant requiring hospitalisation. Conclusions: Similar to pamidronate, zoledronate with an advantageous dosing regimen is well tolerated and effective in improving pain and enabling the de-escalation of adjunctive therapy in CRMO. This is the first report tracking changes in BMD and spinal remodelling in response to zoledronate in CRMO patients. Spinal remodelling is minimal in vertebra plana lesions. Bone density monitoring and personalisation of the bisphosphonate dose and regimen are strongly recommended to avoid overtreatment. Full article

Background and Objectives: Total body irradiation (TBI) remains a cornerstone of conditioning for allogeneic haematopoietic stem-cell transplantation (HSCT). Whereas early research debated the need for irradiation, contemporary investigations focus on optimising dose, fractionation and delivery techniques. Material and Methods: We synthesised six decades of evidence, spanning from single-fraction cobalt treatments to modern helical tomotherapy and intensity-modulated total-marrow/lymphoid irradiation (TMI/TMLI). To complement the literature, we reported our institutional experience on 77 paediatric and adult recipients treated with conventional extended-source-to-skin-distance TBI at the University Hospital Policlinico “G. Rodolico–San Marco” between 2015 and 2025. Results: According to literature data, fractionated myeloablative schedules, typically 12 Gy in 6 fractions, provide superior overall survival and lower rates of severe graft-versus-host disease (GVHD) compared with historical single-dose regimens. Conversely, reduced-intensity protocols of 2–4 Gy broaden HSCT eligibility for older or comorbid patients with acceptable toxicity. Conformal planning reliably decreases mean lung dose without compromising engraftment, and early-phase trials are testing selective escalation to 16–20 Gy or omission of TBI in molecularly favourable cases. With regard to our institutional retrospective series, 92% of patients completed a 12-Gy regimen with only transient grade 1–2 nausea, fatigue or hypotension; all transplanted patients engrafted, and no grade ≥ 3 radiation pneumonitis occurred. Conclusions: Collectively, the published evidence and our experience support TBI as an irreplaceable component of HSCT conditioning and suggest that coupling it with advanced imaging, organ-sparing dosimetry and molecular response monitoring can deliver safer, more personalised therapy in the coming decade. Full article