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POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein level, and skin changes) syndrome is a rare multisystem, autoinflammatory condition resulting from underlying plasma cell neoplasm. Arterial and venous thromboses, in addition to third space oedema may be under-recognised features of the disease.We present the case of a 62 year old man with a progressive subacute distal symmetrical sensorimotor neuropathy with concurrent TIAs, pleural effusions and cardiac tamponade necessitating pericardial drainage. NCS confirmed severe sensorimotor demyelinating polyneuropathy. CSF was acellular with raised protein. Immunofixation demonstrated a monoclonal IgA Lambda band and VEGF levels were over 10,000pg/ml. CT-guided biopsy of an L1 osteosclerotic lesion showed an increased number of plasma cells. MRI brain with contrast revealed diffuse pachymeningeal enhancement and a CT venogram confirmed incidental venous sinus thrombosis. He was commenced on chemotherapy, as well as antiplatelet and anticoagulation agents as treatment for his cerebrovascular complications.High rates of venous and arterial thrombotic events occur in patients with POEMS. Whilst lower limb oedema is a characteristic finding, other forms of extravascular volume overload can occur such as pericardial and pleural effusions. This case highlights the importance of recognition and management of these features and complications of POEMS, to aid in both diagnosis and management.rachaelmatthews1990@gmail.com

A 54-year-old male presented with initial symptoms suggestive of a transient ischemic attack (TIA), including tingling and word-finding difficulty, which was initially attributed to a migraine. Over the next few months, he developed right thigh pain, a change in gait, and progressive weakness. He subsequently experienced paraesthesia, coldness, and numbness in both feet, leading to ”furniture walking” and a sensation of increasing heaviness in his legs. Peripheral oedema also developed and progressively worsened. CT imaging revealed splenomegaly, and neurological examination showed areflexia, reduced lower limb power, and inability to perform tandem walking. Laboratory results revealed a significantly elevated lambda light chain (116.3 mg/L) and an IgG lambda paraprotein. Bone marrow aspirate indicated monoclonal gammopathy of undetermined significance (MGUS). The diagnosis was clinched with an MRI of the right femur which revealed a plasmacytoma, and further investigations confirmed the diagnosis of POEMS syndrome. The patient later slipped and suffered a neck of femur fracture secondary to the plasmacytoma. This case highlights the complexity of diagnosing POEMS syndrome, which can present with diverse symptoms, including peripheral neuropathy, oedema, and plasmacytoma, and emphasizes the importance of a comprehensive diagnostic approach.lindalei93@gmail.com

Preclinical models of stroke have shown that intravenous glyburide reduces brain swelling and improves survival. We assessed whether intravenous glyburide (RP-1127; glibenclamide) would safely reduce brain swelling, decrease the need for decompressive craniectomy, and improve clinical outcomes in patients presenting with a large hemispheric infarction. For this double-blind, randomised, placebo-controlled phase 2 trial, we enrolled patients (aged 18–80 years) with a clinical diagnosis of large anterior circulation hemispheric infarction for less than 10 h and baseline diffusion-weighted MRI image lesion volume of 82–300 cm3 on MRI at 18 hospitals in the USA. We used web-based randomisation (1:1) to allocate patients to the placebo or intravenous glyburide group. Intravenous glyburide was given as a 0·13 mg bolus intravenous injection for the first 2 min, followed by an infusion of 0·16 mg/h for the first 6 h and then 0·11 mg/h for the remaining 66 h. The primary efficacy outcome was the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0–4 at 90 days without undergoing decompressive craniectomy. Analysis was by per protocol. Safety analysis included all randomly assigned patients who received the study drug. This trial is registered with ClinicalTrials.gov, number NCT01794182. Between May 3, 2013, and April 30, 2015, 86 patients were randomly assigned but enrolment was stopped because of funding reasons. The funder, principal investigators, site investigators, patients, imaging core, and outcomes personnel were masked to treatment. The per-protocol study population was 41 participants who received intravenous glyburide and 36 participants who received placebo. 17 (41%) patients in the intravenous glyburide group and 14 (39%) in the placebo group had an mRS score of 0–4 at 90 days without decompressive craniectomy (adjusted odds ratio 0·87, 95% CI 0·32–2·32; p=0·77). Ten (23%) of 44 participants in the intravenous glyburide group and ten (26%) of 39 participants in the placebo group had cardiac events (p=0·76), and four of 20 had serious adverse events (two in the intravenous glyburide group and two in the placebo group, p=1·00). One cardiac death occurred in each group (p=1·00). Intravenous glyburide was well tolerated in patients with large hemispheric stroke at risk for cerebral oedema. There was no difference in the composite primary outcome. Further study is warranted to assess the potential clinical benefit of a reduction in swelling by intravenous glyburide. Remedy Pharmaceuticals.

PurposeTo demonstrate the efficacy and safety of ranibizumab 0.5 mg pro re nata (PRN) versus laser photocoagulation for the treatment of Chinese patients with visual impairment due to diabetic macular edema (DME).MethodsREFINE was a phase III, 12-month, double-masked, multicenter, laser-controlled study in patients (aged ≥ 18 years) with DME. Patients were randomized 4:1 to receive either ranibizumab 0.5 mg or laser dosing regimen. Efficacy was evaluated as mean average change in best-corrected visual acuity (BCVA) from Months 1 to 12 versus baseline (primary endpoint), anatomical outcomes, treatment exposure, and safety were also assessed.ResultsRanibizumab was statistically superior (p < 0.001) to laser treatment, with a mean average BCVA gain of 6.8 letters (ranibizumab) over 12 months versus 1.1 letters (laser). At Month 12, mean BCVA gain was 7.8 letters (ranibizumab) and 2.5 letters (laser) from baseline. Patients in the ranibizumab arm received a mean number of 7.9 intravitreal injections, whereas those in the laser arm received a mean of 2.1 treatments. There were no new safety signals.ConclusionRanibizumab 0.5 mg PRN demonstrated a statistically significant and clinically meaningful treatment effect versus laser and was well tolerated in Chinese patients with visual impairment due to DME over 12 months.

Diabetic macular edema (DME) is a major cause of visual impairment, and treatment response can vary based on retinal structural changes. This post-hoc analysis of the Phase III VISTA trial evaluated ellipsoid zone (EZ) integrity and fluid dynamics over 100 weeks using a machine learning-enabled OCT segmentation and feature extraction platform. Among 443 eyes randomized to intravitreal aflibercept injections (IAI) or laser photocoagulation, IAI treatment provided greater reductions in intraretinal fluid volume (− 0.933 ± 1.344 mm 2 vs. − 0.386 ± 1.080 mm 2 ; p  < 0.0001) and better preservation of EZ integrity (− 24.6% vs. + 125.6%; p  < 0.0001) compared to laser. The IAI every 4 weeks (2q4) regimen achieved the most sustained improvement in fluid control, while increased fluid volatility in the IAI every 8 weeks (2q8) group was associated with poorer visual outcomes. In contrast, laser treatment was associated with early reduction in EZ integrity, consistent with known effects of photocoagulation, which this study quantified in vivo over time. At week 100, EZ integrity strongly correlated with best-corrected visual acuity ( r  = 0.61, p  < 0.05). No significant differences in treatment response were observed across racial/ethnic groups. These findings highlight the importance of consistent fluid control and demonstrate the utility of machine learning-derived EZ metrics and fluid stability as imaging biomarkers to guide personalized treatment strategies and optimize long-term visual outcomes. Registry : ClinicalTrials.gov, TRN: NCT01363440, Registration date: 27 May 2011.

A 54 year old lady was referred with a eighteen month history of slowly progressive, asymmetric, periorbital and facial oedema. She was thought to have inflammatory orbital pseudotumour.During this time, she had also developed a dry mouth, joint pains and enlarged salivary glands. A salivary gland ultrasound scan was suggestive of Sjogren’s disease although antinuclear antibody and rheumatoid factor were negative. She had recently been prescribed omeprazole for mild dysphagia and hoarse voice from vocal cord oedema.Past medical history included Hashimoto thyroiditis for which she was taking levothyroxine.Clinical examination revealed peri-orbital and facial oedema causing proptosis of the right globe and complete lid closure. Visual acuity, eye movements and visual fields of the left eye were normal. Her voice was hoarse and she had mouth ulcers. She had a widespread erythematous rash that was thought to be a drug reaction to omeprazole.Apart from mild lymphopenia and mildly deranged liver function, blood tests, including inflammatory markers and thyroid function, were unremarkable.MRI of the brain and orbits revealed diffuse oedema of facial structures, including the orbital muscles. A CT body scan was unremarkable.A temporalis muscle biopsy confirmed a high grade NK/T cell lymphoma.

PurposeTo assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU).MethodsPatients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control).ResultsOver the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed.ConclusionApproximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration.

No treatment is available to prevent brain oedema, which can occur after a large hemispheric infarction. Glibenclamide has previously been shown to improve functional outcome and reduce neurological or oedema-related death in patients younger than 70 years who were at risk of brain oedema after an acute ischaemic stroke. We aimed to assess whether intravenous glibenclamide could improve functional outcome at 90 days in patients with large hemispheric infarction. CHARM was a phase 3, double-blind, placebo-controlled, randomised trial conducted across 143 acute stroke centres in 21 countries. We included patients aged 18–85 years with a large stroke, defined either by an Alberta Stroke Program Early CT Score (ASPECTS) of 1–5 or by an ischaemic core lesion volume of 80–300 mL on CT perfusion or MRI diffusion-weighted imaging. Patients were randomly assigned in a 1:1 ratio to either intravenous glibenclamide (8·6 mg over 72 h) or placebo. The study drug was started within 10 h of stroke onset. The primary efficacy outcome was the shift in the distribution of scores on the modified Rankin Scale at day 90, as a measure of functional outcome. The primary efficacy outcome was analysed in a modified intention-to-treat population, which included all randomly assigned patients aged 18–70 years. The safety population comprised all randomly assigned patients who received a dose. This trial is registered with ClinicalTrials.gov (NCT02864953). The trial was stopped early by the sponsor for strategic and operational reasons (slow enrolment because of COVID-19), before any unblinding or knowledge of the trial results. Between Aug 29, 2018, and May 23, 2023, 535 patients were enrolled and randomly assigned, of whom 518 received a dose (safety population) and 431 were aged 18–70 years and comprised the modified intention-to-treat population (217 were assigned glibenclamide and 214 placebo). The mean age of patients was 58·7 (SD 9·0) years in the placebo group and 58·0 (9·5) years in the glibenclamide group; the median US National Institutes of Health Stroke Scale (NIHSS) score was 19 (IQR 16–23) in the placebo group and 19 (IQR 16–22) in the glibenclamide group; and the mean time from stroke onset to study drug start was 8·9 h (SD 2·1) in the placebo group and 9·2 h (2·1) in the glibenclamide group. Intravenous glibenclamide was not associated with a favourable shift in the modified Rankin scale at 90 days (common odds ratio [OR] 1·17 [95% CI 0·80–1·71], p=0·42). 90-day mortality was 29% (61 of 214) in the placebo group and 32% (70 of 217) in the glibenclamide group (hazard ratio 1·20 [0·85–1·70]; p=0·30). Serious adverse events in the prespecified safety population were consistent with the known safety profile of glibenclamide and included hypoglycaemia in 15 (6%) of 259 patients in the glibenclamide group and in four (2%) of 259 patients in the placebo group, leading to dose interruption or reduction in seven (3%) patients in the glibenclamide group and in one (<1%) in the placebo group. Intravenous glibenclamide did not improve functional outcome in patients aged 18–70 years after large hemispheric infarction, although the trial was underpowered to make definitive conclusions because it was stopped early. Future prospective evaluation could be warranted to identify a possible benefit of intravenous glibenclamide in specific subgroups. Biogen.

BackgroundGlibenclamide has garnered attention due to its multifaceted neuroprotective effects in cases of acute central nervous system injury. We initiated a trial to explore the effectiveness and safety of a high dose of glibenclamide in the management of cerebral oedema following aneurysmal subarachnoid haemorrhage (aSAH).MethodsThis trial constituted a single-centre, randomised clinical study. Half of the 56 patients assigned to the glibenclamide group received 15 mg of glibenclamide tablets daily for 10 days (5 mg, three times/day). The primary outcome was the proportion of patients achieving the subarachnoid haemorrhage early brain oedema score dichotomy (defined as Subarachnoid Haemorrhage Early Brain Oedema Score 0–2) at the 10-day postmedication. The secondary outcome of cerebral oedema was the concentration of sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) in the plasma and cerebrospinal fluid.ResultsWe enrolled 56 patients diagnosed with aSAH, who were admitted to the neurosurgery intensive care unit between 22 August 2021 and 25 April 2023. The primary outcome revealed that the glibenclamide group exhibited a notably higher proportion of mild cerebral oedema in comparison to the placebo group (60.7% vs 42.9%, adjusted OR: 4.66, 95% CI 1.14 to 19.10, p=0.032). Furthermore, the concentration of SUR1-TRPM4 in the cerebrospinal fluid of the glibenclamide group was significantly higher than the placebo group (p=0.0002; p=0.026), while the plasma TRPM4 concentration in the glibenclamide group was significantly lower than the placebo group (p=0.001).ConclusionOral administration of high-dose glibenclamide notably reduced radiological assessment of cerebral oedema after 10 days of medication. Significant alterations were also observed in the concentration of SUR1-TRPM4 in plasma and cerebrospinal fluid. However, it is worth noting that glibenclamide was associated with a higher incidence of hypoglycaemia. Larger trials are warranted to evaluate the potential benefits of glibenclamide in mitigating swelling and then improving neurological function.Trial registration numberChiCTR2100049908.