Central retinal vein occlusion in patients with metastatic solid tumors on tyrosine kinase inhibitors: a report of case series and literature review.

Background: Central retinal vein occlusion (CRVO) is a rare adverse effect related to the use of tyrosine kinase inhibitors (TKIs) in patients with metastatic malignancies, which has only been reported in several case reports. Case presentation: We reported the case series of three CRVO patients on regular regimens of TKIs as part of targeted therapies for metastatic malignancies, all of whom were otherwise healthy with no or well-controlled systemic conditions. All these patients received injections of intravitreal dexamethasone implant (IDI) and achieved a fluid-free macula at the end of the visit. In addition, we reviewed the existing literature on this subject and present here an updated analysis of the related TKIs, ocular presentation, treatment, and prognosis. Conclusion: All patients diagnosed with CRVO on TKIs received dexamethasone implant treatment and obtained a fluid-free macula. We would like to raise awareness among our colleague oncologists about the possibility of CRVO related to TKI use and the necessity for patients to be screened regularly by a retinal specialist.

Effect of Kinesio taping on edema and wrist functions in patients with distal radius fracture followed conservatively with a cast: A randomized controlled single-blinded study.

BACKGROUND: Data in the literature on the results of Kinesio taping (KT) application after cast removal in patients with distal radius fracture (DRF) are quite limited. PURPOSE: It was aimed to evaluate the effectiveness of KT applied immediately after cast removal in addition to the exercise program on edema, functionality, range of motion, and muscle strength in patients with conservatively followed DRF. STUDY DESIGN: Randomized controlled single-blinded clinical study. METHODS: This study was conducted with 64 patients with a diagnosis of DRF. The patients were randomized as Kinesio taping group (KTG) and control group. Both groups received a conventional home exercise program. KT was applied to patients in KTG for 10 days. Circumference and volume measurements were taken at baseline and day 10. Arm, Shoulder, and Hand Questionnaire for Disability, Visual Analog Scale, grip strength, and wrist joint range of motion measurements were taken at baseline, day 5, and day 10. RESULTS: The circumference difference between the affected extremity and the healthy extremity was statistically greater in the control group on the fifth day at the wrist level (<0.001) and 6 cm proximal to the wrist (p = 0.001). The circumference difference between the affected extremity and the healthy extremity was statistically greater in the control group on the 10th day at the wrist level (p < 0.05) and 6 cm proximal to the wrist (p = 0.01). Wrist extension angle (<0.001), wrist flexion angle (p = 0.001), and supination angle (p = 0.001) were higher in KTG on the 10th day. On the 10th day, the grip strength (p < 0.05) was higher in the KTG, while the Visual Analog Scale value (p < 0.01), Arm, Shoulder, and Hand Questionnaire for Disability score (p < 0.01), and the percentage of strength loss in the healthy arm (p < 0.01) were lower in the KTG. CONCLUSIONS: In patients with DRF who were treated conservatively with a cast, the inclusion of Kinesio taping (KT) in the rehabilitation program was found to be effective in reducing edema and pain, as well as improving functionality, strength, and range of motion.

Unmasking Negative Pressure Pulmonary Edema Following Hanging: A Case Series.

Pulmonary edema is a rare mechanism of death that develops after partial hanging, a potential complication that physicians should consider early in the management of these patients. This case series discusses the presentation, evaluation, and treatment course of three patients who had attempted suicide by hanging and were admitted to the hospital. These patients were admitted to the intensive care unit after being stabilized and supportive treatment was provided. In all the cases, a radiological scan of the chest revealed diffuse infiltrates consistent with pulmonary edema on both sides, features of which were also noted during a diagnostic bronchoscopy. After providing the best intensive care in the hospital, two patients clinically improved, and one patient succumbed to cardiac arrest. As most patients will be brought dead to the hospital following hanging, negative pressure pulmonary edema remains underdiagnosed. Thus, this case series enumerates the possible etiologies of negative pressure pulmonary edema and its contribution to death following suicidal hanging.

Boron neutron capture therapy as a larynx-preserving treatment for locally recurrent laryngeal carcinoma after conventional radiation therapy: A preliminary report.

OBJECTIVE: Laryngeal preservation and a radical cure are the treatment goals for laryngeal carcinoma, and larynx-preserving therapy is generally preferred for early-stage laryngeal carcinoma. When laryngeal carcinoma recurs locally, patients are often forced to undergo total laryngectomy, resulting in loss of vocal function. However, many patients with laryngeal carcinoma who have residual or recurrent disease after radiotherapy wish to preserve their voice. The purpose of this study was to investigate the possibility of using BNCT as a larynx-preserving treatment for residual or recurrent laryngeal carcinomas following radical irradiation. PATIENTS AND METHODS: This study included 15 patients who underwent BNCT for residual or recurrent laryngeal carcinoma after radical laryngeal carcinoma irradiation. The number of treatment sessions for all patients was one irradiation. Before BNCT, the recurrent laryngeal carcinoma stage was rT1aN0, rT2N0, rT2N1, rT3N0, rT3N1, and rT4aN0 in one, six, one, three, one, and three patients, respectively. The median maximum tumor diameter before BNCT was 15 mm (8-22 mm). All patients underwent a tracheostomy before BNCT to mitigate the risk of upper airway stenosis due to laryngeal edema after BNCT. Treatment efficacy was evaluated retrospectively using monthly laryngoscopy after BNCT and contrast-enhanced CT scans at 3 months. The safety of treatment was evaluated based on examination findings and interviews with patients. RESULTS: The median hospital stay after BNCT was 2 days (1-6). The response rate at three months after BNCT in 15 patients with locally recurrent laryngeal carcinoma was 93.3 %, and the CR rate was 73.3 %. The most frequent adverse event associated with BNCT was laryngeal edema, which occurred in nine patients the day after BNCT. The average course of laryngeal edema peaked on the second day after BNCT and almost recovered after 1 week in all patients. One patient had bilateral vocal fold movement disorders. None had dyspnea because of prophylactic tracheostomy. No grade four or higher adverse events occurred. Other grade 2 adverse events included pharyngeal mucositis, diarrhea, and sore throat. Three months after BNCT, tracheostomy tubes were removed in nine patients, retinal cannulas were placed in three patients, and voice cannulas were placed in three patients. CONCLUSIONS: BNCT for locally recurrent laryngeal carcinoma can safely deliver radical irradiation to tumor tissues, even in patients undergoing radical irradiation. BNCT has shown antitumor effects against recurrent laryngeal carcinoma. However, further long-term observations of the treatment outcomes are required.

Dystrophin 71 deficiency causes impaired aquaporin-4 polarization contributing to glymphatic dysfunction and brain edema in cerebral ischemia.

OBJECTIVE: The glymphatic system serves as a perivascular pathway that aids in clearing liquid and solute waste from the brain, thereby enhancing neurological function. Disorders in glymphatic drainage contribute to the development of vasogenic edema following cerebral ischemia, although the molecular mechanisms involved remain poorly understood. This study aims to determine whether a deficiency in dystrophin 71 (DP71) leads to aquaporin-4 (AQP4) depolarization, contributing to glymphatic dysfunction in cerebral ischemia and resulting in brain edema. METHODS: A mice model of middle cerebral artery occlusion and reperfusion was used. A fluorescence tracer was injected into the cortex and evaluated glymphatic clearance. To investigate the role of DP71 in maintaining AQP4 polarization, an adeno-associated virus with the astrocyte promoter was used to overexpress Dp71. The expression and distribution of DP71 and AQP4 were analyzed using immunoblotting, immunofluorescence, and co-immunoprecipitation techniques. The behavior ability of mice was evaluated by open field test. Open-access transcriptome sequencing data were used to analyze the functional changes of astrocytes after cerebral ischemia. MG132 was used to inhibit the ubiquitin-proteasome system. The ubiquitination of DP71 was detected by immunoblotting and co-immunoprecipitation. RESULTS: During the vasogenic edema stage following cerebral ischemia, a decline in the efflux of interstitial fluid tracer was observed. DP71 and AQP4 were co-localized and interacted with each other in the perivascular astrocyte endfeet. After cerebral ischemia, there was a notable reduction in DP71 protein expression, accompanied by AQP4 depolarization and proliferation of reactive astrocytes. Increased DP71 expression restored glymphatic drainage and reduced brain edema. AQP4 depolarization, reactive astrocyte proliferation, and the behavior of mice were improved. After cerebral ischemia, DP71 was degraded by ubiquitination, and MG132 inhibited the decrease of DP71 protein level. CONCLUSION: AQP4 depolarization after cerebral ischemia leads to glymphatic clearance disorder and aggravates cerebral edema. DP71 plays a pivotal role in regulating AQP4 polarization and consequently influences glymphatic function. Changes in DP71 expression are associated with the ubiquitin-proteasome system. This study offers a novel perspective on the pathogenesis of brain edema following cerebral ischemia.

Effect of ranibizumab combined with laser photocoagulation in the treatment of diabetic macular edema.

Objective: To explore the clinical effect of ranibizumab combined with laser photocoagulation (LP) in treating diabetic macular edema (DME). Methods: We retrospectively reviewed the clinical data of 118 patients with DME admitted to The Affiliated Eye Hospital of Nanchang University from May 2021 to March 2023. Among them, 38 patients received LP alone (Laser-group), 39 patients received ranibizumab alone (Ranibizumab-group), and 41 patients received LP combined with ranibizumab (Combined-group). The improvement of macular edema (ME), visual acuity, and complications between the groups were compared. Results: The time of ME regression, exudation absorption and fundus hemorrhage absorption in the Combined-group was shorter than in the Laser-group and the Ranibizumab-group (P<0.05). After treatment, the CMT and RNV of the three groups decreased compared to pretreatment levels and were lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). BCVA increased after the treatment in all groups, and was markedly higher in the Combined-group than in the Laser and the Ranibizumab-groups (P<0.05). NO were higher in the Combined-group compared to the Laser-group and the Ranibizumab-group. The post-treatment VEGF levels decreased in all groups, and were significantly lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). The incidence of complications in the Combined-group was lower than in the Laser-group and the Ranibizumab-group (P<0.05). Conclusions: Compared to ranibizumab or LP alone, ranibizumab combined with LP is more effective in reducing ME in patients with DEM, and is associated with fewer complications.

A Case of Postoperative Noncardiogenic Edema: Negative Pressure Pulmonary Edema.

A case of complete recovery of negative pressure pulmonary edema after a Cottle surgery in a 24-year-old male. Teaching point: Negative pressure pulmonary edema is an important cause of postoperative noncardiogenic edema, with the spontaneous disappearance of all complaints within a relatively short period.

A Superior Squeeze: Superior Vena Cava Syndrome Secondary to Small Cell Lung Cancer.

Superior vena cava (SVC) syndrome is an uncommon yet potentially fatal syndrome occurring after intrinsic or extrinsic compression to the SVC. While there are multiple emerging etiologies for this phenomenon, malignancy remains the most common. It is characterized by several symptoms including facial swelling, extremity swelling, shortness of breath, and headaches. We present the case of a 59-year-old female with a past medical history of cocaine abuse who was admitted for upper extremity swelling and facial edema. Imaging revealed a right suprahilar mass compressing a branch of the right pulmonary artery and SVC, in addition to bilateral segmental and subsegmental pulmonary emboli. She underwent an emergent biopsy and SVC stenting, with immunostaining revealing small cell lung cancer (SCLC). This case highlights a severe presentation of SVC syndrome caused by previously undetected SCLC.

An Unusual Presentation of Acute Severe Mitral Regurgitation.

Mitral regurgitation (MR) results from retrograde blood flow from the left ventricle to the left atrium. Common etiologies of acute severe MR include papillary muscle rupture from myocardial infarction, leaflet perforation in infective endocarditis, chordal rupture (pop) in myxomatous valve disease, acute rheumatic fever with carditis, or functional MR due to cardiomyopathies, myocarditis or Takotsubo cardiomyopathy. Here, we present an unusual case of acute severe MR due to ruptured chordae tendineae likely secondary to degenerative valve disease. A 59-year-old male with a past medical history of hypertension and renal calculi was evaluated in the outpatient office for a urologic procedure. He was sent to the emergency room with left-sided chest pain, 6/10 in intensity, burning in nature, and non-radiating with no aggravating and relieving factors. He had nausea and vomiting for the past three days. He reported similar chest pain at rest and on exertion multiple times over the past year. He also had a chronic cough with no recent changes. His examination was unremarkable. Chest X-ray showed interstitial lung markings. Electrocardiography revealed an old right bundle branch block, but no ST/T-wave changes. He was admitted and treated for atypical pneumonia with ceftriaxone and azithromycin. The following morning, he complained of persistent chest pain 9/10 in intensity which improved with nitroglycerin. His examination revealed a new onset holosystolic murmur heard over the precordium. A two-dimensional echocardiogram showed a preserved ejection fraction of 55-60%, severe MR with eccentric jet, concerning for partially flail leaflet of the mitral valve. He was transferred to the university hospital for mitral valve replacement. Patients with acute rupture of chordae tendineae usually progress to severe mitral valve regurgitation. These patients usually present with pulmonary edema, signs of heart failure, and cardiogenic shock. Papillary muscle dysfunction, as well as partial or complete rupture of the mitral chordae can be detected as a new-onset holosystolic murmur and can be a crucial sign for early recognition. In our case, the patient developed a new holosystolic murmur on day two of admission which was recognized early, and prompt surgical intervention was performed.

Thermal Pharyngeal Injury Resulting From Vaping: A Case Report.

Thermal injury to the pharyngeal structures is uncommon, and clinicians generally attribute these injuries to consuming hot foods or liquids. While thermal injuries have been reported with the ingestion of hot substances, thermal injuries from vape pens have not been widely described in the literature. We present a case of a 35-year-old male who presented to the emergency department (ED) with oropharyngeal burns after utilizing a vape pen that malfunctioned. The patient had visible burns on his uvula, as well as on the soft and hard palate. Additionally, he had symptoms of difficulty swallowing and a hoarse voice, which raised concerns about a possible deeper airway or lung injury. The patient required a flexible nasopharyngolaryngoscopy by a head and neck surgeon, which revealed mild edema and erythema of the epiglottis and the arytenoids. The patient was admitted to the hospital overnight for observation and treatment with analgesia and dexamethasone. The following morning, the patient's symptoms had improved. The repeat nasopharyngolaryngoscopy showed improvement in the swelling of the epiglottis and arytenoids, and the patient was deemed stable for discharge. This case brings attention to the variety of injuries possible from e-cigarette use and the importance of prompt management of oropharyngeal thermal injuries.

A health economic pilot study comparing two diabetic retinopathy screening strategies.

To compare two screening strategies for diabetic retinopathy (DR), and to determine the health-economic impact of including optical coherence tomography (OCT) in a regular DR screening. This cross-sectional study included a cohort of patients (≥ 18 years) with type 1 or 2 diabetes mellitus (T1D or T2D) from a pilot DR screening program at Oslo University Hospital, Norway. A combined screening strategy where OCT was performed in addition to fundus photography for all patients, was conducted on this cohort and compared to our existing sequential screening strategy. In the sequential screening strategy, OCT was performed on a separate day only if fundus photography indicated diabetic macular edema (DME). The presence of diabetic maculopathy on fundus photography and DME on OCT was determined by two medical retina specialists. Based on the prevalence rate of diabetic maculopathy and DME from the pilot, we determined the health-economic impact of the two screening strategies. The study included 180 eyes of 90 patients. Twenty-seven eyes of 18 patients had diabetic maculopathy, and of these, 7 eyes of 6 patients revealed DME on OCT. When diabetic maculopathy was absent on fundus photographs, OCT could not reveal DME. Accordingly, 18 patients (20%) with diabetic maculopathy would have needed an additional examination with OCT in the sequential screening strategy, 6 (33%) of whom would have had DME on OCT. In an extended healthcare perspective analysis, the cost of the sequential screening strategy was higher than the cost of the combined screening strategy. There was a weak association between diabetic maculopathy on fundus photography and DME on OCT. The health economic analysis suggests that including OCT as a standard test in DR screening could potentially be cost-saving.

[Aflibercept in a real-world setting: the AURIGA study : 24-month results of the German cohort of treatment-naïve patients with macular edema following retinal vein occlusion receiving intravitreal aflibercept]. / Aflibercept im klinischen Alltag: die AURIGA-Studie : 24-Monats-Ergebnisse der deutschen Kohorte behandlungsnaiver Patienten mit Makulaödem bei retinalem Venenverschluss unter Therapie mit intravitrealem Aflibercept.

BACKGROUND: AURIGA is the largest prospective real-world study to evaluate intravitreal aflibercept 2 mg (IVT-AFL) treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) and diabetic macular edema. Here we present the 24-month data from the German cohort of treatment-naïve patients with ME due to RVO. METHODS: Treatment-naïve patients with ME secondary to RVO were treated with IVT-AFL 2 mg in the routine clinical practice. The primary endpoint was mean change in visual acuity (VA, early treatment diabetic retinopathy, ETDRS, letters) at month 12 compared to baseline. Analyses were descriptive. RESULTS: Analysis included 130 patients with RVO (n = 61, 46.9% with central RVO, n = 69, 53.1% with branch RVO). The mean (± SD) time the RVO patients remained in the study was 18.4 ± 7.4 months. The mean VA gain (95% confidence interval) in the overall cohort was +10.9 (7.5-14.2) letters at month 12 and +9.7 (6.1-13.3) at month 24 (baseline VA 56.5 ± 18.9 letters). At 24 months, 67% of RVO patients gained ≥5 letters and 40% gained ≥15 letters. The mean number of injections was 4.4 ± 1.3 up to month 6, 6.2 ± 2.7 up to month 12 and 8.2 ± 4.5 up to month 24. The mean central retinal thickness (CRT) reduction was -206µm (-252 to -160µm) at 12 months and -219µm (-263 to -175µm) at 24 months (baseline CRT 507 ± 177 µm). The safety profile was consistent with that of previous studies. DISCUSSION: In the German AURIGA cohort of treatment-naïve patients with ME secondary to RVO, IVT-AFL 2 mg treatment in clinical practice resulted in rapid and clinically relevant VA gains and a reduction in CRT. These results were largely maintained over 24 months despite the low injection frequency from month 6.

Transient response to high-dose niacin therapy in a patient with NAXE deficiency.

Background: NAXE-encephalopathy or early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL-1) and NAXD-encephalopathy (PEBEL-2) have been described recently as mitochondrial disorders causing psychomotor regression, hypotonia, ataxia, quadriparesis, ophthalmoparesis, respiratory insufficiency, encephalopathy, and seizures with the onset being usually within the first three years of life. It usually leads to rapid disease progression and death in early childhood. Anecdotal reports suggest that niacin, through its role in nicotinamide adenine dinucleotinde (NAD) de novo synthesis, corrects biochemical derangement, and slows down disease progression. Reports so far have supported this observation. Methods: We describe a patient with a confirmed PEBEL-1 diagnosis and report his clinical response to niacin therapy. Moreover, we systematically searched the literature for PEBEL-1 and PEBEL-2 patients treated with niacin and details about response to treatment and clinical data were reviewed. Furthermore, we are describing off-label use of a COX2 inhibitor to treat niacin-related urticaria in NAXE-encephalopathy. Results: So far, seven patients with PEBEL-1 and PEBEL-2 treated with niacin were reported, and all patients showed a good response for therapy or stabilization of symptoms. We report a patient exhibiting PEBEL-1 with an unfavorable outcome despite showing initial stabilization and receiving the highest dose of niacin reported to date. Niacin therapy failed to halt disease progression or attain stabilization of the disease in this patient. Conclusion: Despite previous positive results for niacin supplementation in patients with PEBEL-1 and PEBEL-2, this is the first report of a patient with PEBEL-1 who deteriorated to fatal outcome despite being started on the highest dose of niacin therapy reported to date.

Aflibercept or ranibizumab for diabetic macular edema.

Background: Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME. Methods: This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography. Results: Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20-74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group. Conclusions: Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.

Nephrotic syndrome and adrenoleukodystrophy in a 5-year-old boy.

Nephrotic syndrome is a common condition characterized by filtration of large amounts of protein, hypoalbuminemia, reduced plasma oncotic pressure, sodium retention, and edema. The mechanism responsible for sodium retention in this condition is still controversial. Two different pathophysiological pathways have been proposed to explain edema formation: activation of neurohumoral effector mechanisms, including the renin-angiotensin-aldosterone system, or abnormal intrinsic/primary renal sodium retention. A 5-year-old boy with X-linked adrenoleukodystrophy presented with bilateral leg swelling, massive proteinuria, and hypoalbuminemia. Minimal change disease was diagnosed. The patient was initially treated with corticosteroids and experienced several relapses. The progression of fractional excretion of sodium correlated with proteinuria and undetectable aldosterone levels. This unusual finding suggests that the mechanism of tubular sodium avidity in this child with mineralocorticoid insufficiency was independent of the renin-angiotensin-aldosterone system.

Cardiovascular effects of breath-hold diving at altitude.

Hypoxia, centralization of blood in pulmonary vessels, and increased cardiac output during physical exertion are the pathogenetic pathways of acute pulmonary edema observed during exposure to extraordinary environments. This study aimed to evaluate the effects of breath-hold diving at altitude, which exposes simultaneously to several of the stimuli mentioned above. To this aim, 11 healthy male experienced divers (age 18-52y) were evaluated (by Doppler echocardiography, lung echography to evaluate ultrasound lung B-lines (BL), hemoglobin saturation, arterial blood pressure, fractional NO (Nitrous Oxide) exhalation in basal condition (altitude 300m asl), at altitude (2507m asl) and after breath-hold diving at altitude. A significant increase in E/e' ratio (a Doppler-echocardiographic index of left atrial pressure) was observed at altitude, with no further change after the diving session. The number of BL significantly increased after diving at altitude as compared to basal conditions. Finally, fractional exhaled nitrous oxide was significantly reduced by altitude; no further change was observed after diving. Our results suggest that exposure to hypoxia may increase left ventricular filling pressure and, in turn, pulmonary capillary pressure. Breath-hold diving at altitude may contribute to interstitial edema (as evaluated by BL score), possibly because of physical efforts made during a diving session. The reduction of exhaled nitrous oxide at altitude confirms previous reports of nitrous oxide reduction after repeated exposure to hypoxic stimuli. This finding should be further investigated since reduced nitrous oxide production in hypoxic conditions has been reported in subjects prone to high-altitude pulmonary edema.

Intravitreal Injection of Conbercept Combined with Dexamethasone for Macular Edema Following Central Retinal Vein Occlusion.

Background: To compare the efficacy of intravitreal injections of Conbercept combined with dexamethasone (DEX) for macular edema (ME) following central retinal vein occlusion (CRVO). Methods: This was a prospective, single-masked, randomised, controlled clinical trial. Patients with ME following CRVO were randomised into groups to receive intravitreal injections of 0.5 mg Conbercept plus 0.2 mg DEX or 0.5 mg Conbercept alone on day 0 followed by repeat injections as indicated. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to month 12. Secondary outcome measures included decrease in central retinal thickness (CRT), injection frequency and interval and percentage of patients who gained more than 15 ETDRS letters or achieved a CRT of < 250 µm at month 12. Results: 33 males (51%) and 32 females (49%) were initially recruited with an average age of 56.64 ± 13.88 years. Patients in the Conbercept and Conbercept + DEX groups gained an average of 14.55 ± 19.19 and 14.88 ± 17.68 ETDRS letters, respectively, at months 12 (t = 4.221, P = 0.000; and t = 4.834, P = 0.000) with no significant difference between the two groups (t = 0.071, P = 0.943). In the Conbercept group, the mean reduction in CRT from baseline to month 12 was 435.26 ± 293.37 µm (t = 8.261, P = 0.000) compared to 431.36 ± 294.55 (t = 8.413, P = 0.000) in the Conbercept + DEX group. There was no significant difference between the two groups (t = 0.053, P = 0.958). The Conbercept + DEX group received fewer intravitreal injections. No major complications occurred. Conclusion: Conbercept, alone or with DEX, can improve BCVA and reduce CRT in ME following CRVO without serious adverse events. The treatment interval was longer in the Conbercept + DEX group. Trial Registration: The study was registered with the Chinese Clinical Trial Registry at 5 July 2017. (http://www.chictr.org.cn, 05/07/2017 Registration Number: ChiCTR-INR-17011877).

The cornel Iridoid glycoside attenuated brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized aquaporin 4.

Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin.

Investigating the Therapeutic Effects of Nimodipine on Vasogenic Cerebral Edema and Blood-Brain Barrier Impairment in an Ischemic Stroke Rat Model.

Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-minute blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.