Should intravitreal dexamethasone implant in refractory diabetic macular edema be used as an adjuvant therapy or switch therapy?

ABSTRACT Purpose: To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab. Methods: This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up. Results: In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007). Conclusions: In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.

Screening of Sensorial and Inflammatory Changes in Patients Submitted to Orthognathic Surgery.

BACKGROUND: Despite the high levels of success after orthognathic surgery, the immediate postoperative pain and edema, besides the neurosensorial deficits, are common complications. OBJECTIVE: This study aimed to evaluate the pattern of sensory and inflammatory responses in patients undergoing orthognathic surgery. METHODS: This prospective observational study included 20 patients undergoing bimaxillary orthognathic surgery, who were evaluated in the preoperative period and on Days 1, 2, 3, 4, 5, 6, 7, and 30 after surgery, using a battery of tests to assess sensorial and inflammatory changes. RESULTS: Subjective and objective evaluations of edema indicated a trend toward edema resolution within 30 days, with a significant decrease in mouth opening on days 1, 7, and 30 after surgery. Regarding nasal obstruction, a significant increase in Nasal Obstruction Symptom Evaluation (NOSE) scores was demonstrated on the first, second, and third days, returning to preoperative levels after 30 days. There was a significant increase in visual analogic scale (VAS) scores from the first to the seventh day after surgery, with a reduction within 30 days. For mechanical and thermal sensitivity tests, the lower lip and chin regions had poorer results, without recovery after 30 days. Positive correlations were observed between painful and inflammatory parameters, as well as between subjective and objective evaluations. Analysis of saliva biomarkers did not show significant differences for pre- and postoperative CCL3 or CCL4 levels. CONCLUSION: Data provide new evidence about the early inflammatory and sensorial complications after orthognathic surgery.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema.

OBJECTIVE: To investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME). METHODS: Forty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 µm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity. RESULTS: One-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed. CONCLUSION: The SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME. CLINICAL TRIAL NUMBER (CAAE): 22969019.4.0000.5440.

Ibrutinib-Related Uveitis in Non-Hodgkin Lymphoma Patients: A Case Report and Literature Review.

PURPOSE: To report two cases of ibrutinib-related uveitis and review the literature to date. METHODS: We report two cases of ibrutinib-related uveitis using CARE guidelines and review the cases reported in the literature. RESULTS: Case 1) A 55-year-old female with recurrent primary central nervous system lymphoma presented with bilateral decreased visual acuity, photophobia, and floaters that started one month after initiating oral treatment with ibrutinib. Chronic non-granulomatous bilateral anterior-intermediate uveitis with macular edema was identified. Secondary causes were ruled out, and a presumptive diagnosis of ibrutinib-related uveitis was made. Case 2) A 57-year-old female with Waldenström macroglobulinemia who was treated with ibrutinib for two years presented with bilateral blurred vision, photophobia, red eyes, and floaters. A diagnosis of non-granulomatous, noninfectious panuveitis with bilateral cystoid macular edema was made. Secondary causes were ruled out, and ibrutinib toxicity was the most likely cause. CONCLUSION: Ibrutinib-related uveitis is a novel and under-diagnosed clinical entity. The most frequent clinical presentation in the literature is bilateral, non-granulomatous, anterior, and intermediate uveitis. Macular edema is a frequent complication. Uveitis usually requires topical treatment and the suspension of ibrutinib. Switching to second-generation Bruton tyrosine kinase inhibitors is proposed as a potential therapeutic alternative.

Acetylsalicylic acid and dihydroartemisinin combined therapy on experimental malaria-associated acute lung injury: analysis of lung function and the inflammatory process.

BACKGROUND: Severe malaria can cause respiratory symptoms, which may lead to malaria-acute lung injury (MA-ALI) due to inflammation and damage to the blood-gas barrier. Patients with severe malaria also often present thrombocytopenia, and the use of acetylsalicylic acid (ASA), a commonly used non-steroidal anti-inflammatory drug with immunomodulatory and antiplatelet effects, may pose a risk in regions where malaria is endemic. Thus, this study aimed to investigate the systemic impact of ASA and dihydroartemisinin (DHA) on ALI induced in mice by Plasmodium berghei NK65 (PbNK65). METHODS: C57BL/6 mice were randomly divided into control (C) and PbNK65 infected groups and were inoculated with uninfected or 104 infected erythrocytes, respectively. Then, the animals were treated with DHA (3 mg/kg) or vehicle (DMSO) at the 8-day post-infection (dpi) for 7 days and with ASA (100 mg/kg, single dose), and analyses were performed at 9 or 15 dpi. Lung mechanics were performed, and lungs were collected for oedema evaluation and histological analyses. RESULTS: PbNK65 infection led to lung oedema, as well as increased lung static elastance (Est, L), resistive (ΔP1, L) and viscoelastic (ΔP2, L) pressures, percentage of mononuclear cells, inflammatory infiltrate, hemorrhage, alveolar oedema, and alveolar thickening septum at 9 dpi. Mice that received DHA or DHA + ASA had an increase in Est, L, and CD36 expression on inflammatory monocytes and higher protein content on bronchoalveolar fluid (BALF). However, only the DHA-treated group presented a percentage of inflammatory monocytes similar to the control group and a decrease in ΔP1, L and ΔP2, L compared to Pb + DMSO. Also, combined treatment with DHA + ASA led to an impairment in diffuse alveolar damage score and lung function at 9 dpi. CONCLUSIONS: Therapy with ASA maintained lung morpho-functional impairment triggered by PbNK65 infection, leading to a large influx of inflammatory monocytes to the lung tissue. Based on its deleterious effects in experimental MA-ALI, ASA administration or its treatment maintenance might be carefully reconsidered and further investigated in human malaria cases.

Cardiac remodeling and inflammation detected by magnetic resonance imaging in COVID-19 survivors.

Background: Concerns have been raised about cardiac inflammation in patients with long COVID-19, particularly those with myocardial injury during the acute phase of the disease. This study was conducted to examine myopericardial involvement, detected by cardiac magnetic resonance (CMR) imaging in patients hospitalized for COVID-19. Methods: Adult patients hospitalized with COVID-19 who presented myocardial injury or increased D-dimers were enrolled in this prospective study. All patients were invited to undergo CMR imaging examination after discharge. During follow-up, patients with nonischemic myocardial or pericardial involvement detected on the first CMR imaging examination underwent second examinations. CMR imaging findings were compared with those of a control group of healthy patients with no comorbidity. Results: Of 180 included patients, 53 underwent CMR imaging examination. The mean age was 58.4 ± 18.3 years, and 73.6 % were male. Myocardial and pericardial LGE was reported in 43.4 % and 35.8 % of patients, respectively. Nonischemic myocardial or pericardial involvement was reported in 26 (49.1 %) patients. The prevalence of pericardial LGE was associated inversely with the interval between hospital discharge and CMR. COVID-19 survivors had higher end-systolic volume indices (ESVis) and lower left-ventricular ejection fractions than did healthy controls. Seventeen patients underwent follow-up CMR imaging; the end-diastolic volume index, ESVi, and prevalence of pericardial LGE, but not that of nonischemic LGE, were reduced. Conclusion: Among COVID-19 survivors with myocardial injury during the acute phase of the disease, the incidences of nonischemic myocardial and pericardial LGE and CMR imaging-detected signs of cardiac remodeling, partially reversed during follow-up, were high.

Biomechanical and tomographic findings in Brown-McLean syndrome.

Purpose: Brown-McLean syndrome (BMS) is a clinical condition characterized by peripheral corneal edema with central corneal transparency. This study aims to document the tomographic and biomechanical characteristics of 3 patients with typical BMS features using the Pentacam® AXL and CORVIS ST® (Oculus Optikgeräte GmbH, Wetzlar, Germany). Observations: Three cases of BMS are presented. Case 1 involves a 26-year-old male, Case 2 a 55-year-old male, and Case 3 a 74-year-old male. The patients in Cases 1 and 3 had bilateral BMS, while the patient in Case 2 had BMS in the right eye and aphakic bullous keratopathy in the left eye. All three patients were aphakic following cataract surgery. Notably, Cases 1 and 2 were first-degree relatives (son and father), both with bilateral microspherophakia and resultant bilateral aphakia from pediatric cataract surgery. Tomographic analysis revealed a consistent increase in corneal thickness from the center to the periphery in BMS eyes, marked by an abrupt rise in the corneal thickness spatial profile (CTSP) and percentage thickness increase (PTI) curves from the thinnest point towards the periphery. There was no loss of parallel isopachs, no displacement of the thinnest point of the cornea, and no evidence of focal posterior corneal surface depression, typical signs of generalized corneal edema. Biomechanically, BMS eyes exhibited relatively normal corneal stiffness, integrated radius, Ambrósio's relational thickness to the horizontal profile (ARTh), and maximum deformation amplitude ratio at 2mm from the corneal apex (DA ratio). However, the left eye of the patient in Case 2, which had aphakic bullous keratopathy, showed altered biomechanical parameters indicative of a softer cornea with loss of rigidity. Conclusions and importance: This case series is the first to evaluate the biomechanical and tomographic features of eyes with BMS. Despite the abrupt rise in CTSP and PTI curves from the thinnest point towards the periphery, the relatively normal central corneal biomechanical indices in these BMS eyes are expected when edema is limited to the periphery. These indices become abnormal when there is progression to central corneal edema with bullous keratopathy.

Intravitreal Antiangiogenic Treatment for Diabetic Retinopathy: A Mexican Real-Life Scenario Experience.

The objective of this study was to analyze the effectiveness of two intravitreal antiangiogenic drugs, ranibizumab and aflibercept, in a Mexican population over a period of 5 years, evaluating the improvement in visual acuity (VA) and central retinal thickness (CRT) in a real-world scenario. This is a retrospective study with subjects diagnosed with diabetic retinopathy (DR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME) receiving intravitreal injections of ranibizumab and/or aflibercept. In this study, we analyzed 588 eyes of 294 patients who received intravitreal antiangiogenic injections. The results showed an improvement regardless of antiangiogenic treatment or diagnosis in both VA and CRT. We found that both aflibercept and ranibizumab improved VA, while subjects with DME responded less to antiangiogenic treatment (p < 0.05), and that this difference did not correspond to the CRT measured by OCT. These results support evidence that intravitreal antiangiogenic medications are effective for ophthalmic complications of diabetes in our population; however, damage to visual structures is not reversed in most patients. And that the perception by the patient (VA) and that of the ophthalmologist (CRT) do not completely correlate in our study.

Efficacy of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Treating Traumatic Brain Injury-Induced Brain Edema: A Systematic Review and Meta-analysis of Animal Studies.

Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I2 = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1 h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.

Comparison of photobiomodulation with cryotherapy in the immediate postpartum period of parturients with grade I, grade II lacerations and/or episiotomy in reducing perineal and vulvar and edema: A randomized clinical trial.

INTRODUCTION: Vaginal delivery has several benefits for the parturient; however, during labor, some injuries, such as lacerations and/or episiotomy, can occur. Perineal pain may occur in the puerperium and can be aggravated in cases of perineal injury during childbirth, potentially impacting the physical and emotional aspects of the parturient. For this reason, it is necessary to use techniques that can relieve pain and edema in the immediate postpartum period, directly influencing recovery. OBJECTIVE: To compare the reduction of pain and improvement in healing using two techniques, namely photobiomodulation and cryotherapy, performed in the immediate postpartum period of up to 12 h, in parturients who suffered grade I and II lacerations and/or episiotomy. METHODS: Data collection was carried out through an evaluation questionnaire. Photobiomodulation was applied using the red and infrared laser from the DMC brand. The EVA and McGill scales were used for pain assessment, and the REEDA scale was used for the evaluation of edema and healing. RESULTS: The techniques were evaluated and applied to 56 patients, with 28 in each group (cryotherapy and LBI). Patients who received photobiomodulation showed superior improvement compared to cryotherapy. In the immediate postpartum period, there was a greater reduction in pain in favor of photobiomodulation (p = 0.008); and after 24 h, the difference was even more significant (p < 0.001).

The effect of kinesiotaping on edema: A systematic review and meta-analysis.

BACKGROUND: Treatment for edema involves multiple approaches, with Kinesiotaping having recently emerged as an option for edema reduction. OBJECTIVE: To systematically summarize current evidence on the effects of Kinesiotaping on edema reduction on any type of edema. METHODS: A systematic review was performed including randomized clinical trials that compared the effects of Kinesiotaping to any other intervention or no intervention on edema. Screening, assessment of methodological quality (PEDro scale) of studies, and confidence of evidence (GRADE) were analyzed by two independent reviewers. A quantitative summary is presented through meta-analyses. RESULTS: A total of 3750 studies were identified, of which 70 were included in this review, and were organized by body region (face, upper limbs and lower limbs) and by treatment time (short and long term). It was observed that Kinesiotaping was superior to comparison groups in the short-term for face edema (Standardized mean difference [SMD] -1.07; 95%CI -1.48 to -0.65) and lower limbs (SMD -0.55; 95%CI -1.06 to -0.05). Also, Kinesiotaping was superior to comparison group in the long-term for lower limbs (SMD -0.72; 95%CI -1.25 to -0.18). Kinesiotaping was not superior to the comparison groups for upper limbs in both the short (SMD -0.05; 95%CI -0.89 to 0.80) and long-term (SMD -0.04; 95%CI -0.31 to 0.24) protocols. CONCLUSION: Kinesiotaping seems to be an effective intervention to reduce acute edema around the face and potentially in the lower limbs in both short and long-term protocols, although the quality of evidence is very low. However, these positive results were not observed for the upper limbs.

Renal effects of selective cyclooxygenase-2 inhibitor anti-inflammatory drugs: A systematic review and meta-analysis.

Background: Selective cyclooxygenase-2 inhibitor anti-inflammatory drugs (coxibs) are associated with the development of adverse events, mainly gastrointestinal and cardiovascular, but renal effects are less known. Objective: To assess the renal risks of coxibs compared to placebo by means of a systematic review and meta-analysis. Methods: Randomized controlled trials that assessed renal effects of coxibs (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) were searched in PubMed, Embase, Scopus and other sources up to March 2024. Two independent reviewers performed study screening, data extraction, and risk of bias assessment. Random effect meta-analysis was employed to calculate the relative risks (RR) and 95% confidence intervals (CI) of renal effects of coxibs compared to placebo and inconsistency among studies (I 2 ). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Out of 5284 retrieved records, 49 studies (comprising 46 reports) were included. Coxibs increased the risk of edema (RR 1.46; 95% CI 1.15, 1.86; I 2  = 0%; 34 studies, 19,754 participants; moderate-certainty evidence), and celecoxib increased hypertensive or renal events (RR 1.24; 95% CI 1.08, 1.43; I 2  = 0%; 2 studies, 3589 participants; moderate-certainty evidence). Etoricoxib increased the risk of hypertension (RR 1.98; 95% CI 1.14, 3.46; I 2  = 34%; 13 studies, 6560 participants; moderate-certainty evidence); no difference was observed when pooling all coxibs (RR 1.26; 95% CI 0.91, 1.76; I 2  = 26%; 30 studies, 16,173 participants; moderate-certainty evidence). Conclusions: Coxibs likely increase the renal adverse effects, including hypertension and edema. Awareness about the renal risks of coxibs should be increased, mainly in high-risk patient.

Antivenom potential of the latex of Jatropha mutabilis baill. (Euphorbiaceae) against Tityus stigmurus venom: Evaluating its ability to neutralize toxins and local effects in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Species of the Jatropha genus (Euphorbiaceae) are used indiscriminately in traditional medicine to treat accidents involving venomous animals. Jatropha mutabilis Baill., popularly known as "pinhão-de-seda," is found in the semi-arid region of Northeastern Brazil. It is widely used as a vermifuge, depurative, laxative, and antivenom. AIM OF THE STUDY: Obtaining the phytochemical profile of the latex of Jatropha mutabilis (JmLa) and evaluate its acute oral toxicity and inhibitory effects against the venom of the scorpion Tityus stigmurus (TstiV). MATERIALS AND METHODS: The latex of J. mutabilis (JmLa) was obtained through in situ incisions in the stem and characterized using HPLC-ESI-QToF-MS. Acute oral toxicity was investigated in mice. The protein profile of T. stigmurus venom was obtained by electrophoresis. The ability of latex to interact with venom components (TstiV) was assessed using SDS-PAGE, UV-Vis scanning spectrum, and the neutralization of fibrinogenolytic and hyaluronidase activities. Additionally, the latex was evaluated in vivo for its ability to inhibit local edematogenic and nociceptive effects induced by the venom. RESULTS: The phytochemical profile of the latex revealed the presence of 75 compounds, including cyclic peptides, glycosides, phenolic compounds, alkaloids, coumarins, and terpenoids, among others. No signs of acute toxicity were observed at a dose of 2000 mg/kg (p.o.). The latex interacted with the protein profile of TstiV, inhibiting the venom's fibrinogenolytic and hyaluronidase activities by 100%. Additionally, the latex was able to mitigate local envenomation effects, reducing nociception by up to 56.5% and edema by up to 50% compared to the negative control group. CONCLUSIONS: The latex of Jatropha mutabilis exhibits a diverse phytochemical composition, containing numerous classes of metabolites. It does not present acute toxic effects in mice and has the ability to inhibit the enzymatic effects of Tityus stigmurus venom in vitro. Additionally, it reduces nociception and edema in vivo. These findings corroborate popular reports regarding the antivenom activity of this plant and indicate that the latex has potential for treating scorpionism.

Evaluation of the Humoral Response after Immunization with a Chimeric Subunit Vaccine against Shiga Toxin-Producing Escherichia coli in Pregnant Sows and Their Offspring.

Shiga toxin-producing Escherichia coli (STEC) poses a significant public health risk due to its zoonotic potential and association with severe human diseases, such as hemorrhagic colitis and hemolytic uremic syndrome. Ruminants are recognized as primary reservoirs for STEC, but swine also contribute to the epidemiology of this pathogen, highlighting the need for effective prevention strategies across species. Notably, a subgroup of STEC that produces Shiga toxin type 2e (Stx2e) causes edema disease (ED) in newborn piglets, economically affecting pig production. This study evaluates the immunogenicity of a chimeric protein-based vaccine candidate against STEC in pregnant sows and the subsequent transfer of immunity to their offspring. This vaccine candidate, which includes chimeric proteins displaying selected epitopes from the proteins Cah, OmpT, and Hes, was previously proven to be immunogenic in pregnant cows. Our analysis revealed a broad diversity of STEC serotypes within swine populations, with the cah and ompT genes being prevalent, validating them as suitable antigens for vaccine development. Although the hes gene was detected less frequently, the presence of at least one of these three genes in a significant proportion of STEC suggests the potential of this vaccine to target a wide range of strains. The vaccination of pregnant sows led to an increase in specific IgG and IgA antibodies against the chimeric proteins, indicating successful immunization. Additionally, our results demonstrated the effective passive transfer of maternal antibodies to piglets, providing them with immediate, albeit temporary, humoral immunity against STEC. These humoral responses demonstrate the immunogenicity of the vaccine candidate and are preliminary indicators of its potential efficacy. However, further research is needed to conclusively evaluate its impact on STEC colonization and shedding. This study highlights the potential of maternal vaccination to protect piglets from ED and contributes to the development of vaccination strategies to reduce the prevalence of STEC in various animal reservoirs.

Factors associated with clinical severity in chronic venous disease: The role of functional parameters.

INTRODUCTION: Chronic venous disease (CVD) is a highly prevalent disease that presents a wide spectrum of clinical expressions due to abnormalities in the venous system. Patients often have major functional changes that can limit daily activities. However, the functional factors associated with the severity of the disease remain poorly understood. OBJECTIVE: To identify the functional factors associated with CVD severity. METHODS: Seventy-five patients with CVD (92.0% females, 49.6 ± 13.3 years) were evaluated through clinical examination, lower limb perimetry, ankle range of motion (AROM), and lower limb muscle strength by the Heel Rise test, and Sit-to-stand test. Patients were stratified according to the disease severity as mild (telangiectasia, varicose veins, or edema in the lower limbs) or severe CVD (trophic changes or venous ulcer). RESULTS: Patients with severe CVD (n = 13) were older (p = 0.002), predominantly male (p = 0.007), with reduced AROM in dorsiflexion (p = 0.028) and inversion (p = 0.009), reduced lower limb strength by the Heel Rise test (p = 0.040), and greater circumference of the calf (p = 0.020), ankle (p = 0.003), and plantar arch (p = 0.041) when compared to mild CVD (n = 62). Advanced age, male sex, lower ankle range of motion in dorsiflexion, and greater ankle and plantar arch circumferences were associated with CVD severity. However, the ankle circumference (OR 1.258, 95% CI: 1.008-1.570; p = 0.042), together with advanced age and male sex, was the only functional variable that remained independently associated with CVD severity. CONCLUSION: The increased ankle circumference was a determinant of the CVD severity and may assist in risk stratification and guide treatment goals in this population.

Effect of kinesio tape application on the lymphatic system during knee arthroscopy surgery

Introduction: To control edema, physical therapy employs several techniques, such as elastic bandages application - Kinesio tape (KT) - to block or drain subcutaneous body fluids, due to the secondary effects of its elastic properties. Objective: To evaluate the effect kinesio tape application on the lymphatic system during knee arthroscopy surgery. Methods: Controlled clinical trial, with 28 patients, alternately divided into two groups (intervention and control) referred to arthroscopic surgical treatment of anterior cruciate ligament and meniscus injuries. Patients were evaluated in the preoperative and, on the 1st postoperative day, while the intervention group received KT application for the lymphatic system in the intraoperative period. Results: The intervention group showed statistically significant results in the non-formation of edema, according to perimetric (Point 2: p=0.010, Point 3: p≤0.001 and Point 4: p≤0.001) and ultrasound (p=0.007) analyses when compared to the control group. On the other hand, pain (p=0.056) did not present a significant difference, but in the intragroup comparison pre and postoperative, a considerable reduction (p=0.002) was observed. Conclusion: KT application for the lymphatic system in the intraoperative period of knee arthroscopy effectively minimized edema formation and reduced pain.

Beyond VEGF: Angiopoietin-Tie Signaling Pathway in Diabetic Retinopathy.

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

Peripheral inflammatory hyperalgesia is exacerbated in rats with metabolic disorders induced by a fructose diet.

This study explored the effects of fructose-induced obesity and metabolic disorders on peripheral inflammatory hyperalgesia, employing quantitative sensory testing with the von Frey test and measuring paw edema to assess inflammatory responses. Wistar rats were administered water or 10% fructose solution ad libitum over a period of 5 weeks. After intraplantar administration of inflammatory agents such as carrageenan (1 mg/paw), lipopolysaccharide (LPS; 100 µg/paw), or prostaglandin E2 (PGE2, 100 ng/paw), we conducted mechanical hyperalgesia tests and paw edema evaluations. The fructose diet resulted in dyslipidemia, elevated insulin and leptin plasma levels, insulin resistance, and increased epididymal and retroperitoneal adiposity compared to control animals. In response to inflammatory agents, the fructose group displayed significantly enhanced peripheral hyperalgesia and more pronounced paw edema. Our results demonstrate that fructose not only contributes to the development of obesity and metabolic disorder but also exacerbates peripheral inflammatory pain responses by enhancing prostaglandin sensitivity.

Acute Coronary Syndrome at Altitude: Diagnostic Dilemma on Aconcagua Using Point-of-Care Ultrasound.

At the Plaza de Mulas medical tent, located at 4300 m (14,100 ft) along the Normal Route to the 6960 m (22,837 ft) summit of Aconcagua in Argentina, a Korean male in his 50s with no known medical conditions presented with lightheadedness and shortness of breath. He had taken sildenafil and acetazolamide that morning without improvement. Vital signs on arrival were notable for oxygen saturations in the high 60s with basilar crackles on lung auscultation, concerning for high altitude pulmonary edema. The patient was started on oxygen via nasal cannula and given dexamethasone. History was limited secondary to language barriers, but on review of systems the patient noted mild chest pressure. Bedside cardiac echocardiogram was performed, which revealed a septal wall motion abnormality. The patient was therefore given aspirin and clopidogrel and was flown to a lower trailhead, where he was met by local Emergency Medical Services. A 12-lead electrocardiogram revealed an anterior ST-elevation myocardial infarction, and the patient was taken emergently to the catheterization lab in Mendoza and underwent stent placement with a full recovery.

Successful management of pulmonary edema secondary to accidental electrocution in a young dog.

BACKGROUND: Human records describe pulmonary edema as a life-threatening complication of electric shock. Successful management requires prompt recognition and intensive care. However, in companion animals, electrocutions are rarely reported, even though domestic environments are full of electrical devices and there is always the possibility of accidental injury. Therefore, it is important for veterinarians to know more about this condition in order to achieve successful patient outcomes. CASE PRESENTATION: A 3-month-old male Labrador Retriever was presented with a history of transient loss of consciousness after chewing on a household electrical cord. On admission, the puppy showed an orthopneic position with moderate respiratory distress. Supplemental oxygen via nasal catheter was provided, but the patient showed marked worsening of respiratory status. Point-of-care ultrasound exams suggested neurogenic pulmonary edema due to electrical shock close to the central nervous system and increased B-lines without evidence of cardiac abnormalities. Mechanical ventilation of the patient was initiated using volume-controlled mode with a tidal volume of 9 to 15 ml/kg until reaching an end-tidal carbon dioxide ≤ 40 mm Hg, followed by a stepwise lung-recruitment maneuver in pressure-controlled mode with increases of the peak inspiratory pressure (15 to 20 cm H2O) and positive end-expiratory pressure (3 to 10 cm H2O) for 30 min, and return to volume-controlled mode with a tidal volume of 15 ml/kg until reaching a peripheral oxygen saturation ≥ 96%. Weaning from the ventilator was achieved in six hours, and the patient was discharged two days after admission without neurological or respiratory deficits. CONCLUSIONS: We present a rather unusual case of a neurogenic pulmonary edema subsequent to accidental electrocution in a dog. Timely diagnosis by ultrasound and mechanical ventilation settings are described. Our case highlights that pulmonary edema should be considered a potentially life-threatening complication of electrical shock in small animal emergency and critical care medicine.