Gene therapy by virus-like self-spooling toroidal DNA condensates for revascularization of hindlimb ischemia.

Peripheral arterial diseases (PAD) have been reported to be the leading cause for limb amputations, and the current therapeutic strategies including antiplatelet medication or intervene surgery are reported to not clinically benefit the patients with high-grade PAD. To this respect, revascularization based on angiogenetic vascular endothelial growth factor (VEGF) gene therapy was attempted for the potential treatment of critical PAD. Aiming for transcellular delivery of VEGF-encoding plasmid DNA (pDNA), we proposed to elaborate intriguing virus-like DNA condensates, wherein the supercoiled rigid micrometer-scaled plasmid DNA (pDNA) could be regulated in an orderly fashion into well-defined nano-toroids by following a self-spooling process with the aid of cationic block copolymer poly(ethylene glycol)-polylysine at an extraordinary ionic strength (NaCl: 600 mM). Moreover, reversible disulfide crosslinking was proposed between the polylysine segments with the aim of stabilizing these intriguing toroidal condensates. Pertaining to the critical hindlimb ischemia, our proposed toroidal VEGF-encoding pDNA condensates demonstrated high levels of VEGF expression at the dosage sites, which consequently contributed to the neo-vasculature (the particularly abundant formation of micro-vessels in the injected hindlimb), preventing the hindlimb ischemia from causing necrosis at the extremities. Moreover, excellent safety profiles have been demonstrated by our proposed toroidal condensates, as opposed to the apparent immunogenicity of the naked pDNA. Hence, our proposed virus-like DNA condensates herald potentials as gene therapy platform in persistent expressions of the therapeutic proteins, and might consequently be highlighted in the management of a variety of intractable diseases.

Treatment Regimens of Neovascular Form of Age-Related Macular Degeneration. A Review.

This article presents an overview of treatment regimens of drugs containing antivascular endothelial growth factor for the treatment of neovascular form of age-related macular degeneration. Currently, drugs containing antivascular endothelial growth factor are the only effective treatment for this chronic and progressive disease. The treatment regimens for this disease in the last two decades have seen a shift from a simple endeavor to stabilize the disease to achieving maximum improvement of visual acuity and its maintenance, with improvement of the patient's quality of life and a minimal treatment burden on patients and their families. Other goals of the alternative dosing regimens that have replaced the original fixed regimens were greater individualization of the dosing regimen, better patient cooperation, saving financial costs and reducing the burden on application centers. Age-related macular degeneration, whether dry form or wet form, represents a serious health and socioeconomic problem, as the disease is one of the most common causes of severe and irreversible central visual acuity disorders up to the degree of practical blindness of one or both eyes in people over 50 years of age in developed industrialized countries. The most important issue is to ensure early diagnosis of this disease, followed by prompt and continuous treatment with an individualized proactive treatment regimen, with the aim of stabilizing and improving anatomical and functional results.

The relationship between the secondary vascular system and the lymphatic vascular system in fish.

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. However, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems among different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered. The most common interpretation assumes a similar dual setup of the vasculature in zebrafish and mammals: a cardiovascular circulatory system, and a lymphatic vascular system (LVS), in which the unidirectional flow is derived from surplus interstitial fluid and returned into the cardiovascular system. A competing interpretation questions the identity of the lymphatic vessels in fish as at least some of them receive their flow from arteries via specialised anastomoses, neither requiring an interstitial source for the lymphatic flow nor stipulating unidirectionality. In this alternative view, the 'fish lymphatics' are a specialised subcompartment of the cardiovascular system, called the secondary vascular system (SVS). Many of the contradictions found in the literature appear to stem from the fact that the SVS develops in part or completely from an embryonic LVS by transdifferentiation. Future research needs to establish the extent of embryonic transdifferentiation of lymphatics into SVS blood vessels. Similarly, more insight is needed into the molecular regulation of vascular development in fish. Most fish possess more than the five vascular endothelial growth factor (VEGF) genes and three VEGF receptor genes that we know from mice or humans, and the relative tolerance of fish to whole-genome and gene duplications could underlie the evolutionary diversification of the vasculature. This review discusses the key elements of the fish lymphatics versus the SVS and attempts to draw a picture coherent with the existing data, including phylogenetic knowledge.

Wound Modulations in Glaucoma Surgery: A Systematic Review.

Excessive fibrosis and resultant poor control of intraocular pressure (IOP) reduce the efficacy of glaucoma surgeries. Historically, corticosteroids and anti-fibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), have been used to mitigate post-surgical fibrosis, but these have unpredictable outcomes. Therefore, there is a need to develop novel treatments which provide increased effectiveness and specificity. This review aims to provide insight into the pathophysiology behind wound healing in glaucoma surgery, as well as the current and promising future wound healing agents that are less toxic and may provide better IOP control.

Association of Four VEGFA Gene Variants with Rheumatoid Arthritis Risk: A Meta-analysis and Trial Sequential Analysis.

The association between rheumatoid arthritis (RA) risk and specific variants of the Vascular Endothelial Growth Factor A (VEGFA) gene remains contentious. This study sought to elucidate the correlations between RA risk and several VEGFA gene variants, including VEGFA-634 (rs2010963), VEGFA-C936 (rs3025039), VEGFA-2578 (rs699947), VEGFA-1154 (rs1570360), through a comprehensive meta-analysis. We systematically reviewed literature from the Cochrane Library database, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and the Wanfang Data Information Service platform to gather relevant case-control studies. Using odds ratio (OR) and 95% confidence interval (95% CI), we analyzed the data to assess potential correlations. Sensitivity analysis and the Egger's test were employed to ensure the results stability and to evaluate potential publication bias. Additionally, trial sequential analysis (TSA) was conducted to validate the findings. Our meta-analysis incorporated ten studies involving 2817 patients and 2855 controls. Results indicated that the AA genotype of VEGFA-1154 (rs1570360) is associated with a reduced risk of RA in the overall population (AG + GG vs AA: P = 0.032 OR = 1.932 95% CI 1.059-3.523). However, no significant association is found for VEGFA-634 (rs2010963), VEGFA-C936 (rs3025039), and VEGFA-2578 (rs699947) variants with RA risk. Subgroup analysis revealed a significant association between the VEGF rs3025039(C936) variant and RA risk in the PCR-RFLP group under the TC vs. CC model. TSA confirmed the sufficiency of the sample size for robust conclusions. These findings suggest that the G allele of VEGFA-1154 (rs1570360) may increase RA risk, whereas the A allele appears to confer a protective effect. This study enhances our understanding of the genetic predispositions to RA and underscores the potential role of VEGFA gene variants in its pathogenesis.

Effects of slit lamp-delivered retinal laser photobiomodulation in a rat model of choroidal neovascularization.

Neovascular age-related macular degeneration, also known as exudative or wet age-related macular degeneration, is the leading cause of blindness in the developed world. Photobiomodulation has the potential to target the up-stream hypoxic and pro-inflammatory drivers of choroidal neovascularization. This study investigated whether photobiomodulation attenuates characteristic pathological features of choroidal neovascularization in a rodent model. Experimental choroidal neovascularization was induced in Brown Norway rats with laser photocoagulation. A custom-designed, slit-lamp-mounted, 670 nm laser was used to administer retinal photobiomodulation every 3 days, beginning 6 days prior to choroidal neovascularization induction and continuing until the animals were killed 14 days later. The effect of photobiomodulation on the size of choroidal neovascular membranes was determined using isolectin-B4 immunohistochemistry and spectral domain-optical coherence tomography. Vascular leakage was determined with fluorescein angiography. The effect of treatment on levels of vascular endothelial growth factor expression was quantified with enzyme-linked immunosorbent assay. Treatment with photobiomodulation was associated with choroidal neovascular membranes that were smaller, had less fluorescein leakage, and a diminished presence of inflammatory cells as compared to sham eyes. These effects were not associated with a statistically significant difference in the level of vascular endothelial growth factor when compared to sham eyes. The data shown herein indicate that photobiomodulation attenuates pathological features of choroidal neovascularization in a rodent model by mechanisms that may be independent of vascular endothelial growth factor.

Impact of Coronavirus Disease 2019 on Intravitreal Antivascular Endothelial Growth Factor Injection Rates in Nigerians.

Aim: To quantify the impact of coronavirus disease 2019 (COVID-19) on the rate of intravitreal antivascular endothelial growth factor (VEGF) injections (IVI) in eye hospitals in Nigeria. Materials and Methods: A retrospective, observational, comparative study. The IVIs given 12 months before (pre-COVID) and 12 months after the first announcement of the COVID-19 lockdown (COVID) in Nigeria in four hospitals were used as the sample for this study. All eyes were treatment naïve. We determined the total number of all anti-VEGF injections, the number given for each indication, and the number of each type of the three anti-VEGFs given. A comparison of the presenting vision in IVI eyes between the two eras and the visual outcome of the IVI treatment was made. Data were analyzed using the SPSS version 22 to determine statistical significance. Results: Male/female ratio, pre-COVID 63.4%/36.6% and COVID 58.6%/41.4% (P = 0.123). Age, pre-COVID 61.3 (SD 12.9) 9-95 years and COVID 57.5 (SD 16.4) 0.15-95 years. There was a 15.3% (81 eyes) reduction in the number of eyes between pre-COVID and COVID eras (528 and 447 eyes, respectively). Likewise, the number of IVIs reduced by 26% (221 IVIs) from 850 pre-COVID to 629 COVID, P = 0.005. A comparison of the proportion of eyes in the four clinic locations between the two eras was not statistically significant (P = 0.148). The commonest indication was proliferative diabetic retinopathy in both eras, 208 versus 178 eyes (323 versus 226 IVIs). Bevacizumab, Ranibizumab, and Aflibercept were given in the following proportions 60.2%, 22.3%, and 17.4% (pre-COVID) versus 60.2%, 31.5%, and 8.3% (COVID), P = 0.000. Presenting visual acuity was >6/60 in 67.4% of eyes (pre-COVID) versus 59.4% of eyes (COVID), P = 0.039. Vision improved in 51.3% of eyes (pre-COVID) versus 47.7% (COVID); there was no significant difference in visual outcome comparing both eras, P = 0.972. Conclusion: COVID-19 significantly reduced the number of eyes and IVIs. Eyes had worse presenting visual acuity during the COVID era; however, treatment outcome was comparable between COVID and pre-COVID eras.

Clinicopathological and immunohistochemical characteristics of bullous pilomatricoma: a retrospective, single-center study, and comparison with ordinary pilomatricoma.

BACKGROUND: Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. OBJECTIVES: This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. METHODS: The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. RESULTS: Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. STUDY LIMITATIONS: The study was retrospective, and the sample size was small. CONCLUSION: The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

Two-Year Follow-Up Study of Patients with Neovascular Age-Related Macular Degeneration Undergoing Anti-VEGF Treatment during the COVID-19 Pandemic.

BACKGROUND: regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate disease progression. METHODS: we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This study was conducted during the coronavirus disease 2019 (COVID-19) pandemic with a 2-year follow-up period. The best-corrected visual acuity (BCVA) and anatomical findings were evaluated before the pandemic, during the pandemic, and at 6-, 12-, 18-, and 24-months post-pandemic. RESULTS: The delayed and on-time groups comprised 54 and 72 patients, respectively. After the pandemic, the injection interval increased by 0.65 ± 1.51 months (p = 0.003), with 22.2% of the patients in the delayed group switching to the treat-and-extended regimen (p < 0.001). The delayed group showed greater mean BCVA deterioration (p = 0.027) and central subfield thickness (p = 0.037) at 6 months and worse maximum subretinal fluid height (p = 0.022) at 18 months than the on-time group. No difference was observed between the groups in the second year. CONCLUSION: the negative effects of delaying anti-VEGF treatment because of the COVID-19 pandemic can be ameliorated by changing the treatment regimen and shortening treatment intervals.

Comparison of pigment epithelium detachment composition indices between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months. METHODS: This was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F). RESULTS: A total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = - 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = - 0.53; p < 0.001 and PCV, r = - 0.09; p = 0.58). CONCLUSION: PEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months.

Nonsynonymous mutations in VEGF receptor binding domain alter the efficacy of bevacizumab treatment.

Vascular endothelial growth factor (VEGF) mediated angiogenesis is crucial for tumor progression. Isoforms of VEGF bind to different VEGF receptors (VEGFRs) to initiate angiogenesis specific cellular signaling. Inhibitors that target both the receptors and ligands are in clinical use to impede angiogenesis. Bevacizumab, a monoclonal antibody (mAb) approved by the Food and Drug Administration (FDA), binds in the VEGF receptor binding domain (RBD) of all soluble isoforms of VEGF and inhibits the VEGF-VEGFR interaction. Bevacizumab is also used in combination with other chemotherapeutic agents for a better therapeutic outcome. Understanding the intricate polymorphic character of VEGFA gene and the influence of missense or nonsynonymous mutations in the form of nonsynonymous polymorphisms (nsSNPs) on RBD of VEGF may aid in increasing the efficacy of this drug. This study has identified 18 potential nsSNPs in VEGFA gene that affect the VEGF RBD structure and alter its binding pattern to bevacizumab. The mutated RBDs, modeled using trRosetta, in addition to the changed pattern of secondary structure, post translational modification and stability compared to the wild type, have shown contrasting binding affinity and molecular interaction pattern with bevacizumab. Molecular docking analysis by ClusPro and visualization using PyMol and PDBsum tools have detected 17 nsSNPs with decreased binding affinity to bevacizumab and therefore may impact the treatment efficacy. Whereas VEGF RBD expressed due to rs1267535717 (R229H) nsSNP of VEGFA has increased affinity to the mAb. This study suggests that genetic characterization of VEGFA before bevacizumab mediated cancer treatment is essential in predicting the appropriate efficacy of the drug, as the treatment efficiency may vary at individual level.

Clinicopathological and immunohistochemical characteristics of bullous pilomatricoma: a retrospective, single-center study, and comparison with ordinary pilomatricoma

Abstract Background Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. Objectives This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. Methods The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. Results Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. Study limitations The study was retrospective, and the sample size was small. Conclusion The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

New immunological aspects of peri-implantitis

ABSTRACT Objective: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. Methods: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. Results: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. Conclusion: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis.

Cardiovascular Toxicity of Angiogenesis Inhibitors Among Patients With Cancer in Taiwan: A Nested Case-Control Study.

BACKGROUND: Research on the cardiovascular toxicity of angiogenesis inhibitors among patients with cancer in Taiwan is lacking. This observational study explored the risk of major adverse cardiovascular events (MACEs) associated with angiogenesis inhibitors in Taiwan. METHODS AND RESULTS: We conducted a nested case-control study using the TCR (Taiwan Cancer Registry) linked with the Taiwan National Insurance Claim Database. We matched every case with 4 controls using risk-set sampling by index date, age, sex, cancer type, and cancer diagnosis date. Conditional logistic regression was used to evaluate the risks of MACEs and different cardiovascular events using propensity score adjustment or matching. Sensitivity analyses were used to evaluate the risks matched by cancer stages or exposure within 1 year. Among a cohort of 284 292 after the exclusion of prevalent cases, the incidences of MACEs among the overall cohort and those exposed to angiogenesis inhibitors were 22.5 and 32.5 events per 1000 person-years, respectively. We matched 17 817 cases with 70 740 controls, with a mean age of 74.9 years, and 56.8% of patients were men. After propensity score adjustment, angiogenesis inhibitors were associated with increased risks of MACEs (odds ratio, 4.56; 95% CI, 1.78-11.59). Significantly increased risks were noted for heart failure hospitalization, myocardial infarction, cerebrovascular accident, and venous thromboembolism, but not for new-onset atrial fibrillation. Similar results were observed after matching by cancer stage or restriction of 1-year exposure. CONCLUSIONS: Angiogenesis inhibitors were associated with increased risks of MACEs among patients with various malignancies in Taiwan but were not associated with new-onset atrial fibrillation.

Relación del tratamiento y coste con la ganancia de agudeza visual en la degeneración macular asociada a la edad / Relationship between treatment and cost with visual acuity improvement in age-related macular degeneration

Fundamento. Relacionar la ganancia de agudeza visual (AV) con el coste asistencial y de tratamiento con terapia anti-factor de cre-cimiento endotelial vascular (antiVEGF) en pacientes diagnostica-dos de degeneración macular asociada a la edad exudativa (DMAE exudativa).Pacientes y métodos. Estudio observacional, longitudinal, retros-pectivo, de pacientes ≥50 años diagnosticados de DMAE exudativa, con AV logMAR entre 0,6 y 0,06, en seguimiento y tratamiento en nuestro hospital de tercer nivel entre el 01/01/2014 y el 31/12/2018.Resultados. Se incluyeron 778 pacientes, 62,2% mujeres y media de edad 79,83±7,94 años, con 957 ojos con DMAE exudativa. La AV final global (0,65±0,45) aumentó un 3,2% respecto de la inicial. El 60,3% de los ojos recibieron antiVEGF con ranibizumab, el 10,2% con aflibercept y el 29,5% con ambos (mixto). El grupo mixto in-crementó significativamente la AV respecto de la inicial, sin dife-rencias entre grupos. Aunque el seguimiento/tratamiento fue más largo para el grupo mixto, este recibió menos inyecciones antiVE-GF y tomografías de coherencia óptica (OCT). El gasto total por año y ojo tratado fue de 1.972,7 €±824,5; los costes fueron mayores para visita, OCT y tratamiento en el grupo de aflibercept, y menores para angiografías con fluoresceína, tratamiento antiVEGF y costes totales en el grupo mixto. La ganancia decimal de AV tuvo un coste de 872 €±1.077,7 sin diferencias significativas entre grupos.Conclusiones. Los tratamientos antiVEGF con ranibizumab, afli-bercept y ambos mantuvieron la AV en pacientes con DMAE exu-dativa. En general, los costes asistenciales y de tratamiento fueron menores en el grupo que recibió ambos fármacos (AU)

Background. We examined the relationship between visual acuity changes (VA) and the cost of care and treatment with anti-vascular endothelial growth factors (antiVEGF) in patients diagnosed with age-related exudative macular degeneration(exudative AMD).Methods. Observational, longitudinal, retrospective study of pa-tients ≥50 years of age diagnosed with exudative AMD, with a log-MAR VA between 0.6 and 0.06. and 0.06. Follow-up and treatment were done in our tertiary hospital between January 1, 2014 and December 31, 2018.Results. The study included 778 patients; 62.2% female and mean age 79.83±7.94 years; 957 eyes had exudative AMD. Mean of final VA (0.65±0.45) increasing 3.2% compared to initial values. Ranibi-zumab was administered to 60.3% of the eyes, aflibercept to 10.2% and ranibizumab + aflibercept (mixed group) to 29.5%. Significant increase in VA was seen in the group with the mixed treatment, with no inter-group differences. Although follow-up/treatment was longer for the mixed group, they received fewer anti-VEGF injections and optical coherence tomography (OCT). The total expenditure per year and treated eye was €1,972.7±824.5; costs were higher for visit, OCT, and treatment in the aflibercept group, and lower for fluorescein angiography, antiVEGF treatment, and total costs in the mixed group. Decimal VA gain had a cost of €872±1,077.7 with no significant inter-group differences.Conclusion. AntiVEGF treatments (ranibizumab, aflibercept, or both) maintained VA in patients with exudative AMD. Overall, care and treatment costs were lower in the group that received both drugs (AU)

Pierre-Marie Bamberger Syndrome Leading to the Diagnosis and Surgical Treatment of a Localized Lung Cancer.

Hypertrophic osteoarthropathy (HOA), manifested with digital clubbing, tubular bone periostosis, and large joint synovial effusions, exists in two forms: primary, which is the rarest form, and secondary. The latter is frequently associated with lung diseases and, in some cases, with non-small cell lung cancer (NSCLC) and is thus expressed in the form of a paraneoplastic syndrome. We report the case of a male smoker who was presented with secondary hypertrophic osteoarthropathy and was subsequently diagnosed with primary adenocarcinoma of the lung. A 63-year-old male with a history of ischemic heart disease and heavy tobacco consumption (60 pack-years) presented with painful osteoarthritis of all four extremities. A chest computed tomography (CT), a positron emission tomography (PET) scan, and a bronchoscopy revealed a 9 cm mass within the right lower lobe without mediastinal adenopathy. Bilateral lower limb X-rays revealed osteoarthropathy of the tibia. A right lower lobectomy and mediastinal lymph node dissection were performed. Final histopathology analysis reported an advanced mixed pulmonary adenocarcinoma. The postoperative course was uneventful and the patient was discharged on postoperative day 6. This report has highlighted the importance of clinical awareness of the association between HOA and carcinoma of the lung.

Non-steroidal intravitreal injection for noninfectious uveitic cystoid macular edema: Systematic review and meta-analysis.

PURPOSE: To systematically review the published manuscripts on the non-steroidal intravitreal injection for treatment of noninfectious uveitic cystoid macular edema (CME). METHODS: The PubMed, Scopus, and Web of Science, Science Direct, ProQuest, Cochrane Library, ProQuest, Embase, Clinical Key, and Springer were searched for relevant articles published until May 2022. The random-effects models were used to estimate the mean difference (MD) and 95% confidence interval (CI) for postoperative central macular thickness (CMT) and visual acuity (VA) changes. VA was transformed into the logarithm of the minimum angle of resolution (LogMAR). Meta-regression was conducted for adjusting the effects of potential confounders. RESULTS: A total of 17 relevant studies (258 eyes) were included in this meta-analysis. A significant improvement was observed in CMT in the last follow up (350.89 ± 108.43) compared to the baseline (452.3 ± 112.67) (Log MD = 1.82, 95% CI = 1.62, 2.02; I2 = 57.7%; P = 0.002). Additionally, VA also significantly improved in the last follow up (0.56 ± 0.29) compared to the baseline (0.75 ± 0.3) (Exponential MD = 0.82, 95% CI = 0.69, 0.95; I2 = 0.0%; P = 0.98). The subgroups analyzed included ten studies on anti-vascular endothelial growth factors (VEGF), three studies on infliximab, two studies on methotrexate (MTX), and two studies on diclofenac. All subgroups showed a significant improvement in both CMT and VA at the last follow-up (P < 0.05). CONCLUSION: Non-steroidal intravitreal injection including bevacizumab, ranibizumab, infliximab, MTX and diclofenac appears to be an effective treatment option for noninfectious uveitic CME.

Adjunctive effect of collagen membrane coverage to L-PRF in the treatment of periodontal intrabony defects: a randomized controlled clinical trial with biochemical assessment.

BACKGROUND: The innovation of leukocyte platelet-rich fibrin (L-PRF) has added enormous impact on wound healing dynamics especially the field of periodontal regeneration. The release of growth factors (GF) is thought to improve the clinical outcomes in infrabony defects. The aim of this study was to evaluate the clinical effect of covering L-PRF contained infrabony defects with collagen membranes (CM), and to compare their GF release profile to uncovered L-PRF defects and open flap debridement (OFD). METHODS: Thirty non- smoking patients with infrabony pockets participated to be randomly assigned to OFD group (n = 10), L-PRF group (n = 10), or L-PRF protected CM group (n = 10). Plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL) and the radiographic defect base fill (DBF) were measured at baseline and at 6 month following surgical intervention. Gingival crevicular fluid samples were obtained on days 1, 3, 5, 7, 14, 21 and 30 days following surgery for the Platelet Derived Growth Factor-BB (PDGF-BB) and Vascular Endothelial Growth Factors (VEGF) release profile evaluation. RESULTS: For all patients, a statistically significant (P ≤ 0.05) reduction in PI, GI, PD and CAL were reported throughout the study period. Differences between the three treatment modalities were not statistically significant. PRF + CM showed a statistically significant DBF compared to OFD and L-PRF groups at follow up. Quantitative analysis of PDGF-BB and VEGF levels demonstrated a statistically significant (P < 0.001) decline between measurement intervals for all groups with no statistically significant differences between the three groups. CONCLUSION: Within the limitations of this study, L-PRF coverage with CM may augment defect base fill through its mechanical protective effect without enhancement in the release profile of VEGF and PDGF. The non-significant intergroup differences question the validity of the claimed extra physiologic concentration of GF offered by L-PRF harvests. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov (NCT05496608), (11/08/2022).

Salivary Vascular Endothelial Growth Factor and Epidermal Growth Factor Levels in Patients with Recurrent Aphthous Stomatitis: a Meta-Analysis.

Recurrent aphthous stomatitis (RAS) has been identified as a common oral lesion with an unknown pathogenesis. Various studies have been conducted to show the important role of two factors named epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in RAS, but certain results have not been achieved. The present meta-analysis was conducted to evaluate the salivary levels of EGF and VEGF in patients with RAS. For this purpose, the related articles in the Web of Science, PubMed, Embase, ProQuest and Scopus databases until January 2022 were searched and their abstracts were studied. Google scholar and scientific information database were also searched for articles in Persian. The searches were completed by the medical subject heading terms considering "recurrent aphthous stomatitis" and "saliva" in combination with "EGF" or "VEGF" keywords. All case control studies that evaluated the salivary levels of EGF and VEGF in patients with RAS were included in this study. To evaluate statistical heterogeneity between the studies, Cochrane Q and I2 tests were adopted. The extracted data then were used in the analysis process based on comprehensive meta-analysis software. Originally, 619 articles were considered, of which 7 articles were selected. According to this meta-analysis, salivary EGF and VEGF levels were significantly lower in the active and remission period of RAS than in healthy individuals (pValue< 0.05). In addition, salivary levels of these factors were significantly lower in the active stage of RAS than in the healing phase. This review study suggests that decreasing of salivary EGF and VEGF levels have significant role in the development of RAS.

Intravitreal Anti-Vascular Endothelial Growth Factor Therapies for Retinal Disorders.

Vascular endothelial growth factors (VEGFs) are key mediator of retinal and choroidal neovascularization as well as retinal vascular leakage leading to macular edema. As such, VEGF plays an important role in mediating visually significant complications associated with common retinal disorders such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Various drugs that inhibit vascular endothelial growth factors (anti-VEGF therapies) have been developed to minimize vision loss associated with these disorders. These drugs are injected into the vitreous cavity in a clinic setting at regular intervals. This article provides an overview of the various anti-VEGF drugs used in ophthalmology and the common retinal conditions that benefit from this therapy.