Lymphedema of the Head and Neck-Where Do We Stand and Where We Are Headed.

Great advancements have been made in the management of lymphedema of the extremities with lymphatic surgery. However, lymphedema of other regions, including head and neck, has remained neglected. Recent discovery of lymphatic system in the brain and the communication between intracranial and paracranial lymphatic systems has drawn attention to the head and neck lymphatics. Lymphedema of the head and neck region can result from inherent abnormality of the lymphatic system (primary) or be caused by accidental or iatrogenic injury to lymphatics (secondary). The head and neck contain a large network of lymphatic tissue. They may be affected by direct tumor infiltration, surgical resection of tumors and surrounding cancer tissue, and/or radiotherapy. Proper screening and counseling of patients before facial aesthetic procedures may avoid managing the distress of lymphedema postprocedure. Progression of head and neck lymphedema (HNL) can lead to chronic inflammatory, fibrosclerotic, and fibrofatty deposition, resulting in permanent deformity and disability. Patients may experience functional impairment, including skin changes, pain, range of motion limitations, contracture, dysphagia, dysarthria, dyspnea, and trismus, all leading to reduced quality of life. Despite these known disabilities, HNL is underdiagnosed due to a lack of awareness about this entity and of tools available for measuring internal or external swelling. The authors' article comprehensively reviews the current diagnostic methods and management strategies and what lies ahead.

Artificial Intelligence-Based Indocyanine Green Lymphography Pattern Classification for Management of Lymphatic Disease.

Background: Lymphedema diagnosis relies on effective imaging of the lymphatic system. Indocyanine green (ICG) lymphography has become an essential diagnostic tool, but globally accepted protocols and objective analysis methods are lacking. In this study, we aimed to investigate artificial intelligence (AI), specifically convolutional neural networks, to categorize ICG lymphography images patterns into linear, reticular, splash, stardust, and diffuse. Methods: A dataset composed of 68 ICG lymphography images was compiled and labeled according to five recognized pattern types: linear, reticular, splash, stardust, and diffuse. A convolutional neural network model, using MobileNetV2 and TensorFlow, was developed and coded in Python for pattern classification. Results: The AI model achieved 97.78% accuracy and 0.0678 loss in categorizing images into five ICG lymphography patterns, demonstrating high potential for enhancing ICG lymphography interpretation. The high level of accuracy with a low loss achieved by our model demonstrates its effectiveness in pattern recognition with a high degree of precision. Conclusions: This study demonstrates that AI models can accurately classify ICG lymphography patterns. AI can assist in standardizing and automating the interpretation of ICG lymphographic imaging.

Current and Future Implications of Lymphedema Surgery in Head and Neck Reconstruction.

In this study, the authors shed light on the underappreciated realm of head and neck lymphedema (HNL) amid the backdrop of significant advancements in extremity lymphedema management. Despite its prevalence and impact, HNL has long been overlooked, attributed to its subtle symptom presentation and lack of awareness among primary care providers. The study delves into the unique challenges associated with diagnosing and treating HNL, emphasizing the predominance of internal swelling over external manifestations. The authors advocate for the refinement and standardization of outcome measures and the integration of innovative techniques such as indocyanine green lymphography and patient-reported outcomes.

Frontal sinus hypoplasia in unoperated older patients with craniosynostosis: a pilot study.

PURPOSE: The purpose of this study is to determine whether patients with unoperated craniosynostosis have different frontal sinus pneumatization than unaffected controls. METHODS: Retrospective review was performed between 2009 and 2020 of previously unoperated patients with craniosynostosis older than 5 years old at first presentation to our institution. Total frontal sinus volume (FSV) was calculated using 3D volume rendering tool in Sectra IDS7 PACS system. Age-matched normative FSV data was collected from 100 normal CT scans for the control group. The two groups were statistically compared using Fisher's exact test and T-test. RESULTS: Study group included nine patients, 5-39 years old, median age 7 years. Frontal sinus pneumatization was absent in 12% of the normal 7-year-old controls, while frontal sinus pneumatization was absent in 89% of the studied craniosynostosis patients (p < .001). Mean FSV of the study group (113 ± 340 mm3) was significantly different from that of age matched control mean FSV (2016 ± 2529 mm3) (p = .027). CONCLUSIONS: Frontal sinus pneumatization is suppressed in unreleased craniosynostosis and may be an intracranial space conservation phenomenon. This absent frontal sinus can have implications in future frontal region trauma and frontal osteotomies.

Weight gain is an early indicator of injury in ex vivo normothermic limb perfusion (EVNLP).

PURPOSE: There are no established criteria for discontinuing ex vivo normothermic limb perfusion (EVNLP) before irreversible damage occurs. This study evaluates weight gain as an indicator of injury during EVNLP. METHODS: Sixteen Yorkshire pig forelimbs were procured and preserved using EVNLP with a hemoglobin-based oxygen carrier (HBOC-201) or static cold storage. EVNLP continued until termination criteria were met: arterial pressure ≥ 115 mm Hg, compartment pressure > 30 mm Hg, or 20% reduction of oxygen saturation. Limb weight, contractility, hemodynamics, perfusate electrolytes, metabolites and gases were recorded. Muscles were biopsied 6-h, and muscle injury scores (MIS) calculated. Forearm compartment pressures and indocyanine green (ICG) angiography were recorded at endpoint. Outcomes were compared at 2%, 5%, 10%, and 20% limb weight gain. RESULTS: EVNLP lasted 20 ± 3 h. Weight gain was observed after 13 ± 5 h (2%), 15 ± 6 h (5%), 16 ± 6 h (10%), and 19 ± 4 h (20%). Weight correlated positively with MIS (ρ = 0.92, p < 0.0001), potassium (ρ = -1.00, p < 0.0001), pressure (ρ = 0.78, p < 0.0001), and negatively with contractility (ρ = -0.96, p = 0.011). At 5% weight gain, MIS (p < 0.0001), potassium (p = 0.03), and lactate (p < 0.0001) were significantly higher than baseline. Median muscle contractility was 5 [3-5] at 2% weight gain, 4 [1-5] at 5%, 3 [0-4] and 2 [0-2] at 10% and 20%, respectively. At 20% weight gain, contractility was significantly lower than baseline (p = 0.003). Percent weight gain correlated negatively with endpoint ICG hoof fluorescence (r = -0.712, p = 0.047). CONCLUSIONS: Weight gain correlated with microscopic muscle injury and was the earliest evidence of limb dysfunction. Weight gain may serve as a criterion for discontinuation of EVNLP.

Cyclosporine and Pentoxifylline laden tailored niosomes for the effective management of psoriasis: In-vitro optimization, Ex-vivo and animal study.

Psoriasis is a chronic skin inflammatory auto-immune disorder. Cyclosporine is the drug of choice in severe cases of psoriasis for systemic administration. But its systemic administration leads to some serious side effects like nephrotoxicity and cardiovascular disorders. Pentoxifylline is reported to reduce such side effects of cyclosporine and also it is found useful in the management of psoriasis. In this study, Box-Behnken design was used to prepare and optimize Cyclosporine and Pentoxifylline loaded niosomes. The optimized niosomes were prepared using cholesterol and surfactant (7:3), a total of 500 µmol. Ratio of Tween 80 to span 80 for the preparation of optimized niosome was 0.503 (tween80:span80), and hydration and sonication time were kept at 60 min and 10 min, respectively. Size, Poly Dispersity Index, zeta potential, and % entrapment efficiency of Pentoxifylline and cyclosporine, for optimized niosomes were found to be 179 nm, 0.285, -37.5 mV, 84.6%, and 75.3%, respectively. The optimized niosomes were further studied for in-vitro skin permeation and skin deposition. Though niosomes significantly influenced the permeation of both drugs, only a small amount of drug (both cyclosporine and Pentoxifylline) was permeated through the skin. In comparison with the permeation, the quantity of drug retained in the stratum corneum and viable epidermis (SC and VED) was very high. In the in-vivo studies conducted on mice induced with psoriasis using imiquimod, both the histopathology and psoriasis area severity index has shown marked improvement in the skin condition of mice treated with niosomes loaded with Pentoxifylline and cyclosporine, in comparison with the solution/suspension of individual drugs. The study shows that niosomes could be effectively used for the simultaneous delivery of cyclosporine and Pentoxifylline for the better management of psoriasis.

A Recent Update: Solid Lipid Nanoparticles for Effective Drug Delivery.

Solid lipid nanoparticles (SLNs) are one of the developed technologies for addressing the bioavailability and targeting issues of drug delivery. In this review article, we attempted to incorporate all the essential details of SLNs like various methods of preparation, different models of SLNs, updated characterization methods, in vivo behavior (uptake), their applications, route of administration as well as advancements taken place in the field of delivery of biological drugs like gene vector, new adjuvant for vaccines, protein, and peptide with SLNs. Surface modified SLNs hold excellent potential for targeted and controlled drug delivery which is discussed and summarized. Based on the available data, the future success of SLNs is widened because they could be easily fabricated with various functionalities which would display enormous potential for targeting and diagnosing various diseases. This review would help the budding researchers to find out the unexplored areas of SLNs with the present discussion that reframes the potential of SLNs by gathering the various research findings of SLNs in tabular form along with the approved patent technologies of SLNs.

A comprehensive review on possibilities of treating psoriasis using dermal cyclosporine.

Psoriasis is an autoimmune, chronic proliferative, inflammatory skin disease with high comorbidity. Psoriasis is not a curable disease; it can only be managed. Cyclosporine A (CyA) is one of the FDA-approved immunosuppressant drug used in severe Psoriasis. Till date only oral route is used for its administration. Administration of CyA by this route causes serious side effects such as hypertension and renal toxicity. Due to these side effects, a number of researches have been done and taking place in the current times for the dermal delivery of CyA for the management of psoriasis. Dermal delivery of CyA is not an easy task because of its physiochemical properties like high molecular weight, lipophilicity and resistance offered by stratum corneum (SC). Because of the above problems in the dermal delivery a number of new approaches such as nanolipid carriers, microemulsion, liposomes, niosomes etc. are explored. To those deep findings for psoriasis management with dermal delivery of CyA have not been discussed. This comprehensive review includes all the studies, advancements and their critical findings which took place in the recent times for the dermal delivery of CyA and along with the suitable modification needed for the efficient dermal delivery of CyA are also suggested.

A Review on Recent Trends in Green Synthesis of Gold Nanoparticles for Tuberculosis.

Tuberculosis (TB) is a contagious disease that has affected mankind. The anti-TB treatment has been used from ancient times to control symptoms of this disease but these medications produced some serious side effects. Herbal products have been successfully used for the treatment of TB. Gold is the most biocompatible metal among all available for biomedical purposes so Gold nanoparticles (GNPs) have sought attention as an attractive biosynthesized drug to be studied in recent years for bioscience research. GNPs are used as better catalysts and due to unique small size, physical resemblance to physiological molecules, biocompatibility and non-cytotoxicity extensively used for various applications including drug and gene delivery. Greenly synthesized GNPs have much more potential in different fields because phytoconstituents used in GNP synthesis itself act as reducing and capping agents and produced more stabilized GNPs. This review is devoted to a discussion on GNPs synthesis with herbs for TB. The main focus is on the role of the natural plant bio-molecules involved in the bioreduction of metal salts during the GNPs synthesis with phytoconstituents used as antitubercular agents.

Mannosylated Solid Lipid Nanocarriers of Chrysin to Target Gastric Cancer: Optimization and Cell Line Study.

BACKGROUND: Despite significant biological effects, the clinical use of chrysin has been restricted because of its poor oral bioavailability. OBJECTIVE: The purpose of the present research was to investigate the targeting potential of Mannose decorated chrysin (5,7- dihydroxyflavone) loaded solid lipid nanocarrier (MC-SLNs) for gastric cancer. METHODS: The Chrysin loaded SLNs (C-SLNs) were developed, optimized, characterized and further mannosylated. The C-SLNs were developed with a high shear homogenizer, optimized with 32 full factorial designs and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD) and Scanning Electron Microscope (SEM) and evaluated for particle size/polydispersity index, zeta-potential, entrapment efficiency, % release and haemolytic toxicity. The ex-vivo cytotoxicity study was performed on gastric cancer (ACG) and normal cell lines. RESULTS: DSC and XRD data predict the chrysin encapsulation in the lipid core and FTIR results confirm the mannosylation of C-SLNs. The optimized C-SLNs exhibited a narrow size distribution with a particle size of 285.65 nm. The % Entrapment Efficiency (%EE) and % controlled release were found to be 74.43% and 64.83%. Once C-SLNs were coated with mannose, profound change was observed in a dependent variable - an increase in the particle size of MC-SLNs (307.1 nm) was observed with 62.87% release and 70.8% entrapment efficiency. Further, the in vitro studies depicted MC- SLNs to be least hemolytic than pure chrysin and C-SLNs. MC-SLNs were most cytotoxic and were preferably taken up ACG tumor cells as evaluated against C-SLNs. CONCLUSION: These data suggested that the MC-SLNs demonstrated better biocompatibility and targeting efficiency to treat gastric cancer.

Cyclosporine laden tailored microemulsion-gel depot for effective treatment of psoriasis: In vitro and in vivo studies.

Psoriasis is a widespread chronic disease affecting 1-3 % of total population. In major cases (>80 %), it is treated by topical application of corticosteroids. However, the topical route is very challenging due to physico-chemical nature of diseased stratum corneum and so no single treatment works for every patient. The oral route showed severe side effects due to systemic immunosuppression, which can be avoided by topical route. The aim of the research work was to investigate cyclosporine loaded microemulsion based gel for effective cyclosporine permeation and retention in the skin tissue for psoriasis treatment. The pseudo ternary phase diagram at three Smix ratios (2:1, 1:1, and 1:2; Tween 80: isopropyl alcohol) were constructed using isopropyl myristate as oil phase. The Smix at 2:1 ratio showed large microemulsion area. The transmission electron microscope images showed spherical non-aggregated oil globules with the size < 50 nm. The selected microemulsion (Cy-2-ME12O55SM) was incorporated in Carbopol 940 gel for topical application. The ex vivo diffusion study showed improved permeation (>24 h) with microemulsion-gel in comparison to cyclosporine suspension. The microemulsion-gel was non-irritating on the rabbit skin. In drug retention studies, microemulsion-gel showed high drug retention (trapping, 38.92 %) in the skin tissue, which was due to destabilization of microemulsion after penetration in the skin layer causing precipitation of cyclosporine. The depot effect due to cyclosporine precipitates could be helpful for sustained effect of cyclosporine for the effective treatment of psoriasis.

Solubilization of Carbamazepine in TPGS Micelles: Effect of Temperature and Electrolyte Addition.

D-α-Tocopheryl polyethylene glycol succinate (TPGS), a polyethylene glycol condensate, is a biologically important nonionic amphiphile. In this study, we report on aqueous solution behavior of TPGS with a focus on its clouding, surface activity, micellar characteristics, and solubilization capacity for a model hydrophobic drug, carbamazepine (CBZ). Micelles were characterized by dynamic light and small-angle neutron scattering studies as a function of temperature, salt addition, and CBZ solubilization. TPGS showed a cloud point of 78°C and possessed good surface activity (as observed from surface tension reduction and adsorption parameters). The critical micelle concentration (CMC), obtained from surface tension and fluorescence studies, was 0.02 mM. Scattering studies showed formation of stable micelles (average diameter-12 nm), exhibiting no significant changes in size upon salt addition (up to 1 M NaCl), CBZ incorporation (up to 5 mM), and temperature increase (40°C). Micelles in 5 wt% TPGS showed about twentyfold enhancement in CBZ solubility. Considering the remarkable CBZ solubilization and its positioning in the core, we suggest that the formulation can be exploited as a sustained delivery vehicle.

Novel Solid Lipid Nanocarrier of Glibenclamide: A Factorial Design Approach with Response Surface Methodology.

BACKGROUND: In the present investigation, a factorial design approach attempt was applied to develop the Solid Lipid Nanoparticles (SLN) of Glibenclamide (GLB) a poorly water-soluble drug (BCS -II) used in the treatment of type 2 diabetes. OBJECTIVES: Prime objectives of this experiment are to optimize the SLN formulation of Glibenclamide and improve the therapeutic effectiveness of the developed formulation. METHODS: Glibenclamide loaded SLNs (GLB-SLN) were fabricated by High speed homogenization technique. A 32-factorial design approach has been employed to assess the influence of two independent variables, namely amount of Poloxamer 188 and Glyceryl Monostearate on entrapment efficiency (% EE) (Y1), Particle Size (nm) (Y2), % drug release at 8hr Q8 (Y3) and 24 hr Q24 (Y4) of prepared SLNs. Differential scanning calorimetry analysis revealed the compatibility of the drug into lipid matrix with a surfactant, while Transmission electron and Scanning electron microscopy studies indicated the size and shape of SLN. RESULTS: The entrapment efficiency, particle size, Q8 and Q24 of the optimized SLNs were 88.93%, 125 nm, 31.12±0.951% and 86.07±1.291% respectively. Optimized GLB-SLN formula was derived from an overlay plot. Three-dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. In vivo testing of the GLB-SLN in diabetic albino rats demonstrated the significant antidiabetic effect of GLB-SLN. CONCLUSION: The hypoglycemic effect obtained by GLB-SLN remained significantly higher than that given by drug alone and marketed formulation, further confirming the higher therapeutic effectiveness of the GLB-SLN formulation. Our findings suggested the feasibility of the investigated system for oral administration of Glibenclamide.

Multiple response optimisation of processing and formulation parameters of pH sensitive sustained release pellets of capecitabine for targeting colon.

PURPOSE: To optimise the Eudragit/Surelease®-coated pH-sensitive pellets for controlled and target drug delivery to the colon tissue and to avoid frequent high dosing and associated side effects which restrict its use in the colorectal-cancer therapy. METHODS: The pellets were prepared using extrusion-spheronisation technique. Box-Behnken and 32 full factorial designs were applied to optimise the process parameters [extruder sieve size, spheroniser-speed, and spheroniser-time] and the coating levels [%w/v of Eudragit S100/Eudragit-L100 and Surelease®], respectively, to achieve the smooth optimised size pellets with sustained drug delivery without prior drug release in upper gastrointestinal tract (GIT). RESULTS: The design proposed the optimised batch by selecting independent variables at; extruder sieve size (X1 = 1 mm), spheroniser speed (X2 = 900 revolutions per minute, rpm), and spheroniser time (X3 = 15 min) to achieve pellet size of 0.96 mm, aspect ratio of 0.98, and roundness 97.42%. The 16%w/v coating strength of Surelease® and 13%w/v coating strength of Eudragit showed pH-dependent sustained release up to 22.35 h (t99%). The organ distribution study showed the absence of the drug in the upper part of GIT tissue and the presence of high level of capecitabine in the caecum and colon tissue. Thus, the presence of Eudragit coat prevent the release of drug in stomach and the inner Surelease® coat showed sustained drug release in the colon tissue. CONCLUSION: The study demonstrates the potential of optimised Eudragit/Surelease®-coated capecitabine-pellets for effective colon-targeted delivery system to avoid frequent high dosing and associated systemic side effects of drug.