Update on the Molecular Pathology of Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, originating from keratinocytes of the spinous layer. Numerous risk factors have been discovered for the initiation and growth of this type of cancer, such as exposure to UV and ionizing radiation, chemical carcinogens, the presence of immunosuppression states, chronic inflammation, infections with high-risk viral strains, and, last but not least, the presence of diseases associated with genetic alterations. The important socio-economic impact, as well as the difficulty associated with therapy for advanced forms, has made the molecular mechanisms underlying this neoplasia more and more intensively studied, with the intention of achieving a better understanding and advancing the treatment of this pathology. This review aims to provide a brief foray into the molecular, genetic, and epigenetic aspects of this cancer, as well as the treatment methods, ranging from the first used to the latest targeted therapies.

The microbial condition of Scottish wild deer carcasses collected for human consumption and the hygiene risk factors associated with Escherichia coli and total coliforms contamination.

Wild deer hunting is necessary in Scotland to control deer population density, with most carcasses being processed for human consumption. As limited information is available on the microbial condition of Scottish venison, we studied the variation of total coliforms and Escherichia coli (E. coli) on 214 wild deer carcasses collected from six approved establishments. Samples were collected from the hide, body cavity and external surface of each carcass and mean values were determined following bacterial plate counts. The mean log10/cm2 coliforms were 5.78 (hide), 6.80 (body cavity) and 6.36 (external surface). The mean log10/cm2E. coli were 1.82 (hide), 2.27 (body cavity) and 2.17 (external carcass). Significantly higher coliforms counts were associated with storage-to-dressing times above 6 days and with longer transport distances. Risk factors that increased E. coli were red deer species, ambient temperature above 7 °C during hunting, dirty hides, faecal contamination and moisture or slimy film on the carcass. Although the bacterial counts obtained in this study indicated some hygienic processing, for around half of the carcasses, the E. coli counts were above 2 log10/cm2. Therefore, the above risk factors suggest a few handling hygiene practices that should be further improved to enhance quality and safety.

Evaluation of a Harmonized Undergraduate Catalog for Veterinary Public Health and Food Hygiene Pedagogy in Europe.

Current and emerging veterinary public health (VPH) challenges raised by globalization, climate change, and industrialization of food production require the veterinarian's role to evolve in parallel and veterinary education to adapt to reflect these changes. The European Food Hygiene catalog was developed to provide a list of topics relevant to Day One Competencies in VPH. A study was undertaken to ensure that the catalog and teaching practices were pertinent to the work of public health veterinarians. Relevant stakeholders were consulted using questionnaires and semi-structured interviews. A long questionnaire was distributed to 49 academics teaching VPH in European veterinary schools to review topics listed in the catalog. Eighteen responses were received (36.7%), representing 12 European countries. There was general agreement that most topics were appropriate for the undergraduate VPH curriculum. A short questionnaire was distributed to 348 European veterinarians working in the industry. Twenty-four questionnaires (6.7%) were received, representing eight European countries. Despite the low participation rate, topics needing greater emphasis in the undergraduate curriculum included Hazard Analysis Critical Control Points (HACCP), food microbiology, and audits. Seven semi-structured interviews with public health veterinarians working in the UK identified the need for curricular changes including greater practical experience and a shift from a focus on meat inspection to risk management. This may be partly achieved by replacing traditional lectures with authentic case-based scenarios. The study findings can be used to inform the future direction to VPH education for veterinary students across Europe.

The Effect of Intravitreal Ocriplasmin on Hue Discrimination.

SIGNIFICANCE: We report 13 patients who received ocriplasmin for symptomatic vitreomacular adhesion. Farnsworth-Munsell 100 (FM 100) hue test total error score (TES) increased from baseline to month 1, before recovering at year 1. Ocriplasmin may alter hue discrimination. PURPOSE: This study aimed to determine whether intravitreal ocriplasmin affects hue discrimination. METHODS: Thirteen patients with symptomatic vitreomacular adhesion received intravitreal ocriplasmin 125 µg. Patients underwent full ocular examination, optical coherence tomography, and FM 100 hue test at baseline, 1 week, 1 month, and 1 year. RESULTS: Mean age was 74.8 years. The median baseline FM 100 TES was similar in the injected and fellow eyes (272 vs. 252, respectively). Median TES in the injected eye increased from 272 to 348 at 1 week (median difference compared with baseline, +52.0; 98.8% confidence interval of difference, -64.0 to 184.0; P = .29), decreased to 324 at 1 month (median difference compared with baseline, -4.0; 98.8% confidence interval of difference, -44.0 to 256.0; P = .40), and decreased to 268 at 1 year (median difference compared with baseline, -108.0; 93.8% confidence interval of difference, -200.0 to 52.0; P = .19). Two patients (15.4%) had anatomic release of vitreomacular adhesion, occurring within 1 month of injection. CONCLUSIONS: Ocriplasmin may alter hue discrimination, but larger studies are required to provide sufficient power to detect or exclude a statistically significant effect. Longer follow-up is needed to determine the duration of any effect.

Digitally Enhanced Methods for the Diagnosis and Monitoring of Treatment Responses in Actinic Keratoses: A New Avenue in Personalized Skin Care.

Non-melanocytic skin cancers represent an important public health problem due to the increasing incidence and the important local destructive potential. Thus, the early diagnosis and treatment of precancerous lesions (actinic keratoses) is a priority for the dermatologist. In recent years, non-invasive skin imaging methods have seen an important development, moving from simple observational methods used in clinical research, to true diagnostic and treatment methods that make the dermatologist's life easier. Given the frequency of these precancerous lesions, their location on photo-exposed areas, as well as the long treatment periods, with variable, imprecise end-points, the need to use non-invasive imaging devices is increasingly evident to complete the clinical observations in the diagnosis and treatment of these lesions, with the aim of increasing accuracy and decreasing the adverse effects due to long treatment duration. This is the first review that brings together all skin imaging methods (dermoscopy, reflectance confocal microscopy, ultrasonography, dermoscopy-guided high frequency ultrasonography, and optical coherence tomography) used in the evaluation of actinic keratoses and their response to different treatment regimens.

Platelet-Rich Plasma in Dermatology: New Insights on the Cellular Mechanism of Skin Repair and Regeneration.

The skin's recognised functions may undergo physiological alterations due to ageing, manifesting as varying degrees of facial wrinkles, diminished tautness, density, and volume. Additionally, these functions can be disrupted (patho)physiologically through various physical and chemical injuries, including surgical trauma, accidents, or chronic conditions like ulcers associated with diabetes mellitus, venous insufficiency, or obesity. Advancements in therapeutic interventions that boost the skin's innate regenerative abilities could significantly enhance patient care protocols. The application of Platelet-Rich Plasma (PRP) is widely recognized for its aesthetic and functional benefits to the skin. Yet, the endorsement of PRP's advantages often borders on the dogmatic, with its efficacy commonly ascribed solely to the activation of fibroblasts by the factors contained within platelet granules. PRP therapy is a cornerstone of regenerative medicine which involves the autologous delivery of conditioned plasma enriched by platelets. This is achieved by centrifugation, removing erythrocytes while retaining platelets and their granules. Despite its widespread use, the precise sequences of cellular activation, the specific cellular players, and the molecular machinery that drive PRP-facilitated healing are still enigmatic. There is still a paucity of definitive and robust studies elucidating these mechanisms. In recent years, telocytes (TCs)-a unique dermal cell population-have shown promising potential for tissue regeneration in various organs, including the dermis. TCs' participation in neo-angiogenesis, akin to that attributed to PRP, and their role in tissue remodelling and repair processes within the interstitia of several organs (including the dermis), offer intriguing insights. Their potential to contribute to, or possibly orchestrate, the skin regeneration process following PRP treatment has elicited considerable interest. Therefore, pursuing a comprehensive understanding of the cellular and molecular mechanisms at work, particularly those involving TCs, their temporal involvement in structural recovery following injury, and the interconnected biological events in skin wound healing and regeneration represents a compelling field of study.

Vasculitis-Like Hemorrhagic Herpes Zoster and HIV Infections: An Intricate Association.

Herein, we report the case of a 69-year-old patient who presented to our dermatology clinic for a skin eruption characterized by grouped hemorrhagic vesicles and erosions covered by hemorrhagic crusts on an erythematous background located on the lower right limb. The lesions were small, clustered, and variable in size (diameters between one and 10 mm) and located at the level of the L4-L5 dermatomes. The rash had started three to five days after the complete COVID-19 vaccination scheme with the BNT162b2 Pfizer BioNTech vaccine and had been accompanied by a flu-like syndrome. The histopathological examination established the diagnosis of leukocytoclastic vasculitis potentially in the context of a cytopathic zoster phenomenon. The atypical aspect of the zosterian eruption required additional laboratory work-up to identify possible causes of immunosuppression, i.e., screening for the presence of the human immunodeficiency virus (HIV) infection, solid cancers, as well as measurement of serum immunoglobulin concentrations, which revealed that the subject was HIV-positive. Antiviral treatment was started, with a favorable evolution of the lesions, and the patient was referred to an infectious diseases clinic for initiation of antiretroviral therapy (ART).

Subepidermal Low-Echogenic Band-Its Utility in Clinical Practice: A Systematic Review.

High-frequency ultrasonography (HF-USG) is a relatively new imaging method that allows the evaluation in a non-invasive manner of the skin layers and skin appendages. It is a diagnostic tool with increasing usefulness in numerous dermatological pathologies. High reproducibility, non-invasiveness and short diagnostic time make this method an increasingly used tool in dermatological practice. The subepidermal low-echogenic band is a relatively newly described parameter that seems to be a marker not only of intrinsic and extrinsic skin aging, but also of inflammatory processes taking place at the skin level. This systematic review aims to evaluate the role that SLEB has in the diagnosis and monitoring of the treatment of some inflammatory and non-inflammatory dermatological conditions, as well as its utility as a disease marker.

Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial.

BACKGROUND/AIM: To assess the long-term safety and efficacy of epimacular brachytherapy (EMB) for chronic, active, neovascular age-related macular degeneration (nAMD). METHODS: This pivotal, randomised, controlled surgical device trial recruited patients with chronic nAMD receiving intravitreal ranibizumab from 24 UK hospitals. Participants were randomised to either pars plana vitrectomy with 24 Gray EMB and pro re nata (PRN) ranibizumab (n=224) or PRN ranibizumab monotherapy (n=119). Although masking was not possible, masked clinicians assessed best-corrected visual acuity (BCVA) and imaging. After month 24, participants reverted to standard care, with either ranibizumab or aflibercept, returning for a month 36 study visit. RESULTS: Of 363 participants, 309 (85.1%) completed month 36. The number of injections was 12.1±8.1 in the EMB group versus 11.4±6.1 in the ranibizumab group (difference 0.7, 95% CI of difference -0.9 to 2.3, p=0.41) between months 1 and 36, and 3.6±3.3 (n=200) versus 3.9±2.7 (n=102) (difference -0.3, 95% CI of difference -1.0 to 0.4, p=0.43) between months 25 and 36 (standard care). Over 36 months, BCVA change was -19.7±18.5 letters in the EMB group and -4.8±12.5 in the ranibizumab group (difference -14.9, 95% CI of difference -18.5 to -11.2, p<0.0001). The month 36 BCVA of 20 EMB-treated participants with microvascular abnormalities (MVAs) at month 24 was similar to EMB-treated participants without MVAs (-21.8 vs -19.4 letters, p=0.65). CONCLUSION: EMB does not reduce the number of anti-vascular endothelial growth factor (VEGF) injections, either within or outside of a trial setting, and is associated with worse BCVA than anti-VEGF monotherapy. TRIAL REGISTRATION NUMBER: NCT01006538.

Bilateral Giant Fornix Syndrome Associated with Serratia Marcescens.

An 82-year-old woman with macular degeneration receiving intravitreal bevacizumab, presented with 5-months history of muco-purulent blepharo-kerato-conjunctivitis, resistant to multiple topical antibiotics. Visual acuities were 20/25 right and 20/30 left. She had patent nasolacrimal systems, bilateral blepharoptosis, deep superior fornices (21mm right, 22mm left) with muco-purulent discharge, upper tarsal papillae, and punctate keratitis. Bilateral giant fornix syndrome (GFS) was diagnosed, and forniceal swabs grew Serratia marcescens and Pseudomonas aeruginosa, despite current use of intensive topical moxifloxacin. Topical preservative-free Povidone-Iodine 5% twice-daily, two-hourly weaning course of Prednisolone acetate 1% and Ciprofloxacin 250 mg twice-daily were added with complete resolution within 1 week and no recurrence after 3 months. Serratia conjunctivitis has not been previously reported in association with GFS. Conjunctival flora alteration following previous peri-procedural antibiotics and antiseptics, in the setting of a large fornix with redundant, inflamed conjunctiva, may explain the colonization with this opportunistic organism. Topical povidone-iodine 5% appears to be effective for multi-drug resistant opportunistic Serratia conjunctivitis in association with GFS.

Cataract surgery outcomes in eyes with previous radial keratotomy.

BACKGROUND/OBJECTIVES: This study shows the visual and refractive outcomes of cataract surgery in patients with previous radial keratotomy (RK). SUBJECTS/METHODS: This is a retrospective case series of 100 eyes (65 patients) with previous RK who had undergone routine cataract surgery with a monofocal intraocular lens implant (IOL) at Moorfields Eye Hospital, London, United Kingdom, between January 2004 and December 2018. RESULTS: Mean age at the time of surgery was 59.8 years; 39% eyes had ocular copathology. Best-corrected visual acuity (LogMAR; median, interquartile range) improved from 0.30 (0.22, 0.55) to 0.06 (-0.02, 0.21) in eyes without copathology, and from 0.56 (0.30, 1.00) to 0.20 (0.00, 0.20) in eyes with copathology. Haigis formula (19 eyes) resulted in a median prediction error of -0.31 D (-1.07, +0.05), versus -0.55 D (-1.23, +0.22) for Double-K SRK/T (55 eyes) and +0.93 D (0.20, 2.31) for SRK/T (18 eyes). At the final follow-up, 52.6% eyes were within 0.5 D and 68.4% within 1 D of the predicted spherical equivalent for Haigis, versus 32.7% and 52.7% for Double-K SRK/T, and 27.8% and 38.9% for SRK/T. The most frequent complication was RK incision dehiscence (8%). CONCLUSIONS: Although the best-corrected visual acuity outcomes compare with the UK national benchmarks, significantly fewer eyes with previous RK achieved the level of unaided distance visual acuity to allow spectacle independence. Surgeons should be aware of the increased likelihood of wound dehiscence and plan surgery accordingly. Haigis formula tended to have a better predictability of the postoperative spherical equivalent and, since introduced, was the preferred choice for IOL calculation in this group of patients.

A word-of-mouth perspective on consumers of family medicine services: a case study.

In an increasingly competitive health care market, family physicians have to elaborate and implement new strategies to attract potential patients. A useful and powerful method is word-of-mouth (WOM) because it shapes the consumers' attitudes and behaviours. Based on the recommendations of actual consumers, potential health care patients choose their family physicians. The aim of this study was to investigate the usefulness of WOM in family medicine and determine the key factors in recommending a certain family physician. The sample consisted of 338 patients under the supervision of a family physician, and the instrument for collecting data was a self-administered questionnaire. The findings revealed that the most important factors in spreading WOM are the communication skills and the expertise of the family physician. In addition, for patients between 27-33 years and 41-47 years, expertise is an absolute skill, whereas, for the health care consumers between 21 and 26 years, communication skills are essential in spreading WOM. Further, WOM becomes relevant in the family physician's activity as it may contribute to the delivery of value and in building sustainable physician-patient relationships.

Healthcare Disparities in the Management of Indolent Mycosis Fungoides.

Mycosis fungoides represents the most common cutaneous T-cell lymphoma, clinically manifested with evolving skin lesions, including patches, plaques, tumors, and erythroderma. Early diagnosis remains difficult to establish because it mimics several benign skin conditions, but maintaining a high index of suspicion for the disease is essential in preventing the progression of a potentially fatal disease. We report the case of a 69-year-old female who presented in our dermatology clinic in 2018 with scaly, indurated, itchy erythematous-violaceus patches and plaques, and tumors disseminated throughout the skin evolving for nine years. Skin biopsy supplemented with immunohistochemical staining established the diagnosis of mycosis fungoides. Due to the equivocal clinical presentation and the lack of extracutaneous manifestations, the patient received conventional therapy according to the stage of the disease. The rapidly progressive evolution of the cutaneous lesions in the last year of the disease determined the patient's death despite instituting systemic chemotherapy. Patient follow-up and a multidisciplinary approach are essential to diagnose and manage this disease in its early stages. This will prevent the progression to a life-threatening malignancy and the use of immunosuppressive therapy, which can cause serious side effects.

Confidence of UK Ophthalmology Registrars in Managing Posterior Capsular Rupture: Results from a National Trainee Survey.

INTRODUCTION: To establish the level of confidence amongst UK ophthalmology specialist registrars (residents) in managing posterior capsule rupture (PCR) during cataract surgery. METHODS: An online nine-item questionnaire was distributed to all registrars, recruited nationwide via regional representatives. Data collected included stage of training, number of completed cataract operations, cumulative PCR rate, number of PCRs independently managed, understanding of vitrectomy settings and fluidic parameters and access to simulation. Respondents self-evaluated their confidence in managing PCR with vitreous loss. RESULTS: Complete responses were obtained from 248 registrars (35% response rate). Mean number of phacoemulsification procedures performed was 386. For senior registrars (OST 6-7), 35 out of 70 (50%) felt confident to manage PCR independently and 55 out of 70 (78.6%) were either quite confident or very confident at deciding when to implant an intraocular lens during PCR management. Lower confidence levels were noted for junior trainees (OST 1-2). Over 65% of survey respondents had access to relevant simulation. CONCLUSIONS: Our results represent the largest UK survey analysing the confidence of PCR management amongst registrars. Confidence improves with duration of training and increased exposure to management of PCR. However, 50% of senior registrars still lacked confidence to independently manage PCR and vitreous loss. A specific competency-based framework, potentially using a simulator or simulating a PCR event, incorporated into the curriculum may be desirable.

Maximising Societal Benefit From the Control of Neglected Zoonoses: Identifying Synergies and Trade-Offs in the Control of Taenia solium.

Interventions to control or eradicate neglected zoonoses are generally paid for through the public purse and when these interventions focus on the animal hosts, they are often expected to be performed and financed through the state veterinary service. The benefits of control, however, accrue across the human, animal, and environmental spaces and enhance both public and private interests. Additionally, disease control interventions do not take place in a vacuum and the indirect impacts of our actions should also be considered if the societal benefit of interventions is to be maximised. With the caveat that unintended consequences can and will occur, pre-identifying potential synergies and trade-offs in our disease control initiatives allows for them to be considered in intervention design and monitored during programme roll-out. In this paper, using a One Health approach with the example of Taenia solium control, we identify potential indirect impacts which may arise and how these may influence both our choice of intervention and opportunities to optimise the animal, environmental, and societal benefits of control through maximising synergies and minimising trade-offs.