Search

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by liver insufficiency and/or portosystemic shunting. HE is mostly episodic and as such reversible. Hyperammonemia clearly plays a key role in the pathophysiology, but the precise detrimental events in the brain leading to HE remain equivocal. Several pathogenic models have been proposed, but few have been linked to clinical studies and observations. Decreased oxygen metabolism is observed in both type A and C HE and in this review, we advocate that this reflects an actual reduced oxygen demand and not a primary cause of HE. As driving force, we propose that the hyperammonemia via astrocytic glutamine synthetase causes an increased γ-aminobutyric acid (GABA) mediated neuro-inhibition which subsequently leads to an overall decreased energy demand of the brain, something that can be enhanced by concomitant neuroinflammation. This also explains the reversibility of the condition. [ABSTRACT FROM AUTHOR]

Xerosis is highly prevalent in the population aged over 50 years and substantially impacts quality of life due to the associated stigma, related pruritus, and potential sequelae. We propose that the term mature xerosis be used for subjects over 50 who suffer from age‐related xerosis and replace senile xerosis to describe the phenomenon. The etiology of xerosis depends on genetic and environmental factors that affect stratum corneum hydration and skin barrier function. Skincare to restore barrier function is essential in xerosis treatment and is relevant for maintaining and preventing its progression. Many moisturizers and cleansers are available for xerosis; however, they are underutilized by patients with mature xerosis. A panel of eight global dermatologists reviewed the unique aspects of xerosis in mature skin and discussed the specific needs, relevance, and considerations for skincare selection to prevent, treat, and maintain skin with mature xerosis. The panel selected five statements based on evidence from a literature review and the panel's clinical experience to provide clinical considerations and recommendations for dermatologists and other healthcare providers treating patients with mature xerosis. Increased recognition of the burden of xerosis in mature skin is warranted. Gentle cleansers and barrier‐restoring ceramide‐containing moisturizers are essential to xerosis management, reducing signs and symptoms of xerosis, including associated pruritus. [ABSTRACT FROM AUTHOR]

Vaccination before solid organ transplantation is recommended since post-transplantation immunosuppression is known to impair vaccine responses. However, little is known about post-transplantation seroprotection rates in organ transplant recipients vaccinated pre-transplantation. We aimed to investigate the proportion of transplant recipients vaccinated against hepatitis B virus (HBV) and invasive pneumococcal disease (IPD) pre-transplantation at the time of listing for transplantation with post-transplantation seroprotection. We included 136 solid organ transplant (SOT) recipients vaccinated at the time of listing for transplantation. We investigated post-transplantation antibody concentrations against HBV and IPD. Established antibody thresholds were used to define seroprotection. The proportions of SOT recipients with post-transplantation seroprotection were 27.9% (n = 38) and 42.6% (n = 58) against HBV and IPD, respectively. Compared to completing HBV vaccination pre-transplantation, completing post-transplantation vaccination (adjusted odds ratio (aOR): 7.8, 95% CI: 2.5–24.5, p < 0.001) and incomplete vaccination (aOR: 6.3, 95% CI: 1.2–32.6, p = 0.028) were associated with non-response against HBV, after adjustment for confounders. Importantly, patients with seroprotection at the time of listing had lower odds of non-response against HBV (aOR: 0.04, 95% CI: 0.0–0.1, p < 0.001) and IPD (aOR: 0.3, 95% CI: 0.1–0.7, p = 0.007) compared to those without seroprotection. SOT recipients vaccinated pre-transplantation had low post-transplantation seroprotection rates against HBV and IPD. However, SOT recipients with seroprotection at the time of listing had lower odds of non-response, suggesting early vaccination should be a priority. [ABSTRACT FROM AUTHOR]

Background: The development of artificial intelligence (AI) is rapidly expanding, showing promise in the dermatological field. Skin checks are a resource‐heavy challenge that could potentially benefit from AI‐tool assistance, particularly if provided in widely available AI solutions. A novel smartphone application(app)‐based AI system, "SCAI," was developed and trained to recognize spots in paired images of skin, pursuing identification of new skin lesions. This pilot study aimed to investigate the feasibility of the SCAI‐app to identify simulated skin changes in vivo. Materials and methods: The study was conducted in a controlled setting with healthy volunteers and standardized, simulated skin changes (test spots), consisting of customized 3‐mm adhesive spots in three colors (black, brown, and red). Each volunteer had a total of eight test spots adhered to four areas on back and legs. The SCAI‐app collected smartphone‐ and template‐guided standardized images before and after test spot application, using its backend AI algorithms to identify changes between the paired images. Results: Twenty‐four volunteers were included, amounting to a total of 192 test spots. Overall, the detection algorithms identified test spots with a sensitivity of 92.0% (CI: 88.1–95.9) and a specificity of 95.5% (CI: 95.0–96.0). The SCAI‐app's positive predictive value was 38.0% (CI: 31.0–44.9), while the negative predictive value was 99.7% (CI: 99.0–100). Conclusion: This pilot study showed that SCAI‐app could detect simulated skin changes in a controlled in vivo setting. The app's feasibility in a clinical setting with real‐life skin lesions remains to be investigated, where the challenge with false positives in particular needs to be addressed. [ABSTRACT FROM AUTHOR]

Actinic keratosis (AK) classification relies on clinical characteristics limited to the skin's surface. Incorporating sub‐surface evaluation may improve the link between clinical classification and the underlying pathology. We aimed to apply dynamic optical coherence tomography (D‐OCT) to characterize microvessels in AK I‐III and photodamaged (PD) skin, thereby exploring its utility in enhancing clinical and dermatoscopic AK evaluation. This explorative study assessed AK I‐III and PD on face or scalp. AK were graded according to the Olsen scheme before assessment with dermatoscopy and D‐OCT. On D‐OCT, vessel shapes, −pattern and ‐direction were qualitatively evaluated at predefined depths, while density and diameter were quantified. D‐OCT's ability to differentiate between AK grades was compared with dermatoscopy. Forty‐seven patients with AK I‐III (n = 207) and PD (n = 87) were included. Qualitative D‐OCT evaluation revealed vascular differences between AK grades and PD, particularly at a depth of 300 μm. The arrangement of vessel shapes around follicles differentiated AK II from PD (OR = 4.75, p < 0.001). Vessel patterns varied among AK grades and PD, showing structured patterns in AK I and PD, non‐specific in AK II (OR = 2.16,p = 0.03) and mottled in AK III (OR = 29.94, p < 0.001). Vessel direction changed in AK II‐III, with central vessel accentuation and radiating vessels appearing most frequently in AK III. Quantified vessel density was higher in AK I‐II than PD (p ≤ 0.025), whereas diameter remained constant. D‐OCT combined with dermatoscopy enabled precise differentiation of AK III versus AK I (AUC = 0.908) and II (AUC = 0.833). The qualitative and quantitative evaluation of vessels on D‐OCT consistently showed increased vascularization and vessel disorganization in AK lesions of higher grades. [ABSTRACT FROM AUTHOR]

Introduction: Ultraviolet radiation (UVR) is the primary risk factor for keratinocyte carcinomas. Oral supplementation with nicotinamide (NAM) is reported to reduce the formation of new keratinocyte carcinomas. NAM's photoprotection is mediated by enhanced DNA repair. We wanted to explore whether NAM in combination with antiproliferative (metformin [Met]) or antioxidant (phloroglucinol [PG]) compounds could potentially enhance its photoprotective effects. Methods: Hairless mice (C3.Cg-Hrhr/TifBomTac) were treated orally with either a standard dose of NAM monotherapy (NAM-mono; 600 mg/kg) or NAM (400 mg/kg) combined with Met (200 mg/kg) (NAM-Met) or PG (75 mg/kg) (NAM-PG). Mice were irradiated with 3.5 standard erythema doses of UVR three times per week to induce tumour development. Photoprotective effects were based on (i) tumour onset of the first three tumours, (ii) skin photodamage, and (iii) DNA damage (cyclobutane pyrimidine dimers [CPDs] and pyrimidine-pyrimidone (6–4) photoproducts [6-4PPs]). Results: All mice treated with NAM demonstrated a delay in tumour onset and reduced tumour burden compared to the UV control group (NAM, NAM-Met, NAM-PG vs. UV control: p ≤ 0.015). NAM-mono and NAM-PG increased time until all three tumours with no difference between them, indicating a similar degree of photoprotection. NAM-mono had no effect on DNA damage compared to the UV control group (p > 0.05), whereas NAM-PG reduced 6-4PP lesions (p < 0.01) but not CPDs (p > 0.05) compared to NAM-mono. NAM-Met delayed the onset of the third tumour compared to the UV control but demonstrated a quicker onset compared to NAM-mono, suggesting inferior photoprotection compared to nicotinamide monotherapy. Conclusion: NAM-PG was as effective in delaying UVR-induced tumour onset as NAM-mono. The reduction in 6-4PP lesions may indicate that the mechanism of NAM-PG is better suited for photoprotection than NAM-mono. NAM-mono was superior to NAM-Met, indicating a dose dependency of NAM's photoprotection. These results highlight the potential for combining photoprotective compounds to enhance photoprotection. Plain Language Summary: Skin cancer is the most common type of cancer seen in the clinic. The amount of lifelong sun exposure and the degree of sunburns are important contributors to the development of skin cancer. Despite massive prevention campaigns promoting better sun habits by staying in the shade and applying sufficient sunscreen, skin cancer cases are still increasing. To address this, researchers are exploring different compounds for oral sun protection. In this study, we tested whether combining vitamin B3 (nicotinamide) with the well-known medication metformin or a known antioxidant called phloroglucinol could enhance its protection against sun-induced skin cancer. Hairless mice were given either nicotinamide alone or nicotinamide at a lower dose combined with either metformin or phloroglucinol through their drinking water and exposed to simulated sunlight 3 times per week to induce skin cancer. We show for the first time that mice treated with all three nicotinamide groups had a delay in skin cancer onset compared to sun-exposed control. Furthermore, we show that the nicotinamide and phloroglucinol combination provides the same sun protection as nicotinamide alone, whereas the combination with metformin did not. Notably, the nicotinamide combined with phloroglucinol provided a reduction in DNA damage, suggesting a better-suited mechanism of action for preventing skin cancer. Overall, the study indicates a potential strategy of combining compounds to enhance oral sun protection to prevent skin cancer. [ABSTRACT FROM AUTHOR]

This case highlights the consequences of unregulated, online-acquired topical treatments. This is exemplified by a 29-year-old woman who suffered from severe chemical burns to both hands after using a peeling solution purchased without a prescription. The absence of regulations allowed the sale of this product, leading to misuse and severe adverse effects. Such incidents show the urgent need for a regulation that would reduce the risks associated with online purchases of medical products. We need to register and make case reports whenever we see similar cases to ensure the authorities are aware of the extent of this problem. [ABSTRACT FROM AUTHOR]

Treatment-resistant actinic keratosis (AK) is of concern in clinical practice, often requiring retreatment. Microvascular assessments might help differentiate treatment-resistant from treatment-responsive AKs, enabling targeted treatment. Using dynamic optical coherence tomography, AK vascularization was investigated following daylight photodynamic therapy, comparing treatment-resistant with cleared AKs. AKs on face/scalp were graded according to the Olsen Classification Scheme and scanned with dynamic optical coherence tomography pre-treatment, and 3- and 12-months post-treatment. Employing dynamic optical coherence tomography, total vessel length, mean vessel length, mean vessel diameter, vessel area density, and branchpoint density were quantified. Thirty-eight patients with 62 AKs were enrolled, including 37 AK I, 18 AK II, and 7 AK III. Treatment-resistant AKs displayed a trend toward intensified vascularization compared with cleared AK at baseline (AKs I, II), suggested by higher total vessel length (median 144.0, IQR 104.3-186.6) and vessel area density (median 27.7, IQR 18.4-34.2) than in cleared AK (median 120.9, IQR 86.9-143.0 and median 22.9, IQR 17.3-26.8). Additionally, vascularization in treatment-resistant AK I--II appeared disorganized, with trends toward shorter mean vessel length (median 151.0, IQR 138.5-167.5) and increased branchpoint density (median 3.2, IQR 2.3-3.8) compared with cleared AK (median 160.0, IQR 152.0--169.3 and median 2.6, IQR 2.2-3.0). These findings suggest that dynamic optical coherence tomography holds potential to identify treatment-resistant AKs. [ABSTRACT FROM AUTHOR]

The efficacy of blue light therapy in dermatology relies on numerous clinical studies. The safety remains a topic of controversy, where potentially deleterious effects were derived from in vitro rather than in vivo experiments. The objectives of this work were (1) to highlight the nuances behind "colors" of blue light, light propagation in tissue and the plurality of modes of action; and (2) to rigorously analyze studies on humans reporting both clinical and histological data from skin biopsies with focus on DNA damage, proliferation, apoptosis, oxidative stress, impact on collagen, elastin, immune cells, and pigmentation. We conclude that blue light therapy is safe for human skin. It induces intriguing skin pigmentation, in part mediated by photoreceptor Opsin‐3, which might have a photoprotective effect against ultraviolet irradiation. Future research needs to unravel photochemical reactions and the most effective and safe parameters of blue light in dermatology. [ABSTRACT FROM AUTHOR]

Background & aims: Sleep disturbances are related to hepatic encephalopathy and hyperammonaemia in patients with cirrhosis. The circadian rhythm is regulated by light stimulation of the retina via melanopsin-containing ganglion cells. The study aimed to investigate whether induced hyperammonaemia affects the pupillary light response and sleep efficiency in patients with cirrhosis. Methods: The study was a single-blinded crossover trial including nine patients with cirrhosis. Sleep was evaluated by Pittsburgh Sleep Quality Index (PSQI) and monitored for twelve nights with wrist accelerometers and sleep diaries. On two experimental days, separated by one week, patients were randomized to ingest either an oral amino acid challenge (AAC) or an isocaloric glucose solution (GS). We measured pupillary light response, capillary ammonia, the Karolinska Sleepiness Scale (KSS), and two neuropsychological tests on both experimental days. Results: The patients had poor self-assessed sleep quality. The amino acid challenge led to a significant increase in capillary ammonia and KSS. The time spent in bed sleeping after AAC was longer and with a reduced movement index compared to baseline but not different from GS. We found no difference in the pupillary light response or neuropsychiatric tests when comparing the effect of AAC with GS. Conclusions: Patients with cirrhosis had impaired sleep quality. Induced hyperammonaemia led to increased sleepiness but had no acute effect on pupillary light response or the neuropsychiatric tests. Trial registration: Registration number: NCT04771104. [ABSTRACT FROM AUTHOR]

• The incidence of actinic keratoses is high and continuously increasing. • Effective and well-tolerable treatments are needed. • Sequential 5-FU and daylight PDT was compared with daylight PDT alone. • 5-FU+dPDT more effective than PDT monotherapy for large treatment areas. • 5-FU+dPDT resulted in high compliance and patient satisfaction. Daylight photodynamic therapy (dPDT) and topical 5-fluorouracil (5-FU) are each effective treatments for thin grade I actinic keratosis (AKs), but less so for thicker grade II-III AKs. Prolonged topical treatment regimens can be associated with severe skin reactions and low compliance. This study compares the efficacy of sequential 4 % 5-FU and dPDT with dPDT monotherapy for multiple actinic keratoses. Sixty patients with a total of 1547 AKs (grade I: 1278; grade II: 246; grade III: 23) were treated in two symmetrical areas (mean size 75 cm2) of the face or scalp, which were randomized to (i) 4% 5-FU creme twice daily for 7 days before a single dPDT procedure and (ii) dPDT monotherapy. Daylight exposure was either outdoor or indoor daylight. Twelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p<0.0001). For grade II AKs, the lesion response rate increased from 55 % with dPDT monotherapy to 79 % after 5-FU+dPDT (p<0.0056). Moderate/severe erythema was seen in 88 % 5-FU+dPDT areas compared to 41 % of dPDT areas two days after dPDT. Twelve weeks after treatment 75 % of the patients were very satisfied with both treatments. Sequential 5-FU and dPDT was more effective than dPDT monotherapy in the treatment of AKs, especially for grade II AKs. Local skin reactions were more pronounced after combination treatment, but no patients discontinued the treatment. The combination of 5-FU and dPDT is an effective treatment of large treatment areas with high compliance and satisfaction. [ABSTRACT FROM AUTHOR]

Introduction and objectives:This qualitative review of paradoxical hair growth, following professional treatments reviews, clarifies whether low fluence is the most probable cause of unwanted hair regrowth after at home light-based treatments.Materials and methods:The proposed causes of unexpected hair regrowth are examined, and our scientific understanding of absorption and scattering of light in turbid tissue is reviewed. Published reports of paradoxical hair growth are assessed.Results:Early laser hair removal studies failed to record the occurrence of hair induction despite the significant numbers of subjects treated. Neither published paradoxical hair growth studies following home-based laser or intense pulsed light (IPL) hair removal treatments, nor randomised or controlled studies documenting paradoxical hair growth following professional treatments could be found. Several authors directly proposed inflammatory response to be the primary cause of hair growth induction.Conclusions:It is unlikely that hair regrowth several centimetres or more away from the irradiated tissue can be attributed to the laser or IPL used. In many cases of paradoxical hair growth, other causes may be responsible for the unexpected hair growth. The primary cause of instances of ‘true’ paradoxical hair growth is probably limited to darker phototypes with one or more other characteristics including polycystic ovarian syndrome or other androgen hormonal irregularities following high energy treatments with the corresponding inflammatory sequelae. [ABSTRACT FROM PUBLISHER]