Treatment Protocols Research Articles

The Secret of Antibiofilm Agent for Burn Injury : A Systematic Review

Burn injuries remain to be a significant issue. The environmental condition in Indonesia contributes to the prevalence of diverse bacterial infection associated with different types of wounds, including burns. The biofilms production at the site of burn wounds significantly contributes to the ineffectiveness of burn treatment protocols. Hereby in this paper we discuss about the mechanism of antibiofilm and the novel therapy for the burn injury.  This study was classified as a systematic review approach. The compilation of references will be derived from journal articles obtained using search engines such as PubMed, Google Scholar, and EBSCO. Subsequently, the authors proceed to gather and reevaluate pertinent material and scholarly articles. The occurrence of biofilm is closely associated with burn injuries. These bacterial communities evoke antibiotic resistance, hence impeding the effectiveness of conventional treatment approaches. It is noteworthy that substantially 60% of burn-related mortality is attributed to biofilms. This condition has the potential to develop into a persistent wound, ultimately resulting in sepsis. The development of biofilm or invasive burn wound infection serves as a significant catalyst for the occurrence of sepsis. The administration of anti-biofilm drugs holds significant potential in this context as a proactive measure for reducing the worsening effects of burns. Conclusion : The utilization of anti-biofilm agents has the potential to serve as an innovative therapeutic approach for the treatment of burn wounds in the future. Further investigation is required to explore the potential outcome as well as adverse effects of this drug linked to its potency.

Comparison of Dentoalveolar Expansion with Clear Aligners by Using Two Different Treatment Protocols in the Early Mixed Dentition: A Retrospective Study

Objectives: To evaluate the effect of different expansion protocols on tooth movements during maxillary arch expansion with Invisalign First System® (IFS) in the mixed dentition. Materials and Methods: This study was conducted using digital models of 20 patients treated with sequential expansion (MFE, mean age: 7.88±0.60; 9 girls, 11 boys) and 20 patients treated with simultaneous expansion (SIE, mean age: 7.94±0.51; 12 girls, 8 boys) acquired before (T0) and after (T1) treatment. Maxillary parameters were measured on each model at T0 and T1. Mann Whitney U tests were used for comparisons between groups, and Wilcoxon tests were used for the analysis of intra-group. Results: In both groups, the greatest increase of maxillary arch width (AW) was determined at both the cusp tips and gingival levels of the upper first deciduous molars followed by the second deciduous molars and by the deciduous canines (p < 0.01). The lowest increase of AW was found in the at the permanent first molars (p < 0.01). Conclusion: Both protocols with IFS can be considered effective in patients in early mixed dentition. The greatest increase was detected at the level of the upper first deciduous molars, whereas the least increase was observed at the level of the first permanent molars. Key Words: Clear Aligners, Invisalign® First system, Mixed dentition

Analysis of Aetiological Agents in Infectious Endocarditis in the Central Military Emergency University Hospital “Dr. Carol Davila” Bucharest

Background: Infective endocarditis (IE) is a pathological condition caused by various microbial agents that can lead to severe complications affecting the heart. Accurate diagnosis is crucial for the effective management of patients with IE. Blood culture is the gold standard for identifying the primary infectious agents, which is a key factor in diagnosing IE using the modified Duke criteria. Objective: The main objective of this study was to investigate the distribution of the etiological agents of IE and the most common secondary diagnoses associated with it. Method: A total of 152 patients aged 23–95 years with a diagnosis of IE and proven etiology (through blood cultures or serological tests) were included in this study. Results: The most common etiological agent identified through blood tests was Enterococcus faecalis, which was detected in 39 patients (23.5%). Staphylococcus aureus was the second most common agent and was identified in 33 patients (19.9%), followed by Staphylococcus epidermidis, which was identified in 12 patients (13.1%). Nine patients (5.8%) had high levels of anti-Coxiella burnetti IgG phase I and II antibodies. Conclusions: IE is a leading cause of death in the Department of Infectious Diseases. Early and accurate diagnosis, along with interdisciplinary treatment, can significantly increase the chances of patient survival. Currently, Enterococcus faecalis and Staphylococcus aureus are the dominant etiological agents of IE, highlighting the need to revise protocols for prophylaxis, diagnosis, and initial treatment of this condition.

Addressing Challenges in Standardizing Helicobacter pylori Treatment Protocols: Importance and Review

Addressing Challenges in Standardizing Helicobacter pylori Treatment Protocols: Importance and Review

Pathogenetic strategies for addressing periodontal morphological and functional disorders in plaque-induced gingivitis

Relevance. Plaque-induced gingivitis represents the initial phase of periodontal diseases and a significant medical and social challenge within global healthcare frameworks, particularly prevalent among younger people.Demographics. This prevalence arises from its multifactorial etiology, complex developmental mechanisms, and notable pathogenetic features, most evidently microcirculatory disruptions leading to tissue hypoxia. Addressing these pathological conditions requires the development of novel diagnostic methodologies and therapeutic interventions to prevent further complications.Materials and methods. The study encompassed 54 subjects with an average age of 22.5 ± 1.7 years. The control group included 34 participants (GroupI), and the comparison group 20 participants (Group II). Group II received vacuum laser therapy in conjunction with Mexidol-based dressings, noted for their antihypoxant and antioxidant properties.Results. Evaluations conducted post-treatment indicated enhancements in both arterial and venous capillary functions. Amid the antioxidant and antihypoxant treatment regimen, capillary diameters were reduced to match those observed in the control group.Conclusion. Regimen implemented in this study was clinically and functionally effective in a combined treatment protocol involving vacuum laser therapy on periodontal tissues of plaque-induced gingivitis patients. This regimen is recommendable as a corrective measure for microcirculatory disturbances within the scope of managing inflammatory periodontal diseases.

Ankle presentations in Awka, Nigeria; Treatment methods and outcome

Introduction: The ankle joint, integral to dynamic movement, is prone to a variety of pathologies due to its complex structure and the substantial load it bears during activities such as sprinting, where it can carry up to thirteen times the body's weight. Stability is maintained through passive components like ligaments and bony contours, as well as dynamic forces, including muscle action. Injuries, which can be categorized by systems like the Danis-Weber AO and Lauge-Hansen classifications, are common in diverse settings and can lead to conditions like post-traumatic osteoarthritis. This study explores the prevalence, management, and outcomes of ankle injuries in an orthopaedic hospital setting, aiming to enhance understanding and treatment approaches for these conditions. Methodology: This prospective study analyzed all ankle cases at an orthopaedic hospital in Awka, Nigeria, from 2017 to 2023. Patients were evaluated and diagnosed via history, physical examinations, and investigations, including X-rays classified by the Danis-Weber system. Treatments ranged from surgery, including ORIF and arthrodesis, to casting for undisplaced fractures. Result: This study found the mean age of patients presenting with ankle injuries to be 41.44 years, affecting a wide demographic from 10 to 78 years. Males comprised 60.6% of the cases, and civil servants, who constituted 33.3%, were predominantly affected. The major causes were road traffic accidents (45.5%) and falls (33.3%). Ankle injuries, primarily right bimalleolar fractures, were common and involved significant trauma history. Treatments included ORIF, arthrodesis, and casting, with a high success rate of 97% inpatient recovery and satisfaction, indicating effective treatment protocols for various ankle pathologies, including closed and open injuries. Conclusion: The study illustrates that ankle injuries, predominantly resulting from road traffic accidents and falls, affect a diverse demographic across all ages and occupations, with a majority being male and often involving previous trauma, with closed injuries being the most common and effectively treated primarily through ORIF.

Complex elbow fracture-dislocations- what factors are associated with a poor post-operative outcome?

Despite standardized treatment algorithms, patients with complex elbow fracture-dislocation frequently suffer from poor post-operative elbow function leading to reduced quality of life. Up to now, there is no valuable data regarding risk factors that lead to poor post-operative outcome after surgical reconstruction of complex elbow fracture-dislocations. From 06/2010 to 12/2020 134 patients (51.3 ± 15.1 years, 44% women) undergoing surgical treatment of complex elbow fracture-dislocations could be included in this study. Follow-up period was 4.4 years (SD 2.5). All patients were clinically evaluated for elbow movement, elbow stability and common elbow scores (MEPS, OES, DASH-Score). Potential risk factors for poor post-operative outcome were identified using bi- and multivariate analyses. Overall good post-operative outcome has been achieved, mean MEPS was 88.8 ± 17.6. Post-operative complications occurred in 31.3% of the cases, while 25.4% required surgical revision. Patients with transolecranon dislocation fractures showed the significantly worst functional outcomes (p = 0.01). In addition, it has been shown that a patient's age of more than 70 years (OR = 10, p = 0.003) and a BMI of more than 35kg/m2 (OR = 7.6, p = 0.004) are independent risk factors for a poor post-operative outcome. In contrast, gender and time to surgery showed no significant influence on post-operative outcome. In most cases, good post-operative functional results can be achieved using standardized treatment protocols. However, complication and revision rates remain high. Patients older than 70 years of age or with a BMI over 35kg/m2 are at risk for an inferior outcome and require close follow-up monitoring.

The importance of Neuro-Cognitive Processing to the Understanding and Treatment of Child PTSD

Abstract Basic research and current clinical practice have revealed the difficulty in separating/connecting cognition and emotion and their respective localizations in the brain. Regarding Post-Traumatic Stress Disorder (PTSD), emotions (usually fear) cause a cascade of symptoms, including those impacting several cognitive processes. And it is often considered that relieving the emotional upset associated with PTSD will also improve related cognitive functioning. While it is often assumed that the relationship of emotion, cognition and PTSD is unidirectional, this may not necessarily be the case. The present article aims to describe the complex relationship between emotion and cognitive processes in those with PTSD and suggests an important role for executive functioning as a modulator of the emotion/cognition relationship, as well as the latter’s importance as a contributor to the successful treatment of PTSD. The paper concludes by stressing the importance of assessing cognitive processes in standard treatment protocols evaluating patients with PTSD and highlights the potential benefits of training executive functions as part of PTSD therapy. Keywords: PTSD, Cognitive processes, Emotion, Executive function, Neuropsychology.

CAR-T CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA

The treatment outcomes of patients with chronic lymphocytic leukemia (CLL) have considerably improved with the introduction of targeted therapies based on Bruton kinase inhibitors (BTKIs), venetoclax, and anti-CD20 monoclonal antibodies. However, despite these consistent improvements, patients who become resistant to these agents have poor outcomes and need new and more productive therapeutic strategies. Among these new treatments, a potentially curative approach consists of the use of chimeric antigen receptor T (CAR-T) cell therapy, which achieved remarkable success in various B-cell malignancies, including B-cell Non-Hodgkin Lymphomas (NHLs) and B-acute lymphoblastic Leukemia (ALL). However, although CAR-T cells were initially used for the treatment of CLL, their efficacy in CLL patients was lower than in other B-cell malignancies. This review analyses the possible mechanisms of these failures. It highlights some recent developments that could offer the perspective of the incorporation of CAR-T cells in treatment protocols for relapsed/refractory CLL patients. Keywords: Chronic Lymphoid Leukemia; CLL; CAR-T Cells; Relapsed/resistant CLL:

ОСОБЕННОСТИ ЭНДОДОНТИЧЕСКОГО ЛЕЧЕНИЯ C УЧЕТОМ ВЫЯВЛЕННОЙ CANDIDA ALBICANS В СИСТЕМЕ КОРНЕВЫХ КАНАЛОВ

The subject of the study was to study the properties of basic means for irrigation and physical methods of influencing the microflora of the root canal system against identified Candida Albicans. The purpose of the work was to review and analyze the features of endodontic dental treatment, taking into account the identified Candida Albicans in the root canal system. A search was conducted in domestic publications and foreign sources for studies containing information on various methods of influencing root canal biofilms during endodontic treatment. A comparison was made of the activity of various irrigants and physical methods of root canal treatment in relation to the identified microflora containing bacteria such as yeast-like fungi of the genus Candida and others. Sodium hypochlorite solution (NaOCl) is a mandatory antiseptic agent included in the recommended endodontic treatment protocol used in modern dentistry. To achieve a successful result, we consider it necessary to perform high-quality mechanical treatment of root canals, competent selection of irrigants, as well as the use of additional physiotherapeutic methods (ultrasound or laser technologies). A bacterioscopic examination of the contents of the root canals was carried out for the presence of yeast-like fungi of the genus Candida. A temporary exposure of a suspension of the drug “Fluconazole” on a paper point was introduced into the root canals at the first stage of endodontic treatment, and the drug “Fluconazole” was prescribed orally at a dose of 150 mg on the first day. Then, in the absence of exudate or odor in the root canals, as well as confirmation by bacterioscopic examination of the absence of yeast-like fungi of the genus Candida, the root canals were filled with permanent material. But despite following all clinical recommendations, in some cases it is not possible to achieve the required effect due to the resistance of biofilms containing Candida albicans, Prevotella melaninogenica, Enterococcus faecalis, Bacteroides fragelis in the root canal system to the effects. Despite the wide variety of endodontic treatment methods and drugs for influencing representatives of the root canal microflora, it is not always possible to achieve complete elimination of biofilm during irrigation and medicinal or physical influence on them. It is especially important to look for ways to modify treatment and make it easier to use and accessible in order to avoid subsequent complications.

МЕТОДИКА МЕДИЦИНСКОГО СОПРОВОЖДЕНИЯ ПАЦИЕНТОВ ПОСЛЕ ПРОВЕДЕНИЯ ДЕНТАЛЬНОЙ РЕПЛАНТАЦИИ

Modern dentistry is aimed at using minimally invasive interventions to preserve dentition. This fact determines the need for wider use of various types of tooth-preserving operations. In modern conditions, tooth-preserving operations are increasingly being carried out with a predictable successful outcome. Treatment of dental trauma involves complex endodontic or surgical treatment protocols. An important aspect in the rehabilitation of dental injuries is the development of clear diagnostic tactics both at the initial appointment and at all stages of treatment. We observed 127 patients from 2012 to 2022 with diagnoses: complete, incomplete tooth dislocation, uncomplicated or complicated by fractures of the coronal part of the teeth, men and women aged 18 to 40 years. The first group consisted of 66 people with traumatic dislocations of teeth, who sought medical help within 24 hours after the injury, who underwent tooth replantation surgery, endodontic treatment, a complex treatment developed aimed at stopping an acute inflammatory reaction of a post-traumatic nature, and carrying out the necessary splinting measures. The second group consisted of 61 people with traumatic dislocations of teeth who sought medical help after 24 hours or later. Patients in each group were divided into subgroups; in the control subgroups, traditional treatment and rehabilitation after dental replantation were carried out; in the main subgroups, the technique we developed using M-Chip nanomatrices and LED radiation was used. All patients underwent macrohistochemical examination and measurement of dentogingival attachment using a periodontal probe. The results of a macrohistochemical study 7 days after replantation showed that in groups 1b and 2b, whose patients received complex treatment according to the developed method, the area of inflammation of the mucogingival complex was smaller than in patients in groups 1a and 2a, who were treated according to the traditional method. Results of probing of the dentogingival attachment found that in groups 1b and 2b, whose patients received complex treatment using the developed method, the dentogingival attachment corresponds to normal indicators of a healthy periodontal complex than in patients in groups 1a and 2a, who were treated using the traditional method. The inclusion in the complex of rehabilitation measures after dental replantation surgery of drugs that have antiseptic, reparative, hemostatic and immunoadjuvant effects, using LED radiation, increases the effectiveness of these measures by 2-3 times.

Adjuvant immune checkpoint inhibitor therapy may benefit pediatric patients with stage III melanoma and sentinel lymph node positivity: a case series

Melanoma is the most common skin cancer in children. While the current literature establishes treatment protocols for adult-type melanoma, very few pediatric-specific studies exist, and children are often excluded from melanoma clinical trials2. We report a case series of 23 pediatric patients aged 2–20 years old diagnosed with melanoma at the University of Rochester Medical Center between 1/1/2011 and 1/1/2022. 9/23 patients were Stage III; all patients underwent wide local excision and 9 received adjuvant therapies. 2/23 (8.7%) patients had recurrence of their malignancy after therapy while 21/23 (91.3%) remained without disease progression; 1 patient died from unknown cause, but the rest are alive and currently without disease. All patients whose initial therapy included nivolumab in addition to wide local excision did not have recurrence or progression of their disease. This case series highlights trends in the presentation, treatment, and outcomes of pediatric melanoma; however, additional multi-center studies are needed to establish the clinical utility of such features in pediatric melanoma.

The Use of Quantum Stem Cell Therapy for Autoimmune Diseases Treatment

This qualitative descriptive study explores the effectiveness of quantum stem cell therapy in addressing autoimmune diseases, with a specific focus on immune modulation and tissue regeneration. Conducted at the Vinski Regenerative Center, the study involved two female patients, aged 53 and 59, who underwent repeated stem cell injections over a specified period. Patient data, encompassing demographic information and disease characteristics, were collected through comparative literature reviews and laboratory analyses. Preliminary findings reveal promising therapeutic outcomes, manifesting as improvements in symptoms such as weakness, joint pain, skin rashes, and fever. Stem cell therapy exhibited potential for immune suppression and tissue repair, thereby offering a novel avenue for managing autoimmune diseases. Further research is imperative to refine treatment protocols and elucidate underlying mechanisms, ultimately enhancing patient care and outcomes in autoimmune disease management.

The Efficacy of Multivitamin, Vitamin A, Vitamin B, Vitamin C, and Vitamin D Supplements in the Prevention and Management of COVID-19 and Long-COVID: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials.

This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023 to identify randomized clinical trials comparing data on the effects of vitamin supplementation(s) versus placebo or standard of care on the two conditions of interest. Inverse-variance random-effects meta-analyses were conducted to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality between supplemented and non-supplemented individuals. Overall, 37 articles were included: two regarded COVID-19 and long-COVID prevention and 35 records the COVID-19 management. The effects of vitamin D in preventing COVID-19 and long-COVID were contrasting. Similarly, no conclusion could be drawn on the efficacy of multivitamins, vitamin A, and vitamin B in COVID-19 management. A few positive findings were reported in some vitamin C trials but results were inconsistent in most outcomes, excluding all-cause mortality (RR = 0.84; 95% CI: 0.72-0.97). Vitamin D results were mixed in most aspects, including mortality, in which benefits were observed in regular administrations only (RR = 0.67; 95% CI: 0.49-0.91). Despite some benefits, results were mostly contradictory. Variety in recruitment and treatment protocols might explain this heterogeneity. Better-designed studies are needed to clarify these vitamins' potential effects against SARS-CoV-2.

A Systematic Review of Efficacy and Safety of Plasma-Derived von Willebrand Factor/Factor VIII Concentrate (Voncento) in von Willebrand Disease.

For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis regimens. This systematic literature review was conducted to evaluate the efficacy, consumption, and safety of plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento/Biostate) for the treatment of patients with any inherited VWD type. An electronic search was conducted in MEDLINE and Cochrane Library databases on VWD therapies. All retrieved publications were assessed against predefined inclusion/exclusion criteria following the Cochrane group recommendations. Associated pharmacovigilance data were collected across the same time period. Eleven publications from eight study cohorts were identified for data retrieval. All were from multicenter studies and included both pediatric and adult patients. Eight publications included evaluations of the efficacy of pdVWF/FVIII for on-demand treatment, eight included long-term prophylactic treatment, and eight included surgical prophylaxis. Treatment protocols and VWF administration methods differed between studies, as did safety evaluations. The clinical response was rated as excellent/good for on-demand treatment in 66 to 100% of nonsurgical bleeds, 89 to 100% in the treatment of breakthrough bleeds during long-term prophylaxis treatment, and hemostatic efficacy in surgical procedures was 75 to 100%. Pharmacovigilance data confirmed a low incidence of adverse events in treated patients. This review provides a comprehensive summary of studies that evaluated the use of pdVWF/FVIII in VWD demonstrating the long-term effectiveness and safety of this pdVWF/FVIII across all ages, types of VWD, and treatment settings.

Changes in masticatory performance and bite force after treatment with mandibular overdentures retained by four titanium-zirconium mini implants: One-year randomised clinical trial.

This prospective study is part of a randomised clinical trial and reports the changes in masticatory performance (MP) and bite force, and explores their influential factors, 1 year after the provision of mandibular overdentures retained by four titanium-zirconium mini implants. Edentulous patients received conventional complete dentures, followed by placement of four mini implants (Straumann® Mini Implant System) in the anterior mandible and converting the conventional prosthesis into a mandibular overdenture. Treatment protocols were randomised using a 2×2 factorial design combining different surgical (flapped vs. flapless) and loading (immediate vs. delayed) protocols. MP was assessed using a two-colour mixing ability test and a colorimetric analysis to measure the level of colour mixing (Variance of Hue-VoH). Maximum voluntary bite force (MBF) was measured by a digital gnathodynamometer in the posterior and anterior regions. Sex, age, surgical and loading protocols and ridge morphology were tested as independent variables. MP and MBF tests were performed at baseline (pre-treatment) and the 3-, 6- and 12-month after implant loading. Descriptive statistics, independent t-test, and linear mixed-effect model (LMM) regression were used for data analysis. Seventy-four participants were assessed and 73 completed the 1-year follow-up. Statistically significant improvements in functional parameters were observed in all follow-up periods compared to baseline (p < .001). The flapless protocol was associated with higher improvement in MP at the 3-month follow-up (p = .004), while less resorbed ridges were associated with better MP (p = .038) and higher MBF (p < .001). The mandibular overdenture protocol using four titanium-zirconium mini implants was effective in improving MP and MBF of edentulous patients, compared to pre-treatment values. The findings also suggest that improvements in chewing function and bite force are impacted by clinical factors since better outcomes were observed for flapless surgeries and less resorbed edentulous ridges. ClinicalTrials.Gov ID NCT04760457.

Delayed Puberty and Management of Treatment.

Delayed puberty is defined as the lack of development of secondary sex characteristics in childhood. Based on a review of the literature, delayed puberty can be divided into three main categories: (i) hypergonadotropic hypogonadism (congenital and acquired), (ii) permanent hypogonadotropic hypogonadism (congenital and acquired), and (iii) transient hypogonadotropic hypogonadism [constitutional delay of growth and puberty (CDGP) and functional hypogonadotropic hypogonadism (FHH)]. CDGP is the most common cause of hypogonadism in both males and females, accounting for 60% and 30% respectively. Testosterone is the primary treatment for male hypogonadism, while estrogen and progesterone are used for female hypogonadism. However, in recent years, physiological induction therapy protocols such as human chorionic gonadotropin (hCG) monotherapy, hCG + Follicle-stimulating hormone combined therapy, and gonadotropin releasing hormone infusion have been recommended for the treatment of hypogonadotropic hypogonadism to increase long-term fertility success. There is no clear consensus on treatment protocols for physiological induction treatment and its effect on fertility. This review will discuss the clinical approach to hypogonadism, as well as traditional and physiological induction protocols.

Care home staff interventions to optimise pain assessment and management in people with advanced dementia in long-term care settings: a systematic review

Abstract Introduction As a person’s dementia symptoms worsen, they become increasingly frail and dependent on others for support,[1] which often necessitates moving into long-term care (LTC). Pain is often poorly recognised and undertreated in people with advanced dementia.[2] Aim To identify and evaluate the effectiveness of care home staff interventions involving pain assessment and management in people with advanced dementia in LTC settings. Methods This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022355487). Nine databases (Medline, Scopus, The Cochrane Library, EMBASE, Web of Science, International Pharmaceutical Abstracts, PsycINFO, CINAHL, World Health Organisation International Clinical Trials Registry Platform) were searched. The search strategy was developed in Medline and adapted as appropriate for the other databases; it comprised the following search terms: ‘dementia’, ‘Alzheimer’s disease’, ‘pain assessment’, ‘pain management’, ‘pain intervention’, ‘care home’, and ‘nursing home’. The selection of studies was limited to randomised controlled trials (RCTs) in which ≥50% of participants had advanced (moderate-severe) dementia and published in English. Electronic databases were searched from date of inception to May 2023. Two reviewers independently assessed potentially relevant articles for inclusion, completed data extraction and assessed risk of bias using the Cochrane Risk of Bias (RoB) 2.0 tool. A third reviewer was consulted when consensus could not be reached. A narrative analysis was undertaken due to the heterogeneity of outcome measures. Results In total, 3504 articles were identified, with 998 records remaining after duplicate removal. This left 2456 studies for title/abstract screening, and 22 full-text studies were assessed for eligibility; five studies met the inclusion criteria. A total of 1363 participants (mean age 83-88 years) and 123 care homes were included in the studies. The studies reported that these interventions were shown to be effective compared to control groups: the Pain recognition and Treatment (PRT) protocol in China, regular use of the PACSLAC pain assessment tool in Canada, the use of a Comprehensive Observational Pain Management Protocol in Hong Kong, the COSMOS intervention in Norway, and the STA OP stepwise multidisciplinary intervention in the Netherlands. Primary outcomes concerning pain scores measured by PACSLAC (n=2 studies), PAINAD (n=2 studies), and MOBID-2 (n=1 study) showed a statistically significant decrease. Secondary outcomes measured included several clinical outcomes associated with pain, depression, presence of neuropsychiatric symptoms and nursing staff stress. Four of the included studies were judged to be at ‘some concerns of bias’ according to RoB 2.0, due to unclear information in two or more domains (randomisation process, deviations from intended interventions, and measurement of the outcomes); one study was judged as having a ‘low risk of bias’. Conclusion The use of pain assessment tools decreased pain scores in people with advanced dementia in LTC. A limitation of this review is the exclusion of non-English language studies. Further, the clinical and methodological heterogeneity of included studies made a quantitative comparison difficult, thus, the findings are based on narrative analysis.

Neoadjuvant radiotherapy in ER+, HER2+, and triple-negative -specific breast cancer based humanized tumor mice enhances anti-PD-L1 treatment efficacy.

Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological "cold" breast cancers by neoadjuvant irradiation into their "hot" variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced "in-situ vaccination", especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype -specific manner. According to the "bench to bedside" principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.

Importance of treating acne sequelae in skin of color: 6-month phase IV study of trifarotene with an appropriate skincare routine including UV protection in acne-induced post-inflammatory hyperpigmentation.

Acne-induced hyperpigmentation (AIH) may accompany acne vulgaris (AV) inflammation in all skin phototypes. Trifarotene has shown depigmenting properties in vivo. This study evaluated trifarotene plus skincare because it is increasingly recognized that holistic AV management should include skincare and treatments. This is a phase IV double-blind, parallel-group study of patients (13-35 years) with moderate AV and AIH treated with trifarotene (N = 60) or vehicle (N = 63) plus skincare regimen (moisturizer, cleanser, and sunscreen) for 24 weeks. Assessments included the AIH overall disease severity (ODS) score, post-AV hyperpigmentation index (PAHPI), exit interviews, photography, and acne assessments. Standard safety assessments were included. Trifarotene 50 μg/g cream improved significantly from baseline in ODS score versus vehicle (-1.6 vs. -1.1, P = 0.03) at Week 12, but scores were comparable between groups at Week 24 (primary endpoint). Trifarotene had a better reduction in PAHPI score at Week 24 (-18.9% vs. -11.3% vehicle, P < 0.01). Lesion count reductions were higher with trifarotene at Week 12 versus vehicle (P < 0.001) and at Week 24 (P < 0.05), as were IGA success rates versus vehicle at Weeks 12 (P < 0.05) and 24 (P < 0.05). Patients agreed that the skincare regimen contributed to less irritation, making treatment adherence easier. Photography showed improvements in pigmentation and erythema across all skin types. AEs were more common in the vehicle group versus trifarotene (30.2 vs. 16.7%, respectively). In all skin phototypes, there was more rapid improvement in the ODS and PAHPI scores with trifarotene by Weeks 12 and 24, respectively. The combination of trifarotene and skincare correlated with high patient satisfaction and adherence to the treatment protocol.