Malignant transformation of oral lichen planus: where are we now?

BACKGROUND: Oral lichen planus (OLP) is a very prevalent disease whose main clinical feature is the appearance of white hyperkeratotic reticular lesions, which may or may not be accompanied by erosive and/or atrophic lesions, among others. One of the most relevant aspects of the process is its current consideration as an oral potentially malignant disorder (OPMD), although this is currently the subject of considerable controversy. MATERIAL AND METHODS: A review of the literature was carried out in order to critically analyze the controversies surrounding the consideration of OLP as an OPMD, where they originate from and the available evidence that has led to the conclusion that OLP patients are at risk of developing oral cancer. RESULTS: The controversies over the definitive acceptance of OLP as an OPMD were classified as controversies related to the lack of widely accepted diagnostic criteria for OLP; controversies related to histopathological aspects of OLP and the presence of epithelial dysplasia as a diagnostic exclusion criterion; and controversies related to clinical aspects of OLP (which in turn were subclassified into: controversies on how to interpret reticular lesions in OLP, on the nature of the white plaques that appear in OLP; on the changing character of reticular lesions in OLP; and on the criteria for accepting a case as a true malignant OLP). Furthermore, evidence to justify the acceptance of OLP as an OPMD was in depth reviewed, including the molecular evidence, evidence from research studies with the highest evidence design -systematic reviews and meta-analyses-, and evidence from case series reporting strong results. CONCLUSIONS: This paper presents the reasons for the controversies as well as the evidence that allows us to accept that OLP behaves as an OPMD.

Clinicopathologic characteristics of young patients with lip squamous cell carcinoma: a retrospective study.

BACKGROUND: This retrospective study investigates the clinicopathological features and outcomes of young and elderly patients diagnosed with lip squamous cell carcinoma (LSCC). MATERIAL AND METHODS: Data from LSCC patients from Dr. Luiz Antonio Hospital in Natal, Brazil (2000-2015) were analyzed, grouping individuals below 40 and above 60 years old. Demographics, lifestyle habits, clinicopathologic characteristics, and treatment outcomes were examined using descriptive statistics, Chi-square and Fisher's tests, and Kaplan-Meier survival analysis. RESULTS: A total of 47 patients was analyzed, being 20 younger and 27 older, finding significant age-related differences (p = < 0.0001). Although in both groups the tumor was more common in males, older patients had a higher rate of females (29.6%) (p=0.0358) and smoking (70.4%) (p = 0.0043) and underwent more modalities of treatments (p = 0.0027). There were no significant differences in the other analyzed clinicopathologic factors, and survival rates did not differ significantly, though younger patients showed slightly better survival metrics in univariate analysis. CONCLUSIONS: LSCC exhibits some distinct clinicopathological features across different age groups, with significant differences in treatment modalities and progression rates. Age-specific approaches may be required to optimize treatment outcomes.

Efficacy of bone morphogenetic protein in comparison with autogenous bone in regeneration of ameloblastoma bone defects. A systematic review.

BACKGROUND: To evaluate the evidence comparing bone morphogenetic proteins (BMPs) and autogenous bone grafts (ABGs) for regenerating bone defects from ameloblastoma. MATERIAL AND METHODS: An electronic search was performed in PubMed and Scopus from October to December 2023, supplemented by manual searches and review of relevant study reference lists. Cohen's kappa was calculated to assess the interrater reliability between two independent investigators. The methodological quality and risk of bias of the selected articles was assessed using the JBI checklist for case series and the NOS for observational studies. RESULTS: Nine studies met the inclusion criteria and were selected for the qualitative synthesis. Cohen's kappa (κ) value resulted in 98.21% agreement. A total of 229 participants were included. The BMPs were evaluated in five studies, and four evaluated the ABGs. The BMPs has been tested in 25.76% of the patients, while ABGs were studied in 74.24%. In order to evaluate the final result of regeneration, all the studies based their analysis on postoperative questionnaires, radiographical (CBCT and/or panoramic) and/or clinical examination. The results showed a higher regeneration success rate in the studies where the BMPs was used. CONCLUSIONS: Considering the limitations of the studies and the review, it has been shown that BMPs may yield favorable outcomes in terms of bone regeneration, as compared with ABGs.

Implications of p53 protein upregulation in oral lichen planus: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis qualitatively and quantitatively analyzes the current evidence on the implications of p53 upregulation in oral lichen planus (OLP) assessed by immunohistochemical techniques, in order to identify molecular mechanisms involved in the behavior of OLP as an oral potentially malignant disorder. MATERIAL AND METHODS: We searched MEDLINE/PubMed, Embase, Web of Science and Scopus for studies published before February-2024. We critically assessed the methodological quality of primary-level studies and performed meta-analyses. RESULTS: Twenty-four individual studies met the inclusion criteria, comprising 721 OLP samples, in which the expression of p53 was analyzed through immunohistochemistry. Most OLP displayed p53 protein upregulation (pooled proportion [PP]= 66.76%, 95%CI=54.84-77.76). Regarding the magnitude of association analysis, oral squamous cell carcinoma (OSCC) cases showed a significantly higher frequency according to p53 expression in comparison to OLP (OR=2.79, 95%CI=1.84-4.24; p<0.001); while, OLP exhibited a significantly higher frequency for p53 expression in comparison to healthy controls (OR=5.70, 95%CI=2.90-11.19; p<0.001). CONCLUSIONS: In conclusion, the present study demonstrates the frequent p53 protein upregulation in patients with OLP, which is probably indicating an antitumor response in an epithelium whose cells are under cellular stress and at risk of cancer.

Outcomes from the International Society of Nephrology Haemolytic Uraemic Syndromes International Forum.

The haemolytic uraemic syndromes (HUS) are a heterogeneous group of conditions only some of which are mediated by complement (CaHUS). We report the outcome of the 2023 International Society of Nephrology HUS International Forum where a global panel of experts considered the current state of the art, identified areas of uncertainty, and proposed optimal solutions. Areas of uncertainty and areas for future research included: the nomenclature of HUS; novel complement testing strategies; identification of biomarkers; genetic predisposition to aHUS; optimal dosing and withdrawal strategies for C5 inhibitors; treatment of kidney transplantation recipients; disparity of access to treatment; and the next generation of complement inhibitors in CaHUS. The current rationale for optimal patient management is described.

Hypoxic burden and sleep hypoventilation in obese patients.

INTRODUCTION: Novel biomarkers of hypoxic load have emerged, as sleep apnea-specific hypoxic burden which provides more precise assessment of intermittent hypoxemia severity. Our main objective was to assess the potential benefit of hypoxic burden to identify obesity-related sleep hypoventilation. We hypothesized that hypoxic burden may help diagnose obesity-related sleep hypoventilation better than usual sleep respiratory measures (i.e., apnea-hypopnea index (AHI), mean SpO2, time with SpO2 < 90 %). METHODS: This retrospective study was conducted from June 2022 to October 2023 at the University Hospital of Rouen, France. All consecutive obese patients (BMI ≥30 kg/m2), adults, with no other respiratory or neurological diseases who underwent a polysomnography or polygraphy with concomitant capnography were included. Sleep hypoventilation was defined according to American Academy of Sleep Medicine criteria based on transcutaneous CO2 monitoring (PtcCO2). Diagnostic performance of sleep-related respiratory measures i.e., sleep apnea-specific hypoxic burden, apnea-hypopnea index (AHI), mean SpO2, time with SpO2 < 90 % was evaluated using Receiver Operating Characteristic (ROC) curves. Correlations between sleep-related respiratory measures were assessed by a Spearman correlation matrix. RESULTS: Among 107 obese patients with analyzed capnography, 37 (35 %) had sleep hypoventilation. Patients were 53 ± 14 years old, mean BMI = 38 ± 6 kg/m2, mean AHI = 26.5 ± 25/h, mean hypoxic burden = 67 ± 109 %min/h, mean SpO2 = 91.5 ± 3 %, mean time with SpO2<90 % = 19.4 ± 28 %, mean PtcCO2 = 6.2 ± 0.7 kPa. A low positive correlation was found between hypoxic burden and mean PtcCO2 (r = 0.4, p < 0.001). Multivariate logistic regression model explaining sleep hypoventilation was insufficient with area under ROC curve of hypoxic burden estimated at 0.74 (95 % CI 0.65 to 0.84). CONCLUSION: Hypoxic burden has low correlation with transcutaneous CO2 pressure and a low ability to diagnose obesity-related sleep hypoventilation.

Targeting TGF-ß signaling, oxidative stress, and cellular senescence rescues osteoporosis in gerodermia osteodysplastica.

GORAB is a key regulator of Golgi vesicle transport and protein glycanation. Loss of GORAB function in gerodermia osteodysplastica (GO) causes shortening of glycosaminoglycan chains, leading to extracellular matrix disorganization that results in wrinkled skin, osteoporosis and elevated TGF-ß signaling. In this study, we investigated the role of TGF-ß-signaling, oxidative stress, and resulting cellular senescence in the osteoporosis phenotype of GO. Treatment of GorabPrx1 conditional knockouts with the TGF-ß neutralizing antibody 1D11 rescued the trabecular bone loss, indicating that TGF-ß overactivation causes osteoporosis in GO. Using an inducible knockout system, we demonstrated that TGF-ß dysregulation was not a cell-intrinsic effect of GORAB inactivation, but a consequence of a disorganized extracellular matrix. Enhanced TGF-ß signaling caused elevated Nox4 expression in GorabPrx1 mutants and in GO patients' fibroblasts, resulting in overproduction of mitochondrial superoxide. The resulting oxidative stress was detected in GORAB null cells and also in wildtype bystander cells. The same effect was observed in zebrafish after TALEN-mediated gorab inactivation, indicating that the pathway is evolutionarily conserved. Treating GorabPrx1 mutants with the antioxidant N-acetylcysteine ameliorated the osteoporosis phenotype. TGF-ß induced oxidative stress coincided with accumulation of DNA damage and elevated expression of senescence markers. Inactivation of Cdkn2a in the GorabPrx1 rescued the osteoporosis phenotype. Reduced colony formation and altered subpopulations of bone marrow stromal cells were normalized upon inactivation of Cdkn2a, thus further demonstrating the relevance of cellular senescence in the pathogenesis. Our results shed light on the causative role of a TGF-ß-Nox4-senescence axis and therapeutic strategies for GO.

A case series of intermittent nucleoside analogue-based (NA) regimen to maintain HBV virological suppression in coinfected HBV/HIV patients with suppressed viremia.

OBJECTIVE: To describe the efficacy of intermittent nucleoside analogue-based (NA) regimen to maintain HBV virological suppression in HBV/HIV-1 patients. METHODS: Conducted between 2014 and 2023, this observational retrospective study included all HBV (positive AgHbs)/HIV-1 coinfected patients with HIV RNA ≤ 50 cp/mL and HBV DNA ≤ 25 UI/mL who were switched to an intermittent (<7/7 days(D)) TDF or TAF-containing antiretroviral (ART) regimen. The primary outcome was the HBV virological success rate (SR) (proportion of patients with HBV pVL < 25 UI/mL) at W48. RESULTS: Among 501 HBV/HIV-1 patients, 19(3.7 %) had switched to an intermittent NA-containing regimen that included TDF/FTC or TDF/3TC or TAF/FTC or TDF alone administered 5D-a-week(n = 7), 4D-a-week(n = 7) or 3D-a-week(n = 5). HBV virological success rates were 100 % [95 %CI 82.3-100] and 100 %[95 %CI 80.5-100] at W48 and W96(n = 17), respectively; with no viral HBV or HIV rebound (61.8 months (32.4-70.3) of follow-up). CONCLUSION: This case series shows the potential for intermittent NA-containing regimens to maintain long-term control of HBV replication among suppressed HBV/HIV-1 patients.

MSKI reduction strategies: evidence-based interventions to reduce musculoskeletal injuries in military service members.

Musculoskeletal injuries (MSKI) are one of the biggest challenges for military services globally, contributing to substantial financial burdens and lost training and working days. Effective evidence-based intervention strategies are essential to reduce MSKI incidence, and research has shown the positive effect of both nutritional interventions and physical training (PT) interventions on reducing MSKI incidence. Levels of vitamin D metabolites have been associated with MSKI and bone stress fracture risk, while calcium and vitamin D supplementation has been shown to reduce the incidence of stress fractures during military training. Protein and carbohydrate supplementation during arduous military training (high volume, high intensity) has also been shown to reduce MSKI risk and the number of limited/missed duty days. PT has played a key role in soldier development to meet the occupational demands of serving in the armed forces. Paradoxically, while PT is fundamental to enhancing soldier readiness, PT can also be a major contributor to MSKI; emerging evidence suggests that the nature of the PT being performed is a risk factor for MSKI. However, strategies like reducing training load and implementing PT programmes using evidence-based training principles can reduce MSKI incidence among military service members by 33-62%, and reduce the financial burdens for military services. This review provides a summary of effective MSKI reduction interventions and provides strategies to enhance the success and adoption of such interventions.

Synchronous cemento-ossifying fibromas: a systematic review.

BACKGROUND: This systematic review aimed to incorporate published data regarding synchronous cemento-ossifying fibromas (COF), with an analysis of their demographic and clinicopathological characteristics. MATERIAL AND METHODS: Case reports and case series of synchronous COF were searched in PubMed, Web of Science, Scopus, EMBASE, and LILACS according to the PRISMA (2020) statement. Also, a manual search was carried out and the grey literature was assessed. A descriptive statistical analysis was performed. RESULTS: Nineteen studies comprising 20 cases of synchronous COF were included. The mean age at diagnosis was 35 years (±13.8), with a predominance of female patients (n=12/60%). In 13 cases (65%) the mandible and the maxilla were affected simultaneously. In two cases (10%) first-degree relatives (parents or siblings) had been previously diagnosed with COF. The diagnostic hypotheses were reported in 8 cases (40%), with florid cemento-osseous dysplasia, ameloblastic fibroodontoma, calcifying cystic odontogenic tumor, osteoma and cementoblastoma being cited in the differential diagnosis. Among the cases with details about management (n=17), eleven were treated by surgical enucleation and/or excision (64.7%). Follow-up was provided for 10 cases (50%), with a mean period of 44.7±62.19 months. Recurrence occurred in three of informed cases. CONCLUSIONS: Synchronous manifestation of COF is rare. Female patients around the 3rd decade of life are more commonly affected. Bilateral involvement of the mandible and maxilla is the most common clinical presentation.

Leukoplakia and erythroplakia in youngers versus older individuals: a clinicopathological retrospective study.

BACKGROUND: The incidence of oral cancer has exhibited a rise within the young population. Considering that oral potentially malignant disorders (OPMDs) can precede the development of oral cancer, it is imperative to conduct studies in this particular younger population. This study aimed to evaluate the frequency and conduct a comparative analysis of the clinical-demographic characteristics of OPMDs in two distinct age groups. MATERIAL AND METHODS: A retrospective analysis was conducted with patients diagnosed with leukoplakia, erythroplakia, and leukoerythroplakia between 1965 and 2020. The individuals were categorized into two groups: those aged up to 40 years (Group Younger) and those aged 41 years and above (Group Older). RESULTS: A total of 640 lesions were subjected to analysis. Among these, patients aged up to 40 years constituted 10.63% of the sample, however, this proportion decreased significantly to 6.9% between 2010 and 2020. A predominant male representation was observed in both groups, with white lesions being the most common in both as well. However, the frequency of red or mixed lesions was significantly higher (p=0.034) in the older group, along with a higher prevalence of dysplastic lesions (26.9% versus 11.8%, p=0.01). Moreover, the older group exhibited a relatively higher percentage of smokers/ex-smokers (78.6%), compared to the younger group (61.5%, p=0.085) and alcohol consumers/ex-consumers (54.9% versus 22.7%, p=0.028). Elderly individuals exhibited an unfavorable progression (p=0.028). However, a logistic regression analysis identified as significant variables associated with malignant transformation, the presence of epithelial dysplasia, and red lesions diagnosed as erythroplakia. CONCLUSIONS: A declining frequency of OPMDs in young adults was observed over the years, whereas in older adults, these disorders exhibited an unfavorable progression.

Use of tamoxifene-controlled ovarian hyperstimulation for fertility preservation before breast cancer treatment: A prospective cohort study with a 5-year follow-up.

PURPOSE: Fertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP. METHODS: This multicentric prospective study included patients aged 18-40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes. RESULTS: Ninety-five patients were included between 2014 and 2017, aged 31.5 ± 4 years on average. 37.9 % received NAC and 62.1 % received adjuvant chemotherapy. FP procedure was successful in 89.5 % of the cycles. The mean number of collected and vitrified oocytes was 12.8 ± 7.9 and 9.8 ± 6.2, respectively. The mean duration of COS was 10.4 ± 1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1; 4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy. CONCLUSION: Tamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield.

Estimating the burden of care for oral potentially malignant disorders and oral cancer in Brazilian dental practice.

BACKGROUND: Oral cancer (OC) and oral potentially malignant disorders (OPMD) pose significant challenges to public health in Brazil. This study aimed to estimate the prevalence of oral cancer (OC) and oral potentially malignant disorders (OPMD) among patients who would be treated by Brazilian dentists during their careers. MATERIAL AND METHODS: Data on the number of dentists in Brazil were extracted from the 2022 census data, while incidence rates for OC cases were sourced from the Brazilian National Cancer Institute (INCA). Population estimates for Brazil and data on dental check-up rates were obtained from relevant national sources. RESULTS: Our analysis indicates that a general dentist in Brazil can expect to encounter on average two to three OC patients and on average 675 patients with OPMDs over a 35-year career. Regional disparities were observed, with certain regions showing higher than the average number of encounters due to low density of dentists in some rural districts. CONCLUSIONS: Brazilian dentists are likely to confront a substantial number of OC and OPMD cases during their professional tenure, emphasizing the need for public health policies aimed at enhancing dental surgeons' education in oral cancer prevention and early detection.

[Simultaneous occurrence of facial neurinoma in internal auditory canal and middle ear paraganglioma in patient. Unusual combination and difficult surgical task]. / Odnovremennoe vozniknovenie nevrinomy litsevogo nerva vo vnutrennem slukhovom prokhode i paragangliomy srednego ukha u patsientki: neobychnoe sochetanie i neprostaya khirurgicheskaya zadacha.

CLINICAL CASE: The 59-year-old patient complained of hearing loss on the left, ear murmur for a long time, periodic pain and discomfort in the left ear, dizziness for 6 months. She was found to have concurrent vestibular schwannoma in the internal auditory canal and temporal bone paraganglioma. Both tumors were removed in one operation. The schwannoma was removed by translabirinth access due to preoperative deafness, while the glomus tumor was removed during this access. Postoperative biopsy showed the presence of two unrelated diseases: paraganglioma (ICD-0 code 8690/3) and schwannoma (ICD-0 code 9560/0).

[Pediatric sensorineural hearing loss related COVID-19. Clinical cases]. / Sensonevral'naya tugoukhost' v detskom vozraste, assotsiirovannaya s COVID-19. Klinicheskie nablyudeniya.

COVID-19 is an acute respiratory coronavirus infection in 2019 caused by the SARS-CoV-2 virus. Currently, the number of neurological complications in the acute or delayed period of coronavirus disease is increasing, including peripheral disorders of the auditory analyzer. OBJECTIVE: To present clinical cases of sensorineural hearing loss in children under 5 years of age after a novel coronavirus infection. MATERIAL AND METHODS: We report 3 cases of unilateral and 1 case of bilateral acquired deep sensorineural hearing loss, while the association with SARS-CoV-2 has been confirmed anamnetically and/or laboratory. RESULTS: The SARS-CoV-2 virus can have a depressing effect on the cochlea on its own or enhance the toxic effect of viruses during the recovery period after COVID-19. The true frequency of acute sensorineural hearing loss of infectious origin in childhood and, as its outcome, the formation of persistent hearing impairment has not been determined. CONCLUSION: Viruses are volatile, contagious, and clinically dangerous due to their complications. Vaccination is the most effective measure for the prevention of infectious diseases.

Head and neck myofibroma: A case series of 16 cases and literature review.

BACKGROUND: This study aimed to explore the clinical, histopathologic, and immunohistochemical characteristics of myofibromas (MFs) affecting the head and neck region. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded tissue blocks of patients diagnosed with MFs in the head and neck were retrieved from the archives of three oral and maxillofacial pathology laboratories. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed, and follow-up status were retrieved from the patient's medical records or pathology reports. RESULTS: Sixteen cases were included in the study. Females were slightly more affected than males. The first and second decades of life were more prevalent. The most common locations were the alveolar ridge and cheek. Although rare, some of the patients were presented with intraosseous lesions. Microscopically, tumors consisted of plump, spindle-shaped myofibroblasts arranged in whorls or fascicles with varying degrees of differentiation. Immunohistochemically, diffuse positivity for vimentin and α-SMA was observed, while Ki-67 mostly showed low immunoreactivity (<5%). Treatment primarily involved complete excision. CONCLUSIONS: MFs in the head and neck region are rare and predominantly affect female patients during the second decade of life. Despite their rarity, central MFs should be considered in the differential diagnosis of intraosseous lesions in infants.