Clinical Management of Trauma to Primary Teeth and Delay in Eruption of Permanent Successor Tooth

Dental trauma is considered a complication in oral health, which has attracted the attention of researchers, as its prevalence has increased in recent years. Dental trauma in primary dentition can lead to early tooth loss and impairment of permanent successor teeth, depending on the stage of development of the tooth germ. The aim of the present study was to describe a clinical case of a 4-year-old child who was referred to a pediatric dentist after dental trauma and early loss of deciduous teeth. During the anamnesis, it was observed that the upper deciduous teeth (#51 and #61) were affected by successive traumas, resulting in the early loss of the affected teeth. Nance arch device with a tube-bar system was selected to restore function and aesthetics to the child, while the eruption of the successor permanent teeth was monitored. During the follow-up period, a delay in the eruption of #21 tooth was observed, and ulectomy of the region was indicated to allow the tooth eruption and the proper alignment of the central incisors, which occurred after 5 months of the surgical procedure. Through this report it was possible to conclude that the early diagnosis and the long-term periodic control of traumatic dental lesions in the primary dentition are of fundamental importance to prevent and minimize the damages that can occur to the permanent dentition. Keywords: Tooth Avulsion. Tooth, Deciduous. Dentition, Permanent. ResumoO traumatismo dentário é considerado uma complicação à saúde bucal que vem chamando a atenção de pesquisadores, pois sua prevalência tem aumentado nos últimos anos. O trauma dentário na dentição decídua pode ocasionar a perda precoce dos dentes, e comprometimento dos dentes sucessores permanentes, dependendo do estágio de desenvolvimento do germe dentário. O objetivo do presente estudo foi descrever um caso clínico de uma criança de 4 anos de idade que foi encaminhada ao odontopediatra após traumatismo dentário e perda precoce de dente decíduo. Durante a anamnese, foi observado que os dentes decíduos incisivos superiores (#51 e #61) foram afetados por sucessivos traumas, resultando na perda precoce dos dentes afetados. O dispositivo arco de Nance com sistema do tipo tubo-barra foi selecionado para devolver função e estética à criança, enquanto a irrupção dos dentes permanentes sucessores foi acompanhada. Durante consulta de controle, um atraso na erupção do dente #21 foi observado e a ulectomia da região foi indicada para permitir a irrupção do dente e o alinhamento adequado dos incisivos centrais, que ocorreu após 5 meses do procedimento cirúrgico. Por meio do presente relato foi possível concluir que o diagnóstico precoce e o controle periódico a longo prazo das lesões dentárias traumáticas na dentição decídua são de fundamental importância para prevenir e minimizar os prejuízos que podem ocorrer à dentição permanente. Palavras-chave: Avulsão Dentária. Dente Decíduo. Dentição Permanente.

ALL Maintenance Treatment for Early Loss of B-Cell Aplasia after Tisagenlecleucel Therapy

Chimeric antigen receptor (CAR) T-cell therapy is a new, effective treatment for patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukaemia (ALL). Tisagenlecleucel achieved a complete remission (CR) rate and minimal residual disease (MRD) negativity of 81% at 3 months in the pivotal study; overall survival (OS) was 76% at 12 months (Maude et al, 2018). Real world data confirmed similar outcomes, with 1-year OS of 77% and event free survival (EFS) of 52% (Pasquini et al, 2020). Relapse can occur in the form of CD19 negative or CD19 positive ALL. The latter is associated with lack of persistence of the CAR T product. B-cell aplasia (BCA) is an indirect measure of CAR T presence. Early (<6 months from infusion) loss of BCA is associated with high relapse risk (Pillai et al, 2019); therefore, allogeneic stem cell transplantation (SCT) is often considered. However, SCT is associated with therapy-related morbidity and mortality and not all patients will find a suitable donor. Therefore, the optimal management of patients with loss of BCA is yet to be defined. In our centre, we administered maintenance therapy to a cohort of children with early loss of BCA. When compared to UK patients undergoing SCT for the same indication, we noted promising early outcomes. We report the findings here. We collected data on children with r/r ALL treated with tisagenlecleucel at Great Ormond Street Hospital (GOSH) from January 2018 to January 2021 who presented loss of BCA without evidence of disease (negative molecular or flow cytometry MRD) within 12 months from infusion. Loss of BCA was defined as peripheral B-cell count ≥0.10 x 10^9/L or bone marrow (BM) CD19+ events ≥0.1%. We compared outcomes of children who received maintenance as per UKALL 2011 protocol at GOSH to those who received SCT for the same indication from all UK paediatric centres. Fourteen patients from GOSH met the inclusion criteria. Four had loss of BCA after 6 months from CAR T infusion, none of them received additional therapy and they are all alive and in CR at a median of 535 days after CAR T infusion (Figure 1, A and B). Ten patients recovered B cells at <6 months: 3 proceeded to SCT, 6 started on maintenance therapy, 1 received other treatment. In 2 cases, maintenance was commenced after a second CAR T infusion. Two patients from the UK cohort met the inclusion criteria for the SCT group. Analysis was performed on 6 children who received maintenance and 5 who had SCT. Baseline characteristics of the 2 groups were similar (male/female ratio, median age at infusion, cytogenetics). Time from infusion to loss of BCA did not differ: the median was 80 days (range 28-168) in children who had maintenance vs 93 days (range 28-150) in those who had SCT. At a median follow up of 511 days (range 222-812), 3/6 children who received maintenance relapsed at median 210 days after infusion and proceeded to further treatment, no patient relapsed post SCT. One child died of disease in the maintenance group 237 days after infusion, 2 children died of transplant related mortality in the SCT group at 222 and 422 days post infusion. OS and EFS did not differ statistically between the 2 groups, as shown in Figure 1 (C and D). We observed that outcome for patients who presented loss of BCA within or at 2 months from infusion was poor regardless of the intervention (maintenance or SCT). Management of patients who experience early loss of BCA after CAR T is challenging and there are little data to support optimal treatment. In our experience, maintenance therapy compared favourably with SCT with similar rate of OS and EFS. Of note, 2/5 patients died of TRM in the SCT group highlighting the toxicity of this approach in such heavily pre-treated patients. On the other hand, maintenance is a well tolerated, low-cost treatment which can be easily delivered on an out-patient basis. Our preliminary data support investigation of this strategy in larger, prospectively-recruited cohorts of patients. Moreover, our preliminary data suggest that the time of loss of BCA is a crucial clinical parameter, as children who developed it within 2 months from infusion had the worst outcome, possibly reflecting prior therapy intensity and its impact on autologous T cells. Figure 1 Figure 1. Disclosures Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.; Autolus: Patents & Royalties. Ghorashian: UCLB: Patents & Royalties: CARPALL; Novartis: Honoraria.

Race/ethnicity in relation to incident primary open-angle glaucoma characterized by autonomously determined visual field loss patterns

Purpose: We used an autonomous algorithm to classify incident visual field (VF) loss patterns in primary open-angle glaucoma (POAG). Subsequently, we compared racial differences in the risk of these regional VF loss patterns. Design/Participants: Participants (n=209,036) from the Nurses Health Study (NHS) (follow-up: 1980-2018); NHS2 (1989-2019); and Health Professionals Follow-up Study (HPFS; 1986-2018), aged ≥40 years and free of glaucoma. Methods: Demographics, medical and lifestyle information was assessed on biennial questionnaires. Incident POAG cases (n=1946) with reproducible Humphrey VF loss were confirmed with medical records. The total deviation information of the earliest reliable VF for each eye with POAG (n=2564) was extracted, and a statistical learning method was used to identified optimal solutions for regional vision loss patterns. Each POAG eye was assigned the VF pattern (archetype) based on the highest weighting coefficient. Multivariable-adjusted hazard ratios (HRs) for POAG of various archetypes and 95% confidence intervals (CIs) were estimated using per-eye Cox proportional hazards models. Covariates included cohort, age, glaucoma family history, socioeconomic status, lifestyle parameters, number of eye exams during follow-up, and medical conditions. False discovery rate (FDR) was used for multiple comparisons. Main outcome measures: POAG based on VF patterns. Results: Mean age was 58 years; 1.3% were Black, 1.2% were Asian, 1.1% were Hispanic-White and 96.4% were non-Hispanic White. We identified 14 archetypes: 1 representing no VF loss, 9 of early loss and 4 of advanced loss patterns. Compared to non-Hispanic Whites, Blacks were at significantly higher risk of POAG with early VF loss archetypes collectively (Blacks: HR=1.96, 95% CI=1.46, 2.63) and at even higher risk for POAG with advanced loss archetypes collectively (Blacks: HR=6.07, 95% CI=3.61, 10.21; p=0.0002 for the two estimates being different); no differences were observed for Asians or Hispanic Whites. For individual VF archetypes, Hispanic-Whites had FDR-significant higher risks of POAG of archetypes showing early paracentral defects and advanced superior loss while Blacks had FDR-significant higher risks of all advanced loss archetypes and 3 early loss patterns, including early paracentral defects. Conclusion: Among health professionals, compared to non-Hispanic-Whites, Blacks and Hispanic-Whites had higher risks of incident POAG with central and advanced VF loss.

Modified Intra-alveolar appliance — Case report

Arch space/ Tooth size discrepancy occurs whenever there is a early loss of the deciduous molars which eventually leads to malocclusion. Prevention of this discrepancy has always been a challenge for a pediatric dentist. This case report describes modified bilateral distal shoe appliance fabricated due to inadequate abutment support.

Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis

Objectives In alcoholic hepatitis (AH), dysfunctional T lymphocytes may contribute to the high mortality from infections. T lymphocyte activation is governed by the expression of co-stimulatory receptors such as 4-1BB balanced by inhibitory receptors such as Programmed Death receptor 1 (PD-1). 4-1BB expression is unaccounted for in AH, while PD-1 is elevated. We characterized expression of 4-1BB and PD-1 and the associated T lymphocyte functional status in AH and investigated whether these were associated with short-term mortality. Methods Thirty-five patients with AH (at diagnosis and days 7 and 90) were compared with healthy controls (HC). Spontaneous and in vitro stimulated receptor expression were quantified by flow cytometry, and plasma proteins by ELISA. Results At diagnosis, the patients showed increased stimulated 4-1BB responses of CD4+ T lymphocytes. Also, the frequencies of PD-1+ T lymphocytes both with and without co-expressed 4-1BB were increased. Further, interferon-gamma was predominantly produced in T lymphocytes co-expressing 4-1BB. A decrease in the frequency of spontaneous 4-1BB+ T lymphocytes and an increase in soluble 4-1BB during the first week after diagnosis were associated with higher mortality at day 90 in AH. PD-1 expression showed no systematic dynamics related to mortality. Conclusions We found an increased stimulated 4-1BB response of T lymphocytes in AH and early loss of these lymphocytes was associated with a higher short-term mortality. This suggests a role of T lymphocyte 4-1BB expression in the progression of AH.

Word-Initial Prevocalic [H-] in Middle English

The present contribution discusses the phonological reality of initial fricative h- in words of Germanic and French origin in dialectally identified 106 texts from the Innsbruck Corpus of Middle English Prose (Markus 2008), with the focus on native words where initial h- is frequently mute, as confirmed by (a) h-less spellings like ouse for house or especially (b) the use of the article an before h-nouns. In the early texts a phrase like an house may testify to the survival of the historical determiner (OE ān) put before both initial vowels and consonants, but in later texts this position may indicate mute initial h- in the following noun (or in an adjective before a noun). The paper offers numerical data concerning such distributions in particular Corpus texts as well as analogous data referring to the adjectives MIN and THIN (later on my and thy), where the final nasal consonant was lost when used in the function of an attribute. Consequently, this development led to the rise of a set of possessive adjectives with a syntactic, not phonological, distribution The data from the Innsbruck Corpus seem to indicate that an early loss of initial prevocalic h- in Middle English words of Germanic origin took place in particular texts rather than in texts from the whole region. The evidence from the Corpus shows that the implementation of the contemporary distribution, i.e., a before consonants and an before vowels, had a partly regional character, its first traces coming from as early as the 13th century.