Therapeutic mammoplasty: a "wise" oncoplastic choice-lessons from the largest single-center cohort from Asia.

Introduction: The majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM. Methods: All patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures. Results: The median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1-pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains. Conclusion: We conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation.

Evidence-based fact checking for selective procedures in restorative dentistry.

OBJECTIVES: Similar to other dental specialties, there are many clinical procedures in restorative dentistry that may or may not be supported by good evidence. Thus, the effectiveness of these procedures is uncertain. The aim of this paper is to reduce this knowledge gap by critically inspecting selective procedures in restorative dentistry and exploring if these well-established or widely advocated treatment modalities are necessary for improving treatment outcomes based on the best available evidence. MATERIALS AND METHODS: A MEDLINE search was conducted to identify research on selective procedures while focusing on clinical trials and systematic reviews. Due to their practical relevance in the decision-making process, cost-effectiveness analyses were also included. RESULTS: Mixed results were identified regarding the included interventions. Some procedures had adequate evidence supporting them while others were mostly based on beliefs. CONCLUSIONS: A critical review of the available literature indicates that some common restorative procedures lack adequate support from high-quality research evidence. CLINICAL RELEVANCE: This paper attempts to highlight the need to critically examine the scientific validity of traditional knowledge and techniques through the context of current research evidence. This will not only help generate consensus between educators, clinicians, and researchers regarding restorative procedures but will also lead to improved patient care and outcomes.

Burden of COVID-19 and case fatality rate in Pune, India: an analysis of the first and second wave of the pandemic.

Objective: To assess trends in case incidence and fatality rate between the first and second waves, we analyzed programmatic COVID-19 data from Pune city, an epicenter of COVID-19 cases in India. Method: The trends of cases incidence, time-to-death and case fatality rate (CFR) were analyzed. Poisson regression models adjusted for age and gender were used to determine the independent effect of pandemic waves on mortality. Results: Of 465 192 COVID-19 cases, 162 182 (35%) were reported in the first wave and 4146 (2.5%) deaths, and 275 493 (59%) in the second wave and 3184 (1.1%) deaths (P<0.01). The overall CFR was 1.16 per 1000 person-days (PD), which declined from 1.80 per 1000 PD during the first wave to 0.77 per 1000 PD in the second. The risk of death was 1.49 times higher during the first wave (adjusted CFR ratio (aCFRR)1.49; 95% CI: 1.37-1.62) and 35% lower in the second wave (aCFRR 0.65; 95% CI: 0.59-0.70). Conclusion: The burden of COVID-19 cases and deaths was more significant in the second wave; however, the CFR declined as the pandemic progressed. Nevertheless, investigating new therapies and implementing mass vaccination against COVID-19 are urgently needed.

A critical analysis of research methods and experimental models to study the load capacity and clinical behaviour of the root filled teeth.

The prognosis of root-filled teeth depends not only on a successful root canal treatment but also on the restorative prognosis. This critical review discusses the advantages and limitations of various methodologies used to assess the load capacity or clinical survivability of root-filled teeth and restorations. These methods include static loading, cyclic loading, finite element analysis and randomized clinical trials. In vitro research is valuable for preclinical screening of new dental materials or restorative modalities. It also can assist investigators or industry to decide whether further clinical trials are justified. It is important that these models present high precision and accuracy, be reproducible, and present adequate outcomes. Although in vitro models can reduce confounding by controlling important variables, the lack of clinical validation (accuracy) is a downside that has not been properly addressed. Most importantly, many in vitro studies did not explore the mechanisms of failure and their results are limited to rank different materials or treatment modalities according to the maximum load capacity. An extensive number of randomized clinical trials have also been published in the last years. These trials have provided valuable insight on the survivability of the root-filled tooth answering numerous clinical questions. However, trials can also be affected by the selected outcome and by intrinsic and extrinsic biases. For example, selection bias, loss to follow-up and confounding. In the clinical scenario, hypothesis-based studies are preferred over observational and retrospective studies. It is recommended that hypothesis-based studies minimize error and bias during the design phase.

Genome-Wide Screen for Context-Dependent Tumor Suppressors Identified Using in Vivo Models for Neoplasia in Drosophila.

Genetic approaches in Drosophila have successfully identified many genes involved in regulation of growth control as well as genetic interactions relevant to the initiation and progression of cancer in vivo Here, we report on large-scale RNAi-based screens to identify potential tumor suppressor genes that interact with known cancer-drivers: the Epidermal Growth Factor Receptor and the Hippo pathway transcriptional cofactor Yorkie. These screens were designed to identify genes whose depletion drove tissue expressing EGFR or Yki from a state of benign overgrowth into neoplastic transformation in vivo We also report on an independent screen aimed to identify genes whose depletion suppressed formation of neoplastic tumors in an existing EGFR-dependent neoplasia model. Many of the positives identified here are known to be functional in growth control pathways. We also find a number of novel connections to Yki and EGFR driven tissue growth, mostly unique to one of the two. Thus, resources provided here would be useful to all researchers who study negative regulators of growth during development and cancer in the context of activated EGFR and/or Yki and positive regulators of growth in the context of activated EGFR. Resources reported here are available freely for anyone to use.

Promoter Proximal Pausing Limits Tumorous Growth Induced by the Yki Transcription Factor in Drosophila.

Promoter proximal pausing (PPP) of RNA polymerase II has emerged as a crucial rate-limiting step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT), and the negative elongation factor (NELF), which are highly conserved from Drosophila to humans. Here, we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhances Yki-driven growth, leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression cooperates with Yki in driving neoplastic growth. Interestingly, overexpression of CDK9 on its own or in the background of depletion of one of the components of 7SK snRNP or the NELF complex necessarily, and specifically, needed Yki overexpression to cause tumorous growth. Genome-wide gene expression analyses suggested that deregulation of protein homeostasis is associated with tumorous growth of wing imaginal discs. As both Fat/Hippo/Yki pathway and PPP are highly conserved, our observations may provide insights into mechanisms of oncogenic function of YAP-the ortholog of Yki in humans.

Universal dental adhesives: Current status, laboratory testing, and clinical performance.

Increasing demand for simplified and user-friendly adhesive systems has led to the development of a new class of adhesives termed as Universal Adhesives (UAs). The term "Universal" reflects manufacturers' claims that these adhesives can be applied with any adhesion strategy and offer the versatility of use with a variety of direct and indirect restorative materials. The aim of this review was to synthesize the literature regarding the current status of UAs, their adhesion potential to various substrates and their performance in different restorative situations. In vitro studies, clinical trials and systematic reviews were identified utilizing controlled vocabulary and keyword searches in Medline and EMBASE databases. About 282 studies (272 in vitro studies; 11 clinical studies) were included. Available laboratory and clinical evidence does not support the claim that UAs can be used with any adhesive strategy. Although, they can chemically bond to various tooth and direct/indirect restorative substrates, the stability of this bond is material-dependent and subject to hydrolytic degradation. Hence, additional measures are still needed to ensure long-term durability. which undermines the versatility of UAs. The lack of long-term data regarding the clinical performance of UAs further complicates clinical decision-making. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2121-2131, 2019.

Digital versus conventional impressions for full-coverage restorations: A systematic review and meta-analysis.

BACKGROUND: The primary objective of this systematic review was to investigate the survival of full-coverage restorations fabricated by using digital impressions (DIs) versus that of those fabricated by using conventional impressions. The authors also compared secondary outcomes of marginal and internal fit and occlusal and interproximal contacts. TYPES OF STUDIES REVIEWED: The authors conducted a systematic literature search in multiple databases to identify clinical trials with no restrictions by publication type, date, or language. The authors assessed study-level risk of bias and outcome-level strength of evidence. The authors performed a meta-analysis by using a random-effects model. RESULTS: Ten studies met the inclusion criteria. The authors identified no studies in which the investigators compared the impression techniques with respect to survival of full-coverage restorations. Mean differences for marginal gap and internal gap were -9.0 micrometers (95% confidence interval, -18.9 to 0.9) and -15.6 µm (95% confidence interval, -42.6 to 11.4), respectively. Studies assessing internal gap were substantially heterogeneous (I2 = 72%; P = .003). CONCLUSIONS AND PRACTICAL IMPLICATIONS: Research is lacking to draw robust conclusions about the relative benefits of DIs in terms of restoration survival. Low-quality evidence for marginal fit and internal fit suggested similar performance for both techniques. Evidence quality for interproximal contact and occlusal contact was very low and insufficient to draw any conclusions regarding how the impression techniques compared. Given the uncertainty of the evidence, results should be interpreted with caution. With increasing popularity and adoption of digital scanners by dentists, pragmatic practice-based trials involving standardized, patient-centered outcomes may improve confidence in the comparative effectiveness of DIs.

Influence of 2 caries-detecting devices on clinical decision making and lesion depth for suspicious occlusal lesions: A randomized trial from The National Dental Practice-Based Research Network.

BACKGROUND: A suspicious occlusal carious lesion (SOCL) can be defined as a lesion with no cavitation and no radiographic radiolucency but for which caries is suspected. The authors evaluated whether using a device changed the percentage of SOCLs that were opened surgically and, among those SOCLs that were opened, the proportion that had penetrated into dentin. METHODS: Eighty-two dentists participated. In phase 1 of the study, dentists identified approximately 20 SOCLs, obtained patient consent, and recorded information about the lesion, treatment or treatments, and depth, if opened. Dentists were then randomly assigned into 1 of 3 groups: no device, DIAGNOdent (KaVo), and Spectra (Air Techniques). In phase 2, dentists enrolled approximately 20 additional patients and recorded the same phase 1 information while using the assigned device to help make their treatment decisions. A mixed-model logistic regression was used to determine any differences after randomization in the proportion of lesions opened and, if opened, the proportion of lesions that penetrated into dentin. RESULTS: A total of 1,500 SOCLs were enrolled in each phase. No statistically significant difference was found in the change in proportion of lesions receiving invasive treatment from phase 1 to phase 2 across the 3 groups (P = .33) or in the change in proportion of percentage of opened lesions that extended into dentin (P = .31). CONCLUSION: Caries-detecting devices in the study did not change substantially dentists' decisions to intervene or the accuracy of the intervention decision in predicting lesion penetration into dentin. PRACTICAL IMPLICATIONS: The caries-detecting devices tested may not improve dentists' clinical decision making for SOCLs.

Early childhood caries-related visits to emergency departments and ambulatory surgery facilities and associated charges in New York state.

BACKGROUND: The authors assessed the extent of early childhood caries- (ECC-) related visits to emergency departments (EDs) and ambulatory surgery facilities (ASFs) in children younger than 6 years and associated treatment charges in New York state from 2004 through 2008. METHODS: The authors obtained data from the New York state's Statewide Planning and Research Cooperative System (Albany) and calculated descriptive statistics and rates according to selected indicators, as well as total and average per-visit treatment charges. RESULTS: From 2004 through 2008, the number of ECC-related visits to EDs and ASFs increased by 349 and 1,039, respectively. Most ECC-related visits were to ASFs. The total annual treatment charges increased from $18.5 million to $31.3 million from 2004 to 2008, and average per-visit charges increased from $4,237 to $5,501 during the same period. CONCLUSIONS: ECC-related visits to EDs and ASFs by children younger than 6 years and the associated treatment charges increased substantially from 2004 through 2008 in New York state. Practice Implications. Dental professionals need to determine the reasons parents seek dental care for their children in EDs and ASFs and effective strategies for preventing ECC to avoid the subsequent need for seeking dental care in EDs and ASFs.