Faculty Bibliography

Localized treatment of oligometastatic liver disease can improve both local control and survival. The liver is a frequent site of metastases from colorectal, breast, and lung cancers, but most patients are not eligible for surgical resection due to lesion number, location, or comorbidities. For these patients, non-surgical ablative methods such as radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) and increasingly microwave ablation (MWA) are used. RFA was used as the primary comparator in this review because it represents the most historically established and widely reported ablative modality in the comparative radiotherapy literature. While RFA has been the traditional approach, SBRT is emerging as a promising alternative, offering precise, non-invasive treatment. SBRT may be especially useful for larger lesions or tumors in locations where RFA is difficult to perform. However, high-quality evidence and large-scale trials are still needed to confirm its efficacy and define its role. This review compares the strengths and limitations of both methods and provides practical guidance for clinical decision-making in the treatment of patients with inoperable liver metastases.

BACKGROUND:The clinical and economic impact of breast cancer screening varies based on the modality, frequency, and age of the screened population. OBJECTIVE:To characterize changes in use and cost of breast cancer screening for older women. DESIGN/METHODS:Serial cross-sectional study using data from SEER-Medicare, 2009-2019. PARTICIPANTS/METHODS:Women 67 and older enrolled in Medicare fee-for-service. MAIN MEASURES/METHODS:Screening use and cost by age, frequency, and modality. We further categorized screening as cost-effective or cost-ineffective based on published economic analyses rather than guidelines. Cost-effective screening included biennial mammography among women < age 80, while cost-ineffective screening included annual mammography, addition of digital breast tomosynthesis (DBT), screening ultrasound, and any screening among women 80 and older. We estimated total annual spending on screening in Medicare fee-for-service, inflated to 2019 dollars. KEY RESULTS/RESULTS:Our sample included a mean of 229,683 (range 222,400- 244,793) Medicare beneficiaries annually. Biennial screening was stable among women 65-79, at 11.2% (95% CI 11.0-11.4) in 2009 and 11.9% (95% CI 11.7-12.0) in 2019. Annual screening was also stable at 32.5% (95% CI 32.3-32.7) in 2009 and 30.0% (95% CI 29.8-30.2) in 2019. Among women 80 and older, screening (annual or biennial) declined from 19% (95% CI 18.8-19.3) to 12.9% (95% CI 12.7-13.2). Between 2009-2019, use of DBT rose from 0% to 70.3% of screened women. Total spending on cost-effective screening rose from $569 million per year to $735 million per year, a 29% increase. Spending on cost-ineffective screening rose from $548 million to $1.025 billion, an 87% increase. By 2019, spending on cost-ineffective screening accounted for 58% of total spending. CONCLUSIONS:Screening costs for older women have risen, driven by expenditures on technologies that may not be cost-effective. Reducing use of low value screening could result in savings that could be reallocated toward high value screening and follow up testing.

Although mandibular implant-supported overdentures demonstrate high survival rates, uncertainty remains regarding their long-term biologic stability and maintenance burden, particularly across different attachment systems. Sixty edentulous patients were fitted with two-implant mandibular overdentures either by locator-type or ball retainers and followed up to a 5 years. At last follow-up, the survival rate of implants was 98.3% and 93.3% in terms of prostheses success; mean change of marginal bone was low. Maintenance requirements were frequent and mostly minor including insert/ matrix replacement and relines. Hence, long-term success is to be measured not just by survival.

CONTEXT/UNASSIGNED:A subset of metabolic diseases is caused by rare monogenic variants. Next-generation sequencing offers a promising approach for identifying such variants, but its application in clinical diagnostics for metabolic disease is limited and the diagnostic yield is unknown. OBJECTIVE/UNASSIGNED:To determine the diagnostic yield of clinical genome sequencing (GS) in adults presenting with common metabolic diseases. METHODS/UNASSIGNED:We performed clinical GS on 560 adults seen in New York clinical practices between August 2020 and December 2023. Participants presented with hyperlipidemia/hypertriglyceridemia (HLD/HTG), pre-diabetes, Type 2 diabetes mellitus (T2DM), and/or metabolic dysfunction-associated fatty liver disease/steatohepatitis (MAFLD/MASH). Variants in a curated set of 90 genes associated with monogenic forms of these conditions were classified as Pathogenic (P), Likely Pathogenic (LP), or Variant of Uncertain Significance (VUS) using ACMG/ClinGen guidelines. P/LP variants in ACMG secondary findings (v3.1) genes were also reported with participant consent. RESULTS/UNASSIGNED:The cohort had a female-to-male ratio of 1.7, with 18.6% African American and 22.6% Latino participants. The most common enrollment diagnoses were HLD/HTG (25%), T2DM (9%), pre-diabetes (7%), and MAFLD/MASH (4%). Many participants had multiple conditions (42% with two, 12% with three). Approximately one-third had reportable variants, with 6% classified as P/LP. The most common P/LP variants were in APOB and LDLR. CONCLUSION/UNASSIGNED:The prevalence of clinically significant (P/LP) variants related to primary metabolic disease in this cohort was 6%. An additional 5.5% of participants had P/LP variants in ACMG secondary findings genes. Future studies should refine participant selection for genome sequencing to optimize its diagnostic and clinical value.

PURPOSE/OBJECTIVE:Evidence-based dentistry has progressed from case reports and series to best evidence consensus statements; to non-randomized and randomized controlled studies; to systematic reviews (SRs), which analyze individual studies; and to umbrella reviews (URs), which now evaluate SRs. The purpose of this article is to review and summarize the findings of recent dental URs selected by the authors because they analyzed the quality of SRs, identified their strengths and weaknesses, and represented multiple disciplines of dentistry and diverse journals. MATERIALS AND METHODS/METHODS:A PubMed search was completed using the keywords "umbrella review, dentistry" and the filters "meta-analysis" and "systematic review" along with the years 2022-2024. There were 93 URs listed, with 56 being dental-related. The 56 URs were reviewed, and 15 were collectively selected by the authors to be summarized as examples of multiple dental disciplines and dental-related treatments published in a diverse group of dental journals. RESULTS:The 15 selected URs exhibited similar formats with findings based on the included SRs. The results of the 15 URs are summarized and presented along with the strengths and weaknesses noted in the SRs. CONCLUSIONS:The URs included in this article assessed the quality of SRs based on AMSTAR 2 (AMSTAR 2 is a critical appraisal tool used to assess the methodological quality of systematic reviews, particularly those focusing on healthcare interventions), ROBIS (ROBIS is the first rigorously developed tool designed specifically to assess the risk of bias in systematic reviews), and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Deficiencies were reported relative to the following items: failure to register the protocol before starting the review; incomplete literature search; absence of a list of excluded studies and lack of justification for the exclusions; inadequate review methods; lack of reporting the sources of funding; failing to assess risk of bias (ROB) or an unsatisfactory technique to assess ROB; not listing potential sources of conflict of interest; and lack of homogeneity in the study design, which prevented performing a meta-analysis. These findings indicate the need for careful study of SR and UR guidelines related to design and review, assessment of bias risk, and review reporting before applying the conclusion to clinical practice. Clinicians need to be aware of the deficiencies present in SRs and URs. Also, it is important to recognize that reviews are based on only those studies that met the inclusion criteria of the authors, and the exclusion of studies is fraught with potential bias.

RATIONALE/BACKGROUND:Aggression is an innate social behavior prevalent across animal species. However, in modern human society, inter-personal aggression is considered disruptive and detrimental to both families and communities. Clinically, antipsychotics, which primarily target dopamine (DA) receptors, have been widely used to suppress hyper-aggression. However, the mechanisms underlying the effect of the antipsychotics remain incompletely understood. OBJECTIVES/OBJECTIVE:We reviewed key steps in brain DA synthesis and summarized genetic and pharmacological evidence supporting the role of the mesolimbic DA system in aggression. Next, we discussed recent circuit studies that elucidate the DA action in modulating aggression-related brain regions. These lines of evidence collectively suggest that DA acts on different brain regions to facilitate aggression and self-learning, and signals the valence of the fighting experience.

Panic provocation tests have been widely used to investigate the biological underpinnings of panic disorder (PD). However, their diagnostic specificity remains uncertain, as several agents can also induce panic-like reactions in healthy individuals. This meta-analysis estimated and compared diagnostic odds ratios (DORs) across different provocation methods. Random-effects meta-analyses were conducted using the Hartung-Knapp adjustment. Based on 123 studies including 5693 participants, sodium lactate infusion showed the highest pooled DOR (24.77, 95% CI 19.03-32.25, GRADE certainty = High), followed by isoproterenol (18.85, 95% CI 12.39-28.66, GRADE certainty = Moderate), cholecystokinin tetrapeptide (CCK-4; 15.03, 95% CI 7.83-28.84, GRADE certainty = Moderate), meta-chlorophenyl piperazine (m-CPP; 14.51, 95% CI 4.67-45.07, GRADE certainty = Low), caffeine (14.11, 95% CI 4.79-41.54, GRADE certainty = Moderate), hyperventilation (11.89, 95% CI 6.51-21.73, GRADE certainty = High), carbon dioxide inhalation (CO₂; 11.12, 95% CI 8.63-14.32, GRADE certainty = High), and yohimbine (7.87, 95% CI 1.12-55.13, GRADE certainty = Very low). Breath holding, fenfluramine and flumazenil did not demonstrate statistically significant discriminative ability. Meta-regression analysis confirmed that sodium lactate yielded significantly higher DORs than m-CPP, hyperventilation, CO₂, fenfluramine, flumazenil, and yohimbine. No substantial between-study heterogeneity or publication bias was identified across the pooled analyses. These findings suggest that provocation methods targeting acid-base balance, especially sodium lactate infusion, are associated with superior diagnostic discrimination between individuals with PD and healthy controls.

As the population ages, the incidence and prevalence of musculoskeletal degeneration, such as osteoarthritis, increase. While the currently accepted treatment options provide symptomatic and functional improvement, they do not halt the progression of osteoarthritis. This results in the eventual need for surgery for many patients with advanced osteoarthritis. Due to the seemingly inevitable progression of OA, many clinicians and researchers have shifted their focus to regenerative therapies. Orthobiologics, a specific type of regenerative therapy designed to treat orthopedic conditions, has been gaining traction in recent years due to the utilization of autologous biological substances and synthetic peptides in healing musculoskeletal injuries and degenerative conditions. Orthobiologics can be distinguished into one of four classes: cell-based, biologic fluids-based, matrix-based, molecular-based, and based on their composition. In this review, key examples of each class, mechanism of action, and current clinical data for each agent are examined. Limitations of current orthobiologics involve a lack of standardization in the preparation and administration of each agent, as well as uniformity in assessment endpoints across different clinical studies. Lastly, we will discuss future directions of orthobiologics as a therapy for the treatment of osteoarthritis.