Food, nutrition, and autism: from soil to fork.

Food and nutrition-related factors have the potential to impact development of autism spectrum disorder (ASD) and quality of life for people with ASD, but gaps in evidence exist. On 10 November 2022, Tufts University's Friedman School of Nutrition Science and Policy and Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships of food and nutrition with ASD. This meeting report summarizes the presentations and deliberations from the meeting. Topics addressed included prenatal and child dietary intake, the microbiome, obesity, food-related environmental exposures, mechanisms and biological processes linking these factors and ASD, food-related social factors, and data sources for future research. Presentations highlighted evidence for protective associations with prenatal folic acid supplementation and ASD development, increases in risk of ASD with maternal gestational obesity, and the potential for exposure to environmental contaminants in foods and food packaging to influence ASD development. The importance of the maternal and child microbiome in ASD development or ASD-related behaviors in the child was reviewed, as was the role of discrimination in leading to disparities in environmental exposures and psychosocial factors that may influence ASD. The role of child diet and high prevalence of food selectivity in children with ASD and its association with adverse outcomes were also discussed. Priority evidence gaps identified by participants include further clarifying ASD development, including biomarkers and key mechanisms; interactions among psychosocial, social, and biological determinants; interventions addressing diet, supplementation, and the microbiome to prevent and improve quality of life for people with ASD; and mechanisms of action of diet-related factors associated with ASD. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and ASD.

Revisiting the Definition of 'Healthy' Participants in Substantiation of Structure/Function Claims for Dietary Supplements.

Concepts and definitions of 'healthy' have been evolving within clinical treatment algorithms as well as reference standards such as Body Mass Index and Dietary Reference Intakes. Consumers' perception of the word 'healthy' is also changing to reflect longer life span, need to stay active and in a good state of mental well-being while managing multiple diseases. Guidelines from the US Food and Drug Administration indicate that substantiating evidence for support of Structure/Function (S/F) claims for dietary supplements is best derived from clinical research conducted in a 'healthy' population. S/F claims cannot be represented to diagnose, treat, cure or prevent any disease. However, in this context, the term 'healthy' is non-descriptive and largely interpreted as an absence of disease. Guidelines for treatment of disease have been broadened to include biomarkers of disease risk such that the pool of 'healthy' volunteers eligible to be enrolled in clinical trials for S/F claim substantiation is greatly diminished. This perspective presents the challenges faced by the food and dietary supplement industry and by researcher efforts designed to substantiate S/F claims and suggest the phrase 'physiologically stable' or 'apparently healthy' as descriptions better suited to replace the term 'healthy.'

Technical Nuances of Anterior Column Construction for the Treatment of Osteomyelitis-Induced Cervical Kyphoscoliotic Deformity: An Operative Video Illustration.

Pyogenic vertebral osteomyelitis is a bacterial infection of the vertebral body often caused by hematogenous spread from a distant site with 3%-11% of cases affecting the cervical spine.1,2 Patients at risk for osteomyelitis are intravenous drug users, patients with diabetes, patients in dialysis, and males older than 50 years of age. In severe cases where infection causes osseous destruction of the vertebral column lending to a loss of normal sagittal and coronal plane alignment, neurologic impairment, or spinal instability, surgical correction may be required.3 A 38-year-old woman with a medical history of intravenous drug use presented with a 1-week history of progressive paresthesias, subjective loss of lower extremity sensation, and severe right upper extremity weakness. Neurologic examination was notable for significant weakness in the right deltoids, biceps, and triceps. Magnetic resonance imaging cervical spine revealed significant kyphosis at C4-C5 secondary to destruction of the C4 and C5 vertebral bodies and anterior and posterior epidural fluid collection at C2-C3 and C7-T1, respectively. Surgery was proposed through a combined anteroposterior approach with head and neck surgeons. Anteriorly, she underwent a C2-C3 and C6-C7 ACDF and C4, C5 corpectomies (Video 1). The patient was then transitioned to the prone position and underwent C3-T3 posterior fusion with instrumentation and C3-C7 laminectomies. Correction of sagittal imbalance should restore normal physiologic spinal alignment while promoting a successful fusion.4 The patient was discharged to acute rehabilitation after an uneventful postoperative course. At 5-month follow-up, she has regained antigravity strength in right upper extremity and reports significant reduction in neck pain.

Effect of distance of treatment center on survival for HPV-negative head and neck cancer patients.

BACKGROUND: In rural states, travel burden for complex cancer care required for head and neck squamous cell carcinoma (HNSCC) may affect patient survival, but its impact is unknown. METHODS: Patients with HPV-negative HNSCC were retrospectively identified from a statewide, population-based study. Euclidian distance from the home address to the treatment center was calculated for radiation therapy, surgery, and chemotherapy. Multivariable Cox proportional hazards models were used to examine the risk of 5-year mortality with increasing travel quartiles. RESULTS: There were 936 patients with HPV-negative HNSCC with a mean age of 60. Patients traveled a median distance of 10.2, 11.1, and 10.9 miles to receive radiation therapy, surgery, and chemotherapy, respectively. Patients in the fourth distance quartile were more likely to live in a rural location (p < 0.001) and receive treatment at an academic hospital (p < 0.001). Adjusted overall survival (OS) improved proportionally to distance traveled, with improved OS remaining significant for patients who traveled the furthest for care (third and fourth quartile by distance). Relative to patients in the first quartile, patients in the fourth had a reduced risk of mortality with radiation (HR 0.59, 95% CI 0.42-0.83; p = 0.002), surgery (HR 0.47, 95% CI 0.30-0.75; p = 0.001), and chemotherapy (HR 0.56, 95% CI 0.35-0.91; p = 0.020). CONCLUSION: For patients in this population-based cohort, those traveling greater distances for treatment of HPV-negative HNSCC had improved OS. This analysis suggests that the benefits of coordinated, multidisciplinary care may outweigh the barriers of travel burden for these patients.

A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo-immunotherapy in the curative setting is not established. METHODS: This phase 2, single-arm, multicenter study evaluated neoadjuvant chemo-immunotherapy with carboplatin, nab-paclitaxel, and durvalumab in patients with resectable locally advanced HNSCC. The primary end point was a hypothesized pathologic complete response rate of 50%. After chemo-immunotherapy and surgical resection, patients received study-defined, pathologic risk adapted adjuvant therapy consisting of either durvalumab alone (low risk), involved field radiation plus weekly cisplatin and durvalumab (intermediate risk), or standard chemoradiation plus durvalumab (high risk). RESULTS: Between December 2017 and November 2021, 39 subjects were enrolled at three centers. Oral cavity was the most common primary site (69%). A total of 35 of 39 subjects underwent planned surgical resection; one subject had a delay in surgery due to treatment-related toxicity. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. Post treatment imaging demonstrated an objective response rate of 57%. Pathologic complete response and major pathologic response were achieved in 29% and 49% of subjects who underwent planned surgery, respectively. The 1-year progression-free survival was 83.8% (95% confidence interval, 67.4%-92.4%). CONCLUSIONS: Neoadjuvant carboplatin, nab-paclitaxel, and durvalumab before surgical resection of HNSCC were safe and feasible. Although the primary end point was not met, encouraging rates of pathologic complete response and clinical to pathologic downstaging were observed.

Osseointegration and Bone Resorption of Scapula Tip Free Flaps in Mandibular Reconstruction.

OBJECTIVES: Bone resorption of more conventional vascularized bone grafts have been well described showing minimal resorption over time. Few studies have evaluated osseous union and bone resorption in scapula tip free flaps (STFF) in the reconstruction of mandibulectomy defects. We aimed to describe our series on STFF with respect to osseous union and bone resorption over time. METHODS: Retrospective chart review of patients receiving STFF from January 2014-January 2017 (n = 25). A neuroradiologist analyzed follow-up CT scans to assess (1) STFF complete, partial, or no osseous union with native mandible and (2) STFF volume change over time in a subset with multiple follow-up scans (n = 18). RESULTS: Twenty-three of 25 patients (92%) showed complete or partial STFF osseous union with native mandible either distally or proximally. STFF volume change ranged from +4.8 to -54% (median -0.5%) over median follow-up interval of 23 months. History of chemoradiation therapy, bisphophonate use, sex, age, or smoking history did not correlate with bone resorption. CONCLUSIONS: STFFs shows high rates of osseous union and limited bone resorption that is equivalent to, or less than, vascularized fibular and iliac crest flaps. Clinically, this translates into both optimal healing and functional and cosmetic outcomes, especially in the setting of prior therapies. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2597-2602, 2023.

Validation of Food Compass with a healthy diet, cardiometabolic health, and mortality among U.S. adults, 1999-2018.

The Food Compass is a nutrient profiling system (NPS) to characterize the healthfulness of diverse foods, beverages and meals. In a nationally representative cohort of 47,999 U.S. adults, we validated a person's individual Food Compass Score (i.FCS), ranging from 1 (least healthful) to 100 (most healthful) based on cumulative scores of items consumed, against: (a) the Healthy Eating Index (HEI) 2015; (b) clinical risk factors and health conditions; and (c) all-cause mortality. Nationally, the mean (SD) of i.FCS was 35.5 (10.9). i.FCS correlated highly with HEI-2015 (R = 0.81). After multivariable-adjustment, each one SD (10.9 point) higher i.FCS associated with more favorable BMI (-0.60 kg/m2 [-0.70,-0.51]), systolic blood pressure (-0.69 mmHg [-0.91,-0.48]), diastolic blood pressure (-0.49 mmHg [-0.66,-0.32]), LDL-C (-2.01 mg/dl [-2.63,-1.40]), HDL-C (1.65 mg/d [1.44,1.85]), HbA1c (-0.02% [-0.03,-0.01]), and fasting plasma glucose (-0.44 mg/dL [-0.74,-0.15]); lower prevalence of metabolic syndrome (OR = 0.85 [0.82,0.88]), CVD (0.92 [0.88,0.96]), cancer (0.95 [0.91,0.99]), and lung disease (0.92 [0.88,0.96]); and higher prevalence of optimal cardiometabolic health (1.24 [1.16,1.32]). i.FCS also associated with lower all-cause mortality (HR = 0.93 [0.89,0.96]). Findings were similar by age, sex, race/ethnicity, education, income, and BMI. These findings support validity of Food Compass as a tool to guide public health and private sector strategies to identify and encourage healthier eating.

Breaking new frontiers: Assessment and re-evaluation of clinical trial design for nutraceuticals.

Despite sophisticated study designs and measurement tools, we have yet to create an innovative space for diet and dietary supplements in the health care system. The path is challenging due to current hierarchies of scientific evidence and regulatory affairs. The role of the randomized, double-blind, placebo-controlled clinical trial (RCT) as a research approach functions well to characterize the benefits and risks of drugs but lacks the sensitivity to capture the efficacy and safety of nutraceuticals. While some facets of RCTs can be relevant and useful when applied to nutraceuticals, other aspects are limiting and potentially misleading when taken in their entirety. A differentiation between guidelines for evidence-based medicine and the evidence required for nutrition spotlight the need to reconceptualize constituents of the RCT and their applicability with relevance to health promotion. This perspective identifies the limitations of the traditional RCT to capture the complexities of nutraceuticals and proposes the N-of-1 as Level 1 evidence better suited for the proof of efficacy of nutraceuticals.

Treatment of Localized Amyloid Light Chain Amyloidosis With External Beam Radiation Therapy.

PURPOSE: Localized amyloidosis is a condition characterized by deposits of fibrillary proteins confined to a single organ. The most common subtype is amyloid light chain amyloidosis, which is caused by secretion of amyloidogenic light chain by a monoclonal population of plasma cells. We present a review and discussion of the literature in the context of a case presentation of localized amyloid light chain amyloidosis of the nasopharynx treated with radiation alone. METHODS AND MATERIALS: We reviewed literature relevant to this topic from 1970 to the present. Relevant studies, reports, and articles were summarized in table form. RESULTS: Surgical resection has historically been the primary therapeutic modality for these patients, with radiation being reserved for recurrent lesions or for those unfit for surgery. Although the data are limited to small retrospective series, radiation has been shown to provide good control with mild toxicity that is as good as or better than surgery. Doses range from 20 to 45 Gy, conventionally fractionated. There is no known risk of progression to systemic disease without local therapy. CONCLUSIONS: We recommend local therapy for symptomatic patients after systemic disease has been excluded. We generally recommend radiation in the setting of recurrent lesions, unacceptable toxicity with surgery, poor surgical candidates, and as the initial modality in select patients (elderly individuals with bothersome but nonobstructive lesions).

Precision nutrition: Maintaining scientific integrity while realizing market potential.

Precision Nutrition (PN) is an approach to developing comprehensive and dynamic nutritional recommendations based on individual variables, including genetics, microbiome, metabolic profile, health status, physical activity, dietary pattern, food environment as well as socioeconomic and psychosocial characteristics. PN can help answer the question "What should I eat to be healthy?", recognizing that what is healthful for one individual may not be the same for another, and understanding that health and responses to diet change over time. The growth of the PN market has been driven by increasing consumer interest in individualized products and services coupled with advances in technology, analytics, and omic sciences. However, important concerns are evident regarding the adequacy of scientific substantiation supporting claims for current products and services. An additional limitation to accessing PN is the current cost of diagnostic tests and wearable devices. Despite these challenges, PN holds great promise as a tool to improve healthspan and reduce healthcare costs. Accelerating advancement in PN will require: (a) investment in multidisciplinary collaborations to enable the development of user-friendly tools applying technological advances in omics, sensors, artificial intelligence, big data management, and analytics; (b) engagement of healthcare professionals and payers to support equitable and broader adoption of PN as medicine shifts toward preventive and personalized approaches; and (c) system-wide collaboration between stakeholders to advocate for continued support for evidence-based PN, develop a regulatory framework to maintain consumer trust and engagement, and allow PN to reach its full potential.

Reconstruction of oral cavity defects using myogenous-only scapular tip free-flaps.

Background: Oral cavity reconstruction is very challenging anatomical subsite to reconstruct. Large defects often require free tissue reconstruction to provide the best chance of form and function. Additionally, free tissue reconstruction aids to prevent fistula formation. We aimed to determine outcomes of oral cavity defect reconstruction using scapular tip free flaps with a myogenous intraoral component. Methods: All patients with a mandibular or maxillary bony defect that included a disruption of the intraoral mucosa component between 07/1/14 and 07/31/17. Patients were reconstructed with a scapular tip free flap, which included a muscular component that was used to recreate the oral mucosa. The primary study outcomes were flap success rates, development of orocutaneous or oronasal fistula, rate of resuming oral diet as well as the occurrence of medical and surgical complications in the first month following surgery. The tested hypothesis was formulated before data collection began. Results: Twenty-five patients were identified by the study criteria. There was one (4%) flap that failed, while orocutaneous fistula occurred in two patients (8%). Prior history of osteoradionecrosis was a statistically significant predictor of overall complication (p < .05). Conclusions: Intraoral myogenous reconstruction allows for re-mucosalization of the oral cavity defect and is associated with high viability and low-complication rates. In patients with amenable oral mucosal defects, a myogenous scapular tip free flap is a suitable reconstructive option.

Melanoma In Situ of the Hard Palate.

Mucosal melanoma of the oral cavity is rare and highly aggressive, thought to represent less than 1% of melanomas. Within this subgroup, melanoma in situ has been rarely described. We describe the case of a 54-year-old male with history of tobacco use presented with extensive pigmented changes to the hard and soft palate. Biopsy demonstrated melanoma in situ. Mucosal surgical resection was performed with all peripheral epithelial margins involved and negative deep margins. After extensive multidisciplinary discussion, remaining mucosal margins were re-resected to the teeth and posteriorly onto the soft palate. Deep margins remained negative with melanoma in situ still present peripherally. The patient is routinely surveilled without evidence of recurrence. Oral cavity melanoma in situ has been rarely described. The treatment of choice is surgical excision, ranging from wide local excision to composite resections, with consideration given to medical adjuncts. This unique entity should be considered in pigmented oral abnormalities.

Dietary Supplements for Weight Management: A Narrative Review of Safety and Metabolic Health Benefits.

Dietary supplements for weight management include myriad ingredients with thermogenic, lipotropic, satiety, and other metabolic effects. Recently, the safety of this product category has been questioned. In this review, we summarize the safety evidence as well as relevant clinical findings on weight management and metabolic effects of six representative dietary supplement ingredients: caffeine, green tea extract (GTE), green coffee bean extract (GCBE), choline, glucomannan, and capsaicinoids and capsinoids. Of these, caffeine, GTE (specifically epigallocatechin gallate [EGCG]), and choline have recommended intake limits, which appear not to be exceeded when used according to manufacturers' instructions. Serious adverse events from supplements with these ingredients are rare and typically involve unusually high intakes. As with any dietary component, the potential for gastrointestinal intolerance, as well as possible interactions with concomitant medications/supplements exist, and the health status of the consumer should be considered when consuming these components. Most of the ingredients reviewed also improved markers of metabolic health, such as glucose, lipids, and blood pressure, although the data are limited for some. In summary, weight management supplements containing caffeine, GTE, GCBE, choline, glucomannan, and capsaicinoids and capsinoids are generally safe when taken as directed and demonstrate metabolic health benefits for overweight and obese people.

The Effect of Multi-Vitamin/Multi-Mineral Supplementation on Nutritional Status in Older Adults Receiving Drug Therapies: A Double-Blind, Placebo-Controlled Trial.

Polypharmacy regimens may increase the susceptibility of older adults to micronutrient inadequacy and deficiency via impairment of nutritional status. We hypothesized that a multi-vitamin-mineral supplement (MVMS) could improve nutritional status in older adults prescribed diuretics, metformin, and/or proton pump inhibitors (PPIs). We conducted a randomized, double-blind, placebo controlled, parallel clinical trial in which eligible subjects were instructed to consume either a MVMS or placebo for 16 wk. Fasting blood was collected at baseline, 8, and 16 wk and the status of selected vitamins and minerals determined. Thirty-five and 19 men and women aged 45-75 yrs in the in MVMS and placebo arms, respectively, completed the trial. The mean total number of medications among the three drug classes taken by participants did not differ between two groups. The status of vitamins B1, B12, C and folate and calcium, copper, magnesium and zinc at baseline were within normal ranges. The MVMS group had a greater change in nutrient status after 16 wk compared to the placebo group for serum folate (7.5 vs. -1.6 ng/mL, p < 0.0001), vitamin B12 (159.2 vs. -33.9 pg/mL, p = 0.007), and plasma vitamin C (0.2 vs. 0.0 mg/dL, p = 0.004). Other measured vitamins and minerals were not significantly changed during the intervention. In conclusion, the status of vitamins B12, C and folate improved with MVMS but remained within normal ranges in older adults taking diuretics, metformin, and/or PPIs.

Near-total mandibular reconstruction following osteoradionecrosis with double scapula tip free flap: A case report.

Near-total mandibular reconstruction poses many challenges to reconstructive surgeons. The purpose of this article is to present a challenging case in a patient with osteoradionecrosis of the mandible requiring a near-total mandibular reconstruction using bilateral scapula tip free tissue reconstruction. A 68-year-old African-American male with a history of T2N0M0 squamous cell carcinoma of the tonsil presented with advanced stage osteoradionecrosis of the mandible. Reconstruction was planned using 3D Systems (Denver, CO), mandibular osteotomies were planned inferior to the sigmoid notch on the ascending rami. Neither fibula flap was amenable for harvesting due to poor vasculature of the patient's lower extremities, and bilateral scapula tip free flaps were subsequently planned. The post-operative course was complicated by venous congestion in the right scapula flap which required revision to the venous anastomosis on POD 1. The patient had intraoral breakdown that required debridement in the operating room and application of a cellular matrix. The patient fully recovered from the acute surgery and was discharged home without a tracheostomy. At the last follow up visit, the patient was taking 100% of diet peroral and had no signs of oral incompetence, mental projection was satisfactory, and the ability to verbally communicate was unimpaired. We report a complex case of near-total mandibular reconstruction using simultaneous bilateral scapula tip free flaps. While we do not advocate simultaneous bilateral scapula tip free flaps as the standard of care for large mandibulectomy defects, it may be considered for patients in which traditional osseous free flaps are not available.

Gut Microbiota-Informed Precision Nutrition in the Generally Healthy Individual: Are We There Yet?

Since next generation sequencing facilitated high-throughput and cost-efficient genomics analyses, the human gut metagenome has become an emerging frontier to explore toward precision nutrition. Significant progress has been made in identifying gut microbial features associated with a wide spectrum of human disease. However, other than a few microbiome-disease relations, there is a dearth of confirmed causal inferences, particularly in generally healthy populations. The relatively high unexplained variability in microbiome compositions in this group warrants caution in applying this complex biomarker toward precision nutrition, because our understanding of what constitutes a healthy microbiome is still rudimentary. Although gut microbiota harbor integrated environmental and host-specific information with the potential to facilitate personalized nutritional and lifestyle advice, these data cannot yet be confidently interpreted toward precise recommendations. Thus, nutritional advice for generally healthy individuals based on personal microbiome composition analysis might not yet be appropriate unless accompanied by established blood and physiological biomarkers.

Beyond Nutrient Deficiency-Opportunities to Improve Nutritional Status and Promote Health Modernizing DRIs and Supplementation Recommendations.

The US Dietary Guidelines for Americans (DGA) provide dietary recommendations to meet nutrient needs, promote health, and prevent disease. Despite 40 years of DGA, the prevalence of under-consumed nutrients continues in the US and globally, although dietary supplement use can help to fill shortfalls. Nutrient recommendations are based on Dietary Reference Intakes (DRIs) to meet the nutrient requirements for nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group and many need to be updated using current evidence. There is an opportunity to modernize vitamin and mineral intake recommendations based on biomarker or surrogate endpoint levels needed to 'prevent deficiency' with DRIs based on ranges of biomarker or surrogate endpoints levels that support normal cell/organ/tissue function in healthy individuals, and to establish DRIs for bioactive compounds. We recommend vitamin K and Mg DRIs be updated and DRIs be established for lutein and eicosapentaenoic and docosahexaenoic acid (EPA + DHA). With increasing interest in personalized (or precision) nutrition, we propose greater research investment in validating biomarkers and metabolic health measures and the development and use of inexpensive diagnostic devices. Data generated from such approaches will help elucidate optimal nutrient status, provide objective evaluations of an individual's nutritional status, and serve to provide personalized nutrition guidance.