Acupuncture in Sports Medicine.

Acupuncture is gaining popularity and wider acceptance as a treatment modality within the field of sports medicine. Our objective was to provide a comprehensive review of the existing literature pertaining to acupuncture in sports medicine to shed light on approaches utilized in acupuncture while revealing its personalized nature and its impact on athletes' preparation, performance, and recovery. We evaluated acupuncture research in the context of medicine and sports-related injury treatment, assessing its impact on athletic performance across demographics of athletes. Athletes participating in most sports have shown positive outcomes from acupuncture interventions. Acupuncture improves peak oxygen levels, maximum heart rate, delayed-onset muscle soreness, pain, swelling, explosive force production, and joint mobility. Furthermore, the efficacy of acupuncture appears to be similar regardless of age and sex. Lastly, the acceptance of acupuncture is influenced by cultural factors, with Western and traditional East Asian cultures exhibiting distinct perspectives on its rationale and mechanisms of action. Traditional East Asian acupuncturists typically employ qi and meridian theories in their acupuncture practices, with the recent incorporation of Western concepts. Acupuncture shows promise as an effective treatment for musculoskeletal pain and neuropathies in athletes across different age groups and for addressing injuries in various sports. Our comprehensive review will enhance our understanding of acupuncture's potential as a complementary or distinct therapeutic approach compared to conventional therapies. Additionally, our review explores its specific applications within different sports and delves into the cultural dimensions involved in integrating this practice into modern sports medicine.

The Need for Culturally Appropriate Food Allergy Management Strategies: The Indian Milk Ladder.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and, with a few exceptions, presents in the first few months of life. Baked-milk-containing diets are well tolerated in the majority of milk-allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to an infant's diet in small amounts may enhance the outgrowth of their milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. METHODS: We convened an expert group to develop a comprehensive milk ladder based on the calculated milk protein content of Indian foods. To validate the milk ladder, the foods chosen for the ladder were analyzed and the ladder was re-evaluated based on the cooked milk protein content. RESULTS: Combining expert consensus and validation of milk protein content, we created the world's first milk ladder containing Indian foods. This is the first ladder that provides information on the timing and temperature of cooking, with validated milk protein content. CONCLUSIONS: This is the first milk ladder based on the unique features of Indian food habits built by the consensus of Indian experts along with international collaboration with laboratory quantification of milk protein in each step. We believe the "The Indian Milk Ladder" will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India, but in countries world-wide where these foods are commonly consumed.

Optimizing Maternal Nutrition: The Importance of a Tailored Approach.

Improving nutritional status during pregnancy is a global interest. Frequently, women either fail to meet or exceed nutrient recommendations. Current strategies to improve maternal nutrition focus on a "one-size-fits-all" approach and fail to consider individual factors that affect the mother's overall nutritional status. The objectives of this review were to determine the importance of key nutrients for optimal maternal and fetal health, to explore to what extent current recommendations consider individual factors, and to explore novel strategies to close the gap between current guidelines and real-world challenges through more personalized approaches. This review intercalated different nutritional guidelines and recent scientific publications and research initiatives related to maternal nutrition. Based on that, an overview of current recommendations, challenges related to present approaches, and perspectives for future directions are described. Current guidelines are not optimally supporting adequate nutrient intake and health of expectant mothers and their offspring. Existing recommendations are not consistent and do not sufficiently take into account how interindividual variation leads to differences in nutrient status. Personalized nutrition offers women the opportunity to improve their health by using strategies that are tailored to their unique nutritional needs. Such strategies can include personalized supplementation, holistic lifestyle interventions, digital and application-based technologies, and dietary assessment through blood biomarker and genetic analysis. However, these approaches warrant further investigation and optimization. More personalized approaches have the potential to optimize mothers' and their offspring's health outcomes more appropriately to their nutritional needs before, during, and after pregnancy. Moving away from a generalized "one-size-fits-all" approach can be achieved through a variety of means. Future aims should be to provide supporting evidence to create customized subpopulation-based or individualized recommendations, improve nutrition education, and develop novel approaches to improve adherence to dietary and lifestyle interventions.

Interruptive Electronic Alerts for Choosing Wisely Recommendations: A Cluster Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of interruptive electronic alerts in improving adherence to the American Board of Internal Medicine's Choosing Wisely recommendations to reduce unnecessary laboratory testing. MATERIALS AND METHODS: We administered 5 cluster randomized controlled trials simultaneously, using electronic medical record alerts regarding prostate-specific antigen (PSA) testing, acute sinusitis treatment, vitamin D testing, carotid artery ultrasound screening, and human papillomavirus testing. For each alert, we assigned 5 outpatient clinics to an interruptive alert and 5 were observed as a control. Primary and secondary outcomes were the number of postalert orders per 100 patients at each clinic and number of triggered alerts divided by orders, respectively. Post hoc analysis evaluated whether physicians experiencing interruptive alerts reduced their alert-triggering behaviors. RESULTS: Median postalert orders per 100 patients did not differ significantly between treatment and control groups; absolute median differences ranging from 0.04 to 0.40 for PSA testing. Median alerts per 100 orders did not differ significantly between treatment and control groups; absolute median differences ranged from 0.004 to 0.03. In post hoc analysis, providers receiving alerts regarding PSA testing in men were significantly less likely to trigger additional PSA alerts than those in the control sites (Incidence Rate Ratio 0.12, 95% CI [0.03-0.52]). DISCUSSION: Interruptive point-of-care alerts did not yield detectable changes in the overall rate of undesired orders or the order-to-alert ratio between active and silent sites. Complementary behavioral or educational interventions are likely needed to improve efforts to curb medical overuse. CONCLUSION: Implementation of interruptive alerts at the time of ordering was not associated with improved adherence to 5 Choosing Wisely guidelines. TRIAL REGISTRATION: NCT02709772.

Nutrition as Therapy in Liver Disease.

PURPOSE: The importance of nutrition is often underrecognized in the routine clinical care of patients with chronic liver disease. Nutrition therapy plays a significant role in the management of alcohol-related liver disease and nonalcoholic fatty liver disease. In patients with cirrhosis from any etiology, malnutrition and sarcopenia are directly related to mortality, and nutritional interventions play an important role in the management of these patients. This review explores the role of nutritional intervention as adjuvant therapy across all chronic liver disease. METHODS: A narrative, qualitative systematic review was performed via searches of PubMed for nutritional aspects in the care of chronic liver disease. FINDINGS: Nutritional therapy plays a critical role in the management of chronic liver disease. In nonalcoholic fatty liver disease, specific macronutrient management can lead to weight loss and improved outcomes in these patients. In patients with alcohol-related liver disease, chronic cholestatic liver disease, and decompensated cirrhosis, caloric and protein intake plays a vital role improving outcomes in these patients. Micronutrient deficencies are also common in these patients and require supplementation to prevent other complications of malnutrition. Assessment and management of nutrition should accompany the typical care plan of patients with chronic liver disease. IMPLICATIONS: This review of nutritional therapy in chronic liver disease highlights the current evidence-based and societal recommendations of macronutrient and micronutrient management across the spectrum of all chronic liver disease.

PET/CT scan and biopsy-driven approach for safe anti-PD-1 therapy discontinuation in patients with advanced melanoma.

BACKGROUND: Limited data exist on safe discontinuation of antiprogrammed cell death protein 1 (PD-1) therapy in responding patients with advanced melanoma. The use of 18fluorodeoxyglucose (18FDG)-PET/CT scan and tumor biopsy for assessment of active disease may be an effective predictive biomarker to guide such treatment decisions. METHODS: A retrospective study of 122 patients with advanced melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anticytotoxic T-lymphocyte-associated protein 4 combination therapy at Georgetown Lombardi Comprehensive Cancer Center was conducted. Uveal melanoma patients and those receiving concurrent experimental therapy were excluded. Baseline characteristics, treatment outcomes, and survival were analyzed. Patients who decided to come off treatment typically after 12 months using CT scan radiographic complete response (CR), 18FDG-PET/CT scan complete metabolic response (CMR) or tumor biopsy of a non-CR/CMR tumor site negative for active disease (possible pathological CR) were identified and compared with patients who discontinued treatment due to toxicity while their disease was in control. Event-free survival (EFS) was assessed from the last dose of anti-PD-1 therapy to progression requiring subsequent treatment (surgery, radiation, and/or systemic therapy) or referral to hospice/death due to melanoma. RESULTS: 24 (20%) patients discontinued treatment by choice with no active disease and 28 (23%) patients discontinued treatment due to toxicity with disease control after 12-month and 4-month median treatment durations, respectively. Similar baseline characteristics were observed between cohorts except higher prior receipt of ipilimumab (29% vs 7%; p=0.036) and fewer BRAF mutant positive disease (17% vs 41%; p=0.064) in patients off treatment by choice. Three-year EFS rates were 95% and 71%, respectively. No significant associations between EFS and sex, disease stage, lactate dehydrogenase elevation, BRAF status, prior systemic therapy, ECOG performance status, presence of brain metastases, or combination versus monotherapy were observed. Tumor biopsies led to alternative management in 3/10 patients due to active metastatic melanoma or second malignancy. CONCLUSIONS: Anti-PD-1 therapy discontinuation after 12 months when no active disease is observed on CT scan, PET/CT scan or tumor biopsy may have low rates of disease relapse in patients with advanced melanoma. Biopsy of residual disease may frequently lead to a change in management. These findings are undergoing validation in the EA6192 trial.

WALANT Hand Surgery Does Not Require Postoperative Opioid Pain Management.

BACKGROUND: Currently, opioids are the standard of care for postoperative pain management. Avoiding unnecessary opioid exposure in patients is of current interest because of widespread abuse. METHODS: This is a prospective cohort study in which wide-awake, local anesthesia, no-tourniquet (WALANT) technique was used for 94 hand/upper extremity surgical patients and compared to patient cohorts undergoing similar procedures under monitored anesthesia care. Patients were not prescribed opioids postoperatively but were instead directed to use over-the-counter pain relievers. Pain scores on a visual analogue scale were collected from patients preoperatively, and on postoperative days 1 and 14. WALANT visual analogue scale scores were compared to those of the two patient cohorts who either did or did not receive postoperative opioids after undergoing similar procedures under monitored anesthesia care. Electronic medical records and New York State's prescription monitoring program, Internet System for Tracking Over-Prescribing, were used to assess prescription opioid-seeking. Information on sex, age, comorbidity burden, previous opioid exposure, and insurance coverage was also collected. RESULTS: Decreased pain was reported by WALANT patients 14 days postoperatively compared to preoperatively and 1 day postoperatively, with a total group mean pain score of 0.37. This is lower than mean scores of monitored anesthesia care patients with and without postoperative opioids. Only two WALANT patients (2.1 percent) sought opioid prescriptions from outside providers. There was little evidence suggesting factors including sex, age, comorbidity burden, previous opioid exposure, or insurance status alter these results. CONCLUSION: WALANT may be a beneficial technique hand surgeons may adopt to mitigate use of postoperative opioids and reduce risk of abuse in patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

In the Age of Viral Pandemic, Can Ingredients Inspired by Human Milk and Infant Nutrition Be Repurposed to Support the Immune System?

In 2020, with the advent of a pandemic touching all aspects of global life, there is a renewed interest in nutrition solutions to support the immune system. Infants are vulnerable to infection and breastfeeding has been demonstrated to provide protection. As such, human milk is a great model for sources of functional nutrition ingredients, which may play direct roles in protection against viral diseases. This review aims to summarize the literature around human milk (lactoferrin, milk fat globule membrane, osteopontin, glycerol monolaurate and human milk oligosaccharides) and infant nutrition (polyunsaturated fatty acids, probiotics and postbiotics) inspired ingredients for support against viral infections and the immune system more broadly. We believe that the application of these ingredients can span across all life stages and thus apply to both pediatric and adult nutrition. We highlight the opportunities for further research in this field to help provide tangible nutrition solutions to support one's immune system and fight against infections.

The impact of the elimination diet on growth and nutrient intake in children with food protein induced gastrointestinal allergies.

BACKGROUND: Non immunoglobulin E (IgE) mediated allergies affecting the gastrointestinal tract require an elimination diet to aid diagnosis. The elimination diet may entail multiple food eliminations that contribute significantly to macro- and micro-nutrient intake which are essential for normal growth and development. Previous studies have indicated growth faltering in children with IgE-mediated allergy, but limited data is available on those with delayed type allergies. We therefore performed a study to establish the impact on growth before and after commencing an elimination diets in children with food protein induced non-IgE mediated gastrointestinal allergies. METHODS: A prospective, observational study was performed at the tertiary gastroenterology department. Children aged 4 weeks-16 years without non-allergic co-morbidities who were required to follow an elimination diet for suspected food protein induced gastrointestinal allergies were included. Growth parameters pre-elimination were taken from clinical notes and post-elimination measurements (weight and height) were taken a minimum of 4 weeks after the elimination diet. A 3-day estimated food diary was recorded a minimum of 4 weeks after initiating the elimination diet, including also any hypoallergenic formulas or over the counter milk alternatives that were consumed. RESULTS: We recruited 130 children: 89 (68.5 %) boys and a median age of 23.3 months [IQR 9.4-69.2]. Almost all children (94.8 %) in this study eliminated CM from their diet and average contribution of energy in the form of protein was 13.8 % (SD 3.9), 51.2 % (SD 7.5) from carbohydrates and 35 % (SD 7.5) from fat. In our cohort 9 and 2.8 % were stunted and wasted respectively. There was a statistically significant improvement in weight-for-age (Wtage) after the 4 week elimination diet. The elimination diet itself did not improve any of the growth parameters, but achieving energy and protein intake improved Wtage and WtHt respectively, vitamin and/or mineral supplements and hypoallergenic formulas were positively associated with WtHt and Wtage. CONCLUSION: With appropriate dietary advice, including optimal energy and protein intake, hypoallergenic formulas and vitamins and mineral supplementation, growth parameters increased from before to after dietary elimination. These factors were positively associated with growth, irrespective of the type of elimination diet and the numbers of foods eliminated.

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors.

The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates.

Nutritional status in children with Shwachman-diamond syndrome.

OBJECTIVE: In Shwachman-Diamond syndrome (SDS), pancreatic insufficiency can lead to malabsorption of fat-soluble vitamins and trace elements. The aim of this study was to assess the serum concentrations of vitamins A and E, zinc, copper, and selenium and their deficiencies. METHODS: This retrospective review was performed in 21 children (12 were male; median age, 7.8 years) with genetically confirmed SDS at a tertiary pediatric hospital. Pancreatic enzyme replacement therapy (PERT) and vitamin or trace elements supplements were documented. RESULTS: Twenty patients (95%) had pancreatic insufficiency receiving PERT, 10 (47%) had a combined vitamin and trace element deficiency, 6 (29%) had an isolated vitamin deficiency, and 4 (19%) had an isolated trace element deficiency. Vitamins A and E deficiency occurred in 16 (76%) and 4 (19%) of 21, respectively. Low serum selenium was found in 10 (47%), zinc deficiency in 7 (33%), and copper deficiency in 5 (24%). Eleven patients (52%) were on multivitamin supplementation, and 2 (10%) on zinc and selenium supplements. No statistical differences were found between repeated measurements for all micronutrients. CONCLUSIONS: More than 50% of the children had vitamin A and selenium deficiencies despite adequate supplementation of PERT and supplements. Micronutrients should be routinely measured in SDS patients to prevent significant complications.

A practical approach to vitamin and mineral supplementation in food allergic children.

BACKGROUND: The management of food allergy in children requires elimination of the offending allergens, which significantly contribute to micronutrient intake. Vitamin and mineral supplementation are commonly suggested as part of dietary management. However a targeted supplementation regime requires a complete nutritional assessment, which includes food diaries. Ideally these should be analysed using a computerised program, but are very time consuming. We therefore set out to evaluate current practice of vitamin and mineral supplementation in a cohort of children with non-Immunoglobulin E (IgE) mediated food allergies. METHODS: This prospective, observational study recruited children aged 4 weeks - 16 years, who required to follow an elimination diet for non-IgE mediated allergies. Only children that improved according to a symptom score and were on a vitamin and/or mineral supplement were included. A 3-day food diary including vitamin and mineral supplementation was recorded and analysed using Dietplan computer program. We assessed dietary adequacy with/without the supplement using the Dietary Reference Values. RESULTS: One hundred-and-ten children had completed food diaries and of these 29% (32/110) were taking vitamin and/or mineral supplements. Children on hypoallergenic formulas were significantly (p = 0.007) less likely to be on supplements than those on alternative over-the-counter milks. Seventy-one percent had prescribable supplements, suggested by a dietitian/physician. Sixty percent of those without a vitamin supplement had a low vitamin D intake, but low zinc, calcium and selenium was also common. Of the supplemented cohort many continued to be either under or over-supplemented. CONCLUSION: This study has raised the question for the first time, whether clinicians dealing with paediatric food allergies should consider routine vitamin and/or mineral supplements in the light of deficient intake being so common in addition to being so difficult to predict.

Dietary elimination of children with food protein induced gastrointestinal allergy - micronutrient adequacy with and without a hypoallergenic formula?

BACKGROUND: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. METHOD: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). RESULTS: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. CONCLUSION: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies.

Integrating current treatment options for TKI-resistant chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for approximately 10% of new cases of leukemia. The introduction of tyrosine kinase inhibitors (TKIs) has led to a reduction in mortality rates, and the estimated prevalence of CML is increasing accordingly. Most patients with CML are diagnosed in the chronic phase, and approximately 15% to 30% of these patients will meet some definition of resistance to imatinib. In the more advanced phases of disease, the rates of imatinib resistance are much higher. Both the National Comprehensive Cancer Network (NCCN) and the European LeukemiaNet (ELN) guidelines emphasize adequate monitoring of patients to ensure that they are meeting treatment milestones. Loss of response is most commonly associated with the acquisition of resistance-conferring kinase domain point mutations within BCR-ABL1. The multiple treatment options available for patients with imatinib-resistant CML include dasatinib, nilotinib, bosutinib, and ponatinib, as well as the non-TKI salvage agent omacetaxine mepesuccinate. Treatment selection is based on factors such as the patient's disease state, prior therapies, comorbidities, treatment toxicity, and goals of therapy. This clinical roundtable monograph provides expert discussion on the monitoring of TKI-resistant CML, when to change therapy, and how to select the best treatment option.

The RCPCH care pathway for food allergy in children: an evidence and consensus based national approach.

AIMS: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies; food allergy is the second pathway. The pathways focus on defining the competences required to improve the equity of care received by children with allergic conditions. METHOD: The food allergy pathway was developed by a multidisciplinary working group and was based on a comprehensive review of the evidence. The pathway was reviewed by a broad group of stakeholders including the public and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. The National Institute of Health and Clinical Excellence simultaneously established a short guideline review of community practice for children with food allergy; close communication was established between the two groups. RESULTS: The results are presented in two sections: a pathway algorithm and the competences. The entry points are defined and the ideal pathway of care is described from initial recognition and confirmed diagnosis through to follow-up. CONCLUSIONS: The range of manifestations of food allergy/intolerance is much more diverse than hitherto recognised and diagnosis can be problematic as many patients do not have classical IgE mediated disease. The pathway provides a guide for training and development of services to facilitate improvements in delivery as close to the patient's home as possible. The authors recommend that this pathway is implemented locally by a multidisciplinary team with a focus on creating networks.

Dasatinib.

Dasatinib is an orally bioavailable potent inhibitor of multiple tyrosine kinases, including ABL and SRC. Preclinical studies have shown dasatinib to be a much more potent inhibitor of BCR-ABL than imatinib is, and to harbor efficacy against nearly all imatinib-resistant BCR-ABL mutants. Phase I clinical studies have been conducted in imatinib-resistant and -intolerant chronic myeloid leukemia and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. No dose-limiting toxicity was observed at doses that harbored substantial clinical efficacy. Multinational phase II studies have confirmed the phase I experience and have led to accelerated approval by the U.S. Food and Drug Administration for the treatment of imatinib-resistant and -intolerant chronic myeloid leukemia as well as its full approval for the treatment of therapy-resistant Ph+ acute lymphoblastic leukemia.