Independent effects of volume and energy density manipulation on energy intake and appetite in healthy adults: A randomized, controlled, crossover study.

Consuming enough energy to meet high energy demands can be challenging for military personnel wherein logistical constraints limit food availability. Increasing dietary energy density (ED) and/or volume density (VD) of rations may be countermeasures, but whether positive linear associations between ED and energy intake (EI) hold at moderate-to-high ED and VD is unclear. This study examined the effects of covertly increasing the ED and VD of moderate ED (≥1.6 kcal/g) foods on appetite and energy intake. Twenty healthy men completed four 2-day treatments in random order by consuming a standardized diet containing three experimental food items (EXP) engineered using leavening, physical compression and fat manipulation to be isovolumetric but lower (L) or higher (H) in ED and VD creating four treatments: LED/LVD, LED/HVD, HED/LVD, HED/HVD. Consumption of EXP was compulsory during two meals and a snack, but remaining intake was self-selected (SSF). Results failed to show any ED-by-VD interactions. During LVD, EI was lower for EXP (-417 kcal [95%CI: 432, -402], p < 0.01) and TOTAL (SSF + EXP) (-276 kcal [95%CI: 470, -83], p = 0.01) compared to HVD, while SSF EI did not differ (140 kcal [-51, 332], p = 0.15). During LED, EI for EXP (-291 kcal [95%CI: 306, -276], p < 0.01) was lower than HED, while SSF EI was higher than HED (203 kcal 95%CI: [12, 394], p = 0.04) and TOTAL EI did not differ (-88 kcal [-282, 105], p = 0.36). Thus, when a small isovolumetric portion of the diet was manipulated, increasing the VD of moderate ED foods failed to elicit compensatory reductions in ad libitum EI while increasing the ED of moderate ED foods did. Findings may support VD manipulation of moderate ED foods as a strategy to promote increased short-term EI in environments wherein logistical burden may limit food volume.

Factors associated with increased 30-day re-operation risk in anterior cruciate ligament reconstruction.

BACKGROUND: Revision surgery following isolated anterior cruciate ligament reconstruction (ACLR) has often focused on mid- to long-term revisions due to re-rupture, while short-term 30-day revision is a rare, but underappreciated entity. This study aims to characterize incidence and risk factors for reoperations following isolated ACLR. METHODS: This is a retrospective case-control analysis of the American College of Surgeons National Surgical Quality Improvement Program Database (NSQIP) database from 2005 to 2017. Current Procedural Terminology codes were used to identify elective isolated ACLR patients. Patients undergoing reoperations were analyzed using bivariate analysis against their respective perioperative variables. Multivariate stepwise logistic regression was used to identify independent risk factors for reoperations after ACLR. RESULTS: 12,790 patients were included in the study. 37.0% of patients were female. Mean age was 32.2+/-10.7 years and mean body mass index (BMI) was 27.8+/-6.5 kg/m2, with 28.9% of patients with BMI > 30. The most frequently reported reason for reoperation based on CPT and ICD-9/10 codes was postoperative infection (0.5%). Overall reoperation rate was approximately 0.5%. Multivariate analysis identified operative time >1.5 h (OR 2.6 [95% CI; 1.5-4.4]), dependent functional status (OR 14.0 [1.4-141.6]), and adjunctive anesthesia (OR 2.4 [95% CI; 1.1-5.0]) as independent risk factors for reoperation. Female sex was a protective factor against reoperations (OR 0.6 [0.3-0.98]). CONCLUSION: Primary, isolated ACLR is associated with extremely low rates of short-term reoperations. Operative time >1.5 h, dependent functional status, and adjunctive anesthesia were independent risk factors for reoperation and female sex was a protective factor against reoperation. LEVEL OF EVIDENCE: Level III. Retrospective cohort study.

Dialysis decision-making process by Chinese American patients at an urban, academic medical center: a retrospective chart review.

BACKGROUND: Clinical practice guidelines emphasize shared decision-making for kidney replacement treatment, yet little is known about the influence of cultural differences on that process. We undertook a retrospective chart review to explore the process and timing of dialysis decision making and initiation in Chinese American patients to provide quality kidney care for this population. DESIGN: Participants received outpatient care at Tufts Medical Center and dialysis at Dialysis Clinic, Inc. Boston or Somerville, MA from 2001-2021. Clinic chart review sourced demographic, clinical, and end-of-life care information from 180 participants (82 Chinese American, 98 other) from stage 4 chronic kidney disease (CKD) and dialysis initiation. RESULTS: Chinese American participants were older (mean 70 vs. 59, p < 0.0001), less likely to speak English (12% vs. 87%, p < 0.0001), and used interpreter services more (80% vs. 11%, p < 0.0001). Chinese American participants had more visits (median 14 vs. 10, p = 0.005); were more often accompanied by family members (75% vs. 40%, p < 0.001); and had significantly lower rates of healthcare proxy documentation (35% vs. 55%, p = 0.006). There was no statistical difference in months between first CKD 4 visit and first dialysis. Both groups started dialysis at the same average eGFR and with similar rates of permanent dialysis access. Chinese American participants had significantly lower serum albumin at dialysis initiation (mean 3.3 g/dL vs 3.7 g/dL, p = 0.0003). Documentation reflected a low number of conversations about non-dialytic care, end-of-life planning, or palliative care in both groups across all visits. CONCLUSION: The time between CKD 4 and dialysis initiation was the same in both groups, suggesting a similar overall outcome of care. Chart documentation suggests that Chinese American participants had a significantly higher number of visits with nephrologists where discussion about dialysis was noted and were more likely to have a family member present at the visit. Fewer Chinese American participants completed healthcare proxies. Among all study participants, healthcare proxy, code status, and palliative care discussions were reported less frequently than expected. These findings highlight opportunities for collaboration between palliative care clinicians and nephrologists.

Tretinoin Enhances the Effects of Chemotherapy in Juvenile Myelomonocytic Leukemia Using an Ex Vivo Drug Sensitivity Assay.

PURPOSE: Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric malignancy with myelodysplastic and myeloproliferative features. Curative treatment is restricted to hematopoietic stem-cell transplantation. Fludarabine combined with cytarabine (FLA) and 5-azacitidine (AZA) monotherapy are commonly used pre-transplant therapies. Here, we present a drug screening strategy using a flow cytometry-based precision medicine platform to identify potential additional therapeutic vulnerabilities. METHODS: We screened 120 dual- and 10 triple-drug combinations (DCs) on peripheral blood (n = 21) or bone marrow (n = 6) samples from 27 children with JMML to identify DCs more effectively reducing leukemic cells than the DCs' components on their own. If fewer leukemic cells survived a DC ex vivo treatment compared with that DC's most effective component alone, the drug effect was referred to as cooperative. The difference between the two resistant fractions is the effect size. RESULTS: We identified 26 dual- and one triple-DC more effective than their components. The differentiation agent tretinoin (TRET; all-trans retinoic acid) reduced the resistant fraction of FLA in 19/21 (90%) samples (decrease from 15% [2%-61%] to 11% [2%-50%] with a mean effect size of 3.8% [0.5%-11%]), and of AZA in 19/25 (76%) samples (decrease from 69% [34%-100+%] to 47% [17%-83%] with a mean effect size of 16% [0.3%-40%]). Among the resistant fractions, the mean proportion of CD38+ cells increased from 7% (0.03%-25%; FLA) to 17% (0.3%-38%; FLA + TRET) or from 10% (0.2%-31%; AZA) to 51% (0.8%-88%; AZA + TRET). CONCLUSION: TRET enhanced the effects of FLA and AZA in ex vivo assays with primary JMML samples.

Is Cannabis Effective in the Treatment of Chronic Back Pain?

Cannabis is commonly recognized as a recreational substance. It has been explored for its potential therapeutic applications in addressing various conditions, such as depression, anxiety, sleep disorders, neurological disorders, and chronic low back pain, which affect a significant portion of the population. In the United Kingdom, cannabis has been recognized and licensed for medical use since November 2018, with about 12 National Health Service prescriptions in circulation largely due to patient pressure, with support from media campaigns for its use when there was growing evidence of its use in intractable epilepsy. Cannabis is beginning to gain traction as an alternative or even a complementary drug to opiates with some pre-clinical studies showing opiate-sparing effects. Despite references to its therapeutic use, cannabis as a therapeutic drug has been controversial due to the negative perception of its use as a recreational drug. As a result, there have been challenges in changing the perception of healthcare authorities and clinicians on the use of cannabis as a therapeutic tool for pain relief. The stigma associated with cannabis could be responsible for the paucity of randomized controlled trials on the efficacy of medical cannabis, further decreasing the credibility of the few trials conducted.

Ex Vivo Drug Sensitivity Correlates with Clinical Response and Supports Personalized Therapy in Pediatric AML.

Acute myeloid leukemia (AML) is a heterogeneous disease that accounts for ~20% of all childhood leukemias, and more than 40% of children with AML relapse within three years of diagnosis. Although recent efforts have focused on developing a precise medicine-based approach towards treating AML in adults, there remains a critical gap in therapies designed specifically for children. Here, we present ex vivo drug sensitivity profiles for children with de novo AML using an automated flow cytometry platform. Fresh diagnostic blood or bone marrow aspirate samples were screened for sensitivity in response to 78 dose conditions by measuring the reduction in leukemic blasts relative to the control. In pediatric patients treated with conventional chemotherapy, comprising cytarabine, daunorubicin and etoposide (ADE), ex vivo drug sensitivity results correlated with minimal residual disease (r = 0.63) and one year relapse-free survival (r = 0.70; AUROC = 0.94). In the de novo ADE analysis cohort of 13 patients, AML cells showed greater sensitivity to bortezomib/panobinostat compared with ADE, and comparable sensitivity between venetoclax/azacitidine and ADE ex vivo. Two patients showed a differential response between ADE and bortezomib/panobinostat, thus supporting the incorporation of ex vivo drug sensitivity testing in clinical trials to further evaluate the predictive utility of this platform in children with AML.

Eliciting Activity Goals With a Self-Administered Survey Among Patients With Hip or Knee Osteoarthritis.

Background: Success of treatment for hip or knee osteoarthritis (OA) should be evaluated relative to patients' personal activity goals. Questions/Purposes: We sought to ascertain important principles for collecting such goals and developed a survey informed by those principles to facilitate better shared decision-making. Methods: From a series of 100 patient interviews inquiring about specific activity goals, we identified 6 principles for goal collection that are important to patients and physicians and could practically facilitate better shared decision-making (phase 1). Incorporating these principles, we designed a self-administered survey to measure specific pretreatment activity goals, piloting in 1 surgeon's office (phase 2). During office visits, the feasibility of achieving stated goals was discussed between the surgeon and the patient, and goal modifications were recorded. Results: The phase 2 survey was administered to 252 patients, among whom 130 were women (51.6%); 215 (85.3%), white; mean age, 58.5 years; mean body mass index, 30.2 kg/m2; and 92.9% had 1 or more goals, totaling 106 unique goals. Patient demographics were associated with having goals for walking, running, exercising, golfing, tennis, and stairs. Hip and knee patients could last perform their goal on average 21.7 and 38.6 months prior (P = .002). Patient and surgeon agreed to modify goals 19% of the time, more often among younger patients (P = .001) and for running (64% modified, P < .0001) and skiing (42%, P = .0026), but less often for walking (14%, P = .0430) and golf (0%, P = .0204). Conclusions: Patients' activity goals can be captured by a self-administered survey, collected before an office visit, and used to facilitate shared decision-making.

Oral anticoagulants: a systematic overview of reviews on efficacy and safety, genotyping, self-monitoring, and stakeholder experiences.

BACKGROUND: This systematic overview was commissioned by England's Department of Health and Social Care (DHSC) to assess the evidence on direct (previously 'novel') oral anticoagulants (OACs), compared with usual care, in adults, to prevent stroke related to atrial fibrillation (AF), and to prevent and treat venous thromboembolism (VTE). Specifically, to assess efficacy and safety, genotyping, self-monitoring, and patient and clinician experiences of OACs. METHODS: We searched MEDLINE, Embase, ASSIA, and CINAHL, in October, 2017, updated in November 2021. We included systematic reviews, published from 2014, in English, assessing OACs, in adults. We rated review quality using AMSTAR2 or the JBI checklist. Two reviewers extracted and synthesised the main findings from the included reviews. RESULTS: We included 49 systematic reviews; one evaluated efficacy, safety, and cost-effectiveness, 17 assessed genotyping, 23 self-monitoring or adherence, and 15 experiences (seven assessed two topics). Generally, the direct OACs, particularly apixaban (5 mg twice daily), were more effective and safer than warfarin in preventing AF-related stroke. For VTE, there was little evidence of differences in efficacy between direct OACs and low-molecular-weight heparin (prevention), warfarin (treatment), and warfarin or aspirin (secondary prevention). The evidence suggested that some direct OACs may reduce the risk of bleeding, compared with warfarin. One review of genotype-guided warfarin dosing assessed AF patients; no significant differences in stroke prevention were reported. Education about OACs, in patients with AF, could improve adherence. Pharmacist management of coagulation may be better than primary care management. Patients were more adherent to direct OACs than warfarin. Drug efficacy was highly valued by patients and most clinicians, followed by safety. No other factors consistently affected patients' choice of anticoagulant and adherence to treatment. Patients were more satisfied with direct OACs than warfarin. CONCLUSIONS: For stroke prevention in AF, direct OACs seem to be more effective and safer than usual care, and apixaban (5 mg twice daily) had the best profile. For VTE, there was no strong evidence that direct OACs were better than usual care. Education and pharmacist management could improve coagulation control. Both clinicians and patients rated efficacy and safety as the most important factors in managing AF and VTE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017084263-one deviation; efficacy and safety were from one review.

Too much of a good thing: A case series of rare yet pertinent causes of hypercalcaemia and acute kidney injury.

Calcium compounds and vitamin D supplements are readily available as over-the-counter preparations. Whilst integral in maintaining calcium homeostasis in certain patients, excess exogenous intake of these preparations can have deleterious effects, particularly in terms of renal function. We look at the cases of two patients, aged 52 and 34, who were referred into hospital with hypercalcaemia and acute kidney injury (AKI). Both individuals reported regular and prolonged self-medication with unregulated over-the-counter supplements containing calcium carbonate and vitamin D, respectively. Prompt investigation and treatment enabled an element of reversibility of the AKI in both the cases, with further improvement in renal function over time. We emphasise the importance of recognising the overuse of exogenous vitamin D supplements and calcium compounds as rare yet treatable causes of AKI associated with hypercalcaemia and discuss how raising public awareness into the risks posed by self-medication of over-the-counter medicines is paramount.

Biosynthesis and characterization of fuscimiditide, an aspartimidylated graspetide.

Microviridins and other ω-ester-linked peptides, collectively known as graspetides, are characterized by side-chain-side-chain linkages installed by ATP-grasp enzymes. Here we report the discovery of a family of graspetides, the gene clusters of which also encode an O-methyltransferase with homology to the protein repair catalyst protein L-isoaspartyl methyltransferase. Using heterologous expression, we produced fuscimiditide, a ribosomally synthesized and post-translationally modified peptide (RiPP). NMR analysis of fuscimiditide revealed that the peptide contains two ester cross-links forming a stem-loop macrocycle. Furthermore, an unusually stable aspartimide moiety is found within the loop macrocycle. We fully reconstituted fuscimiditide biosynthesis in vitro including formation of the ester and aspartimide moieties. The aspartimide moiety embedded in fuscimiditide hydrolyses regioselectively to isoaspartate. Surprisingly, this isoaspartate-containing peptide is also a substrate for the L-isoaspartyl methyltransferase homologue, thus driving any hydrolysis products back to the aspartimide form. Whereas an aspartimide is often considered a nuisance product in protein formulations, our data suggest that some RiPPs have aspartimide residues intentionally installed via enzymatic activity.

Analysis of the Quality, Reliability, and Educational Content of YouTube Videos Concerning Spine Tumors.

BACKGROUND: Given the high volume of user traffic to YouTube, it is important that the medical information disseminated on this platform is of high quality. Unfortunately, previous studies have demonstrated this to not be the case. We aimed to evaluate the quality and educational content of YouTube videos concerning spine tumors using 2 previously validated assessment tools. METHODS: The first 50 videos returned by the keyword search "spine tumor" were included in the study. The JAMA benchmark criteria (range: 0-4) were used to assess video reliability, whereas the Global Quality Score (GQS) (range: 0-5) was used to determine educational quality and content. RESULTS: Videos were primarily authored by academic medical groups (80%), while content was primarily related to disease-specific information (44%) or the patient experience (24%). Surgical treatment options and nonsurgical management were discussed in 66% and 50% of all videos, respectively. Sixty percent of videos reported benefits of treatment, while 44% reported potential risks or complications. The average JAMA score and GQS were 3.1 ± 0.27 (range: 3-4) and 2.6 ± 1.3 (range: 1-5), respectively. Multivariate linear regression analyses revealed that video duration (ß = 0.00697, P = 0.04) and number of views (ß = 0.000018, P = 0.001) were positively associated with JAMA score. Video duration and number of dislikes were associated with higher GQS (ß = 0.041, P = 0.025) and lower GQS (ß = -0.189, P = 0.04), respectively. Lastly, number of days since upload was associated with lower Video Power Index (ß = -0.003, P = 0.003). CONCLUSIONS: The reliability, quality, and educational content of YouTube videos were poor to suboptimal. Physicians should be wary of the education provided by YouTube on spine tumors and guide patients in seeking out additional sources of information. CLINICAL RELEVANCE: YouTube videos are commonly viewed by patients seeking health information on spine tumors. While certain videos may provide useful information, the absence of an editorial process allows videos with poor reliability and low quality to be uploaded. We believe these findings may be useful to physicians seeking ways to better guide their patients with the most appropriate educational tools throughout their disease management.

Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in Dialysis: A Kidney Health Initiative Workgroup Report.

Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to (1) create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, (2) construct a conceptual model for developing and evaluating a skeletal muscle cramping-specific patient-reported outcome measure, and (3) identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.

Patient Reported Outcomes in Metastatic Spine Disease: Concurrent Validity of PROMIS with the Spine Oncology Study Group Outcome Questionnaire.

STUDY DESIGN: Cross-sectional prospective study. OBJECTIVE: To evaluate the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Pain Interference (PI), and Depression domains in comparison to the Spine Oncology Study Group-Outcomes Questionnaire (SOSG-OQ) in patients with metastatic spine disease. SUMMARY OF BACKGROUND DATA: While there remains a significant movement toward incorporating patient-reported outcome measures (PROMs) into clinical care, there are few validated PROMs for patients with metastatic spine disease. The SOSG-OQ was designed and validated for metastatic spine tumor patients. However, the use of general symptom-based PROMs, such as PROMIS domains, may reduce both patient and physician burden and improve interdisciplinary care if shown to be concurrently valid. METHODS: Metastatic spine tumor patients from January 2017 to July 2021 at a single academic medical center were asked to complete PROMIS PF, PI, and Depression domains and the SOSG-OQ. Spearman correlation (p) coefficients were calculated. RESULTS: A total of 103 unique visits, representing 79 patients met our inclusion criteria. A majority were men (59; 57%) and Caucasian (93; 90%), and the average age was 64-years-old (range: 34-87). There were 13 different types of histologies reported, with multiple myeloma, breast cancer, and prostate cancer representing 28 (27%), 26 (25%), and 13 (13%), respectively. Additional cancers included renal cell carcinoma, lung cancer, colon cancer, thyroid cancer, large B-cell lymphoma, nonHodgkin lymphoma, esophageal cancer, plasmacytoma, metastatic paraganglioma, and metastatic spindle cell sarcoma. SOSG-OQ was strongly correlated with PROMIS PI (ρ = 0.78) and PROMIS PF (ρ = 0.71), and moderately correlated with PROMIS Depression (ρ = 0.58). CONCLUSION: PROMIS PF, PI, and Depression appear to capture similar clinical insight as the SOSG-OQ. Spine surgeons can consider using these PROMIS domains in lieu of the SOSG-OQ in metastatic spine tumor patients.Level of Evidence: NA.

Successful treatment and integrated genomic analysis of an infant with FIP1L1-RARA fusion-associated myeloid neoplasm.

FIP1L1-RARA-a ssociated neoplasm is a very rare and aggressive disease, with only 3 previously reported cases in the literature. Here, we describe a 9-month-old boy who presented with a FIP1L1-RARA fusion-associated myelodysplastic/myeloproliferative neoplasm-like overlap syndrome, with similarities and distinct features to both acute promyelocytic leukemia and juvenile myelomonocytic leukemia. Using a combined approach of chemotherapy, differentiating agents, and allogeneic hematopoietic stem cell transplant (allo-HCT), this patient remains in remission 20 months after allo-HCT. To our knowledge, this is only the second published pediatric case involving this condition and the only case with a favorable long-term outcome. Given the aggressive disease described in the previously published case report, as well as the successful treatment course described, the combinatorial use of chemotherapy, differentiation therapy, and allo-HCT for treatment of FIP1L1-RARA fusion-associated myeloid neoplasms should be considered.

Survival of Salmonella enterica in Military Low-Moisture Food Products during Long-Term Storage at 4, 25, and 40°C.

ABSTRACT: Salmonella enterica has been increasingly implicated in foodborne outbreaks involving low-moisture foods (LMF) during the recent decade. This study aimed to investigate the potential for persistence of S. enterica in a range of LMF during storage at three temperatures. LMF products, boil-in-bag eggs (freeze-dried product), chocolate protein drink, cran-raspberry First Strike bars, mocha dessert bar, and peanut butter, were inoculated with a five-strain cocktail of S. enterica and stored at 4, 25, or 40°C for 36 months. Salmonella populations remained above 7 log CFU/g in all products stored at 4°C and above 6 log CFU/g in products stored at 25°C, excluding the cran-raspberry First Strike bars. Storage at 40°C resulted in Salmonella populations above 5.5 log CFU/g in boil-in-bag eggs after 36 months and demonstrated survivability for 12 months or less in the other five products. Additionally, a mocha bar production temperature profile study identified rapid cooling of bars in which the temperatures reached would have no measurable impact on Salmonella populations. The results indicate the ability of Salmonella to survive in a variety of LMF category foods, even under adverse storage conditions and identifies how the food matrix may affect Salmonella survivability. The data indicate the importance of establishing food processing procedures that adequately mitigate the presence of Salmonella throughout food processing systems, while also increasing comprehensive understanding of Salmonella survivability mechanisms.