Development and validation of equations for predicting appendicular skeletal muscle mass in male patients with head and neck cancer and normal hydration status.

OBJECTIVE: Muscle mass is typically assessed by abdominal computed tomography, magnetic resonance imaging, and dual-energy x-ray absorptiometry. However, these tests are not routinely performed in patients with head and neck cancer (HNC), making sarcopenia assessment difficult. The aim of this study was to develop and validate equations for predicting appendicular skeletal muscle mass (ASM) from data obtained in daily medical practice, with bioelectrical impedance analysis (BIA)-measured appendicular skeletal muscle mass (BIA-ASM) as a reference. METHODS: This cross-sectional study included 103 men with HNC who were randomly placed into development and validation groups. The prediction equations for BIA-ASM were developed by multiple regression analysis and validated by Bland-Altman analyses. The estimated skeletal muscle mass index (eSMI) was also statistically evaluated to discriminate the cutoff value for BIA-measured SMI according to the Asian Working Groups for Sarcopenia. RESULTS: Two practical equations, which included 24-h urinary creatinine excretion volume (24hUCrV), handgrip strength (HGS), body weight (BW), and body height (BHt), were developed: ASM (kg) = -39.46 + (3.557 × 24hUCrV [g]) + (0.08872 × HGS [kg]) + (0.1263 × BW [kg]) + (0.2661 × BHt [cm]) if available for 24hUCrV (adjusted R2 = 0.8905), and ASM (kg) = -42.60 + (0.1643 × HGS [kg]) + (0.1589 × BW [kg]) + (0.2807 × BHt [cm]) if not (adjusted R2 = 0.8589). ASM estimated by these two equations showed a significantly strong correlation with BIA-ASM (R > 0.900). Bland-Altman analyses showed a good agreement, and eSMI accuracy was high (>80%) in both equations. CONCLUSIONS: These two equations are a valid option for estimating ASM and diagnosing sarcopenia in patients with HNC in all facilities without special equipment.

Muscle mass, quality, and strength; physical function and activity; and metabolic status in cachectic patients with head and neck cancer.

BACKGROUND & AIMS: Cancer cachexia is commonly associated with poor prognosis in patients with head and neck cancer (HNC). However, its pathophysiology and treatment are not well established. The current study aimed to assess the muscle mass/quality/strength, physical function and activity, resting energy expenditure (REE), and respiratory quotient (RQ) in cachectic patients with HNC. METHODS: This prospective cross-sectional study analyzed 64 patients with HNC. Body composition was measured via direct segmental multifrequency bioelectrical impedance analysis, and muscle quality was assessed using echo intensity on ultrasonography images. Muscle strength was investigated utilizing handgrip strength and isometric knee extension force (IKEF). Physical function was evaluated using the 10-m walking speed test and the five times sit-to-stand (5-STS) test. Physical activity was examined using a wearable triaxial accelerometer. REE and RQ were measured via indirect calorimetry. These parameters were compared between the cachectic and noncachectic groups. RESULTS: In total, 23 (36%) patients were diagnosed with cachexia. The cachectic group had a significantly lower muscle mass than the noncachectic group. Nevertheless, there was no significant difference in terms of fat between the two groups. The cachectic group had a higher quadriceps echo intensity and a lower handgrip strength and IKEF than the noncachectic group. Moreover, they had a significantly slower normal and maximum walking speed and 5-STS speed. The number of steps, total activity time, and time of activity (<3 Mets) did not significantly differ between the two groups. The cachectic group had a shorter time of activity (≥3 Mets) than the noncachectic group. Furthermore, the cachectic group had a significantly higher REE/body weight and REE/fat free mass and a significantly lower RQ than the noncachectic group. CONCLUSIONS: The cachectic group had a lower muscle mass/quality/strength and physical function and activity and a higher REE than the noncachectic group. Thus, REE and physical activity should be evaluated to determine energy requirements. The RQ was lower in the cachectic group than that in the noncachectic group, indicating changes in energy substrate. Further studies must be conducted to examine effective nutritional and exercise interventions for patients with cancer cachexia.

Association of phase angle with muscle function and prognosis in patients with head and neck cancer undergoing chemoradiotherapy.

OBJECTIVES: The aims of this study were to investigate the correlation of phase angle (PhA) with other parameters (e.g., muscle mass/quality/strength and physical function), assess the prognostic relevance of prechemoradiotherapy (CRT) PhA, and suggest a reference value of PhA in Asian patients with head and neck cancer (HNC). METHODS: Ninety-six patients with HNC who underwent CRT were divided into two groups- maintained-PhA group and low-PhA group-according to the PhA 25th percentile values by sex. Pretreatment PhA was measured using direct segmental multifrequency bioelectrical impedance analysis, and muscle quality was assessed using echo intensity in ultrasound images. Correlation of PhA with other parameters was investigated, and between-group differences with respect to adverse events, treatment interruption, and 3-y survival were assessed. RESULTS: PhA showed a positive correlation with isometric knee extension force (R = 0.710), handgrip strength (R = 0.649), skeletal muscle mass index (R = 0.620), and maximum gait speed (R = 0.543; P < 0.001). PhA showed a negative correlation with echo intensity (R = -0.439) and five times sit-to-stand test (R = -0.505; P < 0.01). The low-PhA group had a higher incidence of severe anemia (52% in low-PhA versus 17% in maintained-PhA), aspiration (17 versus 1%), radiotherapy interruption (17 versus 3%), and poor 3-y survival (47 versus 81%) than the maintained-PhA group (P < 0.05). CONCLUSION: PhA was correlated with muscle mass/quality/strength, and physical function. Low PhA was associated with severe adverse events, treatment interruption, and shorter survival. These findings suggested that 4.6° for men and 4° for women may be useful as prognostic reference values in Asian patients with HNC.

Can women in labor give informed consent to epidural analgesia?

There are reasons to believe that decision-making capacity (mental competence) of women in labor may be compromised in relation to giving informed consent to epidural analgesia. Not only severe labor pain, but also stress, anxiety, and premedication of analgesics such as opioids, may influence women's decisional capacity. Decision-making capacity is a complex construct involving cognitive and emotional components which cannot be reduced to 'understanding' alone. A systematic literature search identified a total of 20 empirical studies focused on women's decision-making about epidural analgesia for labor pain. Our review of these studies suggests that empirical evidence to date is insufficient to determine whether women undergoing labor are capable of consenting to epidural analgesia. Given such uncertainties, sufficient information about pain management should be provided as part of prenatal education and the consent process must be carefully conducted to enhance women's autonomy. To fill in the significant gap in clinical knowledge about laboring women's decision-making capacity, well-designed prospective and retrospective studies may be required.

Clinical Research With Pregnant Women: Perspectives of Pregnant Women, Health Care Providers, and Researchers.

Limited clinical research with pregnant women has resulted in insufficient data to promote evidence-informed prenatal care. Charmaz's constructivist grounded theory methodology was used to explore how research with pregnant women would be determined ethically acceptable from the perspectives of pregnant women, health care providers, and researchers in reproductive sciences. Semistructured interviews were conducted with a purposive sample of 12 pregnant women, 10 health care providers, and nine reproductive science researchers. All three groups suggested the importance of informed consent and that permissible risk would be very limited and complex, being dependent on the personal benefits and risks of each particular study. Pregnant women, clinicians, and researchers shared concerns about the well-being of the woman and her fetus, and expressed a dilemma between promoting research for evidence-informed prenatal care while securing the safety in the course of research participation.

Implications of Applying Minimal Risk Standards in Clinical Research to Information Provision in Prenatal and Pre-conception Care.

BACKGROUND: There have long been minimal risk thresholds beneath which risks may not need to be discussed in clinical research. This threshold concept may be applied to clinical practice. Our research explored application of minimal risk standards in research regulations to providing information in prenatal and pre-conception care. METHODS: A case study approach applied minimal risk standards in research regulations to prenatal and pre-conception care with respect to the risks of excess alcohol consumption, folic acid insufficiency, exposure to phthalate plasticizers, and exposure to brominated flame retardants (BFRs). RESULTS: Excess alcohol consumption and folic acid insufficiency were found to be above the minimal risk standards as outlined in research regulations, while exposure to phthalates and BFRs requires more evidence to determine whether they are above minimal risk. However, applying the minimal risk standard based on the daily life of a healthy adult or a fetus in a healthy pregnant woman, phthalates and BFRs are at the minimal risk threshold regardless of their potential harm since all pregnant women may be exposed to these chemicals in their daily life. Nevertheless, if there is demonstration of sufficient evidence of harm, they may be above minimal risk if such harm can be reduced by individual choice to avoid exposure. CONCLUSION: The minimal risk concept in research regulations as applied to clinical practice may be useful to help clinicians and professional organizations determine what risks need be discussed in prenatal and pre-conception care.

Implications of the concept of minimal risk in research on informed choice in clinical practice.

The concept of a minimal risk threshold in research, beneath which exception to informed consent and ethics review processes may occur, has been codified for over 30 years in many national research regulations and by the Council for International Organizations of Medical Sciences. Although minimal risk in research constitutes one of the criteria for allowing waiver of informed consent or modification to the consent process and a large body of literature exists, discussion of a minimal risk threshold in clinical practice has not occurred. One reason for lack of discussion may be that implicit consent is accepted for a wide range of routine clinical practices. Extending the role of minimal risk in research to clinical practice might assist clinicians in identifying circumstances for which implicit consent is indeed sufficient and circumstances in which it is not. Further, concepts from minimal risk in research might assist clinicians regarding when information provision in health promotion is required. We begin by reviewing concepts in both minimal risk in research and informed choice in clinical practice. We then explore how a clinical minimal risk concept may clarify recommendations for information provision in clinical practice and support the patient's informed choice regarding therapeutic and diagnostic procedures and also health promotion. Given that clinical practice involves a broad scope of health information, professional practice guidelines on information provision based on the application of the minimal risk threshold in research could be developed to guide clinicians in what information must be provided to their patients.

Stereocontrolled syntheses of alpha-C-mannosyltryptophan and its analogues.

The total synthesis of alpha-C-mannosyltryptophan (C-Man-Trp), a naturally occurring C-glycosylamino acid, was achieved from a commercially available alpha-methyl-D-mannoside in 10 steps including the following key steps: the C-glycosidation of a mannose derivative with a stannylacetylene, Castro indole synthesis, and Sc(ClO4)3-promoted coupling with L-serine-derived aziridine carboxylate. The glucose- and galactose-analogues of C-Man-Trp were also synthesized in a similar manner. Conformational analyses of the synthesized C-glycosyltryptophan and its synthetic intermediate are briefly discussed.

Synthesis of novel alpha-C-glycosylamino acids and reverse regioselectivity in Larock's heteroannulation for the synthesis of the indole nucleus.

An alpha-C-iodoethynylglucose derivative was coupled with an L-serine-derived zinc-copper reagent to give alpha-C-glucosylpropargyl glycine, which underwent palladium catalyzed-heteroannulation with o-iodoaniline to give not alpha-C-glucosyl-tryptophan but alpha-C-glucosyl-iso-tryptophan. This is the first observation of complete reverse regioselectivity to Larock's proposal.