Impact of outpatient gastroenterology consult on pharmacotherapy and management of gastrointestinal symptoms in Parkinson's Disease.

Background & aims: Gastrointestinal (GI) symptoms are common in Parkinson's Disease (PD) patients, and GI dysmotility is thought to induce motor fluctuations, requiring escalation of levodopa therapy. The role of GI consultation in managing such symptoms, however, is unclear. In this study, we investigate the possible association between GI dysmotility symptoms and escalated LEDD therapy, as well as factors associated with GI consultation for PD symptom management. Methods: This was a retrospective case-study of 248 PD patients evaluated by outpatient neurology at Massachusetts General Brigham Healthcare from 2018 to 2022. Logistic regression, t-test, and Fisher exact tests were performed to identify factors associated with GI consult, change in LEDD with consult, and association of consultation with GI diagnoses and treatments, respectively. Results: Among 248 PD patients, 12.9% received GI consultation despite 96.8% having GI symptoms. Bloating was the primary symptom associated with receiving GI consultation (OR 3.59 [95% CI 1.47-8.88], p = 0.005). GI consultation increased the odds of receiving GI-specific medications (78.2% vs 46.3%, p = 0.001) and specialized GI diagnoses like gastroparesis (9.4% vs 0.46%, p < 0.001) and pelvic floor dysfunction (15.6% vs 0%, p < 0.0001). Interestingly, LEDD tended not to change after GI consultation, and dysmotility symptoms, including bloating, did not predict need for higher LEDD. Conclusions: While treating symptoms of dysmotility may not ameliorate levodopa-based motor fluctuations as much as previously thought, GI consultations are underutilized in PD, and patients who receive GI consultation are more likely to have changes in GI diagnosis and treatment.

Reflection Spectroscopy-Assessed Skin Carotenoids Are Sensitive to Change in Carotenoid Intake in a 6-Week Randomized Controlled Feeding Trial in a Racially/Ethnically Diverse Sample.

BACKGROUND: Reflection spectroscopy, utilized by the Veggie Meter, is a less-expensive, noninvasive method to quantify skin carotenoids and is a valid approximation of fruit and vegetable (FV) intake. However, it is unknown to what degree Veggie Meter-assessed skin carotenoid score change is responsive to changes in carotenoid intake. OBJECTIVES: This study aimed to evaluate Veggie Meter-assessed skin carotenoid score response in a 6-wk randomized controlled trial of a carotenoid-containing juice to determine whether the Veggie Meter can be used to detect nutritionally relevant changes in carotenoid intake; and to compare skin and plasma carotenoid responses with the 6-wk trial. METHODS: In this 6-wk trial, participants (n = 162) who self-identified as one of 4 US racial/ethnic groups (25% Black, 25% Asian, 27% non-Hispanic White, 23% Hispanic) were randomized to a control group, receiving negligible carotenoids (177 mL apple juice/d), moderate-dose group, receiving 4 mg total carotenoids/d (177 mL orange-carrot juice/d), or high-dose group, receiving 8 mg total carotenoids/d (355 mL orange-carrot juice/d). Skin carotenoid score and plasma total carotenoid concentrations (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein, zeaxanthin) were assessed at baseline, 3 wk, and 6 wk (n = 158 completed the trial). Repeated measures linear models were used to examine skin and plasma carotenoids over time and between groups. RESULTS: At 6 wk, participants in the high-dose and moderate-dose groups had significantly higher mean skin carotenoid scores [414.0 (SD = 100.6) and 369.7 (SD = 100.3), respectively] compared with those in the control group [305.2 (100.5)]. In the high-dose group, there was a 42% change in skin carotenoids from baseline (mean = 290.4) to a 6-wk follow-up (increase of 123, 123/290 = 42.4%). There was a 61% change in the plasma carotenoids in the high-dose group. CONCLUSIONS: The Veggie Meter is sensitive to increases in daily carotenoid intake in diverse racial/ethnic groups over 6 wk. CLINICAL TRIALS REGISTRY NUMBER: This trial was registered at clinicaltrials.gov as ID: NCT04056624. Study URL: https://clinicaltrials.gov/ct2/show/NCT04056624.

Noninvasive Reflection Spectroscopy Measurement of Skin Carotenoid Score in Infants Is Feasible and Reliable.

BACKGROUND: Skin carotenoid measurement by reflection spectroscopy (RS) offers a noninvasive biomarker of carotenoid intake, but feasibility, reliability, and validity are not established in infants. OBJECTIVES: In this study we aimed to determine the feasibility and reliability of 4-mo-old infant skin carotenoid score (SCS) measurement and its correlation with total carotenoid intake and plasma concentrations. METHODS: SCSs were measured in a prospective, observational study with a modified, portable RS device at the index finger and heel of the foot in 4-mo-olds (n = 21). Infant plasma, human milk, and formula carotenoid concentrations were measured by HPLC-photodiode array, and carotenoid intake was estimated from 7-d food diaries corrected for actual milk carotenoid content. Mean SCS, time to acquire measurements, replicate intraclass correlations, and bivariate correlations between SCS, carotenoid intake, and plasma carotenoids were examined. Exploratory analyses of returning 6- (n = 12) and 8-mo-old (n = 9) infants were conducted. RESULTS: Mean ± SD finger and heel SCSs in 4-, 6-, and 8-mo-olds were 92 ± 57 and 92 ± 51; 109 ± 41 and 119 ± 44; and 161 ± 89 and 197 ± 128 units, respectively. Replicate SCS measurements were reliable, with high intraclass correlation (≥0.70) of within-subject visit measurements. Finger SCSs in 4-mo-olds were correlated with carotenoid intake (ρ = 0.48, P = 0.0033), and finger and heel SCS were correlated with total plasma carotenoid concentrations (ρ = 0.71, P < 0.0001 and ρ = 0.57, P = 0.0006, respectively). Eight-mo-olds' finger and heel SCSs were correlated with total carotenoid intake (ρ = 0.73, P < 0.001; ρ = 0.58, P = 0.0014, respectively), whereas SCSs in 6-mo-olds, in transition from exclusive milk to complementary feeding, did not correlate with plasma carotenoid or dietary carotenoids, despite correlation between plasma and dietary carotenoid intake (ρ = 0.86, P = 0.0137). Mixed models suggest plasma total carotenoid concentration, age, carotenoid intake, and age × carotenoid intake, but not measurement site, are determinants of infant SCS. CONCLUSIONS: Infant skin carotenoids are feasibly and reliably measured by RS and may provide a biomarker of carotenoid intake in 4-mo-olds. This trial was registered at clinicaltrials.gov as NCT03996395.

Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations.

Craniosynostosis, the premature fusion of one or more cranial sutures, affects 1 in 2,500 live births. Isolated single-suture fusion is most prevalent, with sagittal synostosis occurring in 1/5,000 live births. The etiology of isolated (nonsyndromic) single-suture craniosynostosis is largely unknown. In syndromic craniosynostosis, there is a highly nonrandom pattern of causative autosomal dominant mutations involving TWIST1 and fibroblast growth factor receptors (FGFRs). Prior to our study, there were no published TWIST1 mutations in the anti-osteogenic C-terminus, recently coined the TWIST Box, which binds and inhibits RUNX2 transactivation. RUNX2 is the principal master switch for osteogenesis. We performed mutational analysis on 164 infants with isolated, single-suture craniosynostosis for mutations in TWIST1, the IgIIIa exon of FGFR1, the IgIIIa and IgIIIc exons of FGFR2, and the Pro250Arg site of FGFR3. We identified two patients with novel TWIST Box mutations: one with isolated sagittal synostosis and one with isolated coronal synostosis. Kress et al. [2006] reported a TWIST Box "nondisease-causing polymorphism" in a patient with isolated sagittal synostosis. However, compelling evidence suggests that their and our sequence alterations are pathogenic: (1) a mouse with a mutation of the same residue as our sagittal synostosis patient developed sagittal synostosis, (2) mutation of the same residue precluded TWIST1 interaction with RUNX2, (3) each mutation involved nonconservative amino acid substitutions in highly conserved residues across species, and (4) control chromosomes lacked TWIST Box sequence alterations. We suggest that genetic testing of patients with isolated sagittal or coronal synostosis should include TWIST1 mutational analysis.