Alteration in the gut microbiome is associated with changes in bone metabolism after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6 mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1 N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P < .01) and femoral neck BMD decreased (mean -3.3%, P < .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (ß-diversity) postoperatively had greater increases in P1NP level (ρ = 0.48, P = .02) and greater bone loss at the femoral neck (ρ = -0.43, P = .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ = 0.56, P < .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ = 0.43, P = .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ = -0.43, P = .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, is a highly effective treatment for obesity because it produces dramatic weight loss and improves obesity-related medical conditions. However, it also results in abnormalities in bone metabolism. It is important to understand how LSG affects the skeleton, so that bone loss after surgery might be prevented. We studied adult men and women before and 6 mo after LSG, and we explored the relationship between the altered gut bacteria and bone metabolism changes. We found that: Those with greater shifts in their gut bacterial composition had more bone loss.Butyrate, a metabolite produced by gut bacteria from fermentation of dietary fiber, was associated with less bone breakdown and higher IGF-1 level (a bone-building hormone). We conclude that changes in the gut bacteria may contribute to the negative skeletal impact of LSG and reduced butyrate production by the gut bacteria leading to lower IGF-1 levels is a possible mechanism.

Intestinal Calcium Absorption Decreases After Laparoscopic Sleeve Gastrectomy Despite Optimization of Vitamin D Status.

CONTEXT: Laparoscopic sleeve gastrectomy (LSG), now the most commonly performed bariatric operation, is a highly effective treatment for obesity. While Roux-en-Y gastric bypass is known to impair intestinal fractional calcium absorption (FCA) and negatively affect bone metabolism, LSG's effects on calcium homeostasis and bone health have not been well characterized. OBJECTIVE: We determined the effect of LSG on FCA, while maintaining robust 25-hydroxyvitamin D (25OHD) levels and recommended calcium intake. DESIGN, SETTING, PARTICIPANTS: Prospective pre-post observational cohort study of 35 women and men with severe obesity undergoing LSG. MAIN OUTCOMES: FCA was measured preoperatively and 6 months postoperatively with a gold-standard dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and bone mineral density (BMD) by dual-energy X-ray absorptiometry and quantitative computed tomography. RESULTS: Mean ± SD FCA decreased from 31.4 ± 15.4% preoperatively to 16.1 ± 12.3% postoperatively (P < 0.01), while median (interquartile range) 25OHD levels were 39 (32-46) ng/mL and 36 (30-46) ng/mL, respectively. Concurrently, median 1,25-dihydroxyvitamin D level increased from 60 (50-82) pg/mL to 86 (72-107) pg/mL (P < 0.01), without significant changes in parathyroid hormone or 24-hour urinary calcium levels. Bone turnover marker levels increased substantially, and areal BMD decreased at the proximal femur. Those with lower postoperative FCA had greater areal BMD loss at the total hip (ρ = 0.45, P < 0.01). CONCLUSIONS: FCA decreases after LSG, with a concurrent rise in bone turnover marker levels and decline in BMD, despite robust 25OHD levels and with recommended calcium intake. Decline in FCA could contribute to negative skeletal effects following LSG.

Virtual Endocrinology Care Emphasizing Data-Driven Insights and Continuous Engagement and Its Impact on Glycemic Outcomes in Patients With Uncontrolled Diabetes: A Real-world Retrospective Case Series.

BACKGROUND: Steady Health's novel virtual care model incorporates continuous glucose monitoring (CGM) and a multidisciplinary approach to timely person-centered diabetes care. OBJECTIVE: This real-world retrospective case series explores the early glycemic outcomes of its patients with uncontrolled diabetes. METHODS: All patients of Steady Health who had an initial time in range (TIR) below 70% from their first 4 weeks of available CGM data and who had completed onboarding by February 2021 were included in this analysis. We compared the change in TIR, time below range, and average blood glucose from their first 4 weeks with their latest 4 weeks of available CGM data. Hemoglobin A1c (HbA1c) values at baseline and at the end of the study were also compared. Patients completed a questionnaire assessing their satisfaction with Steady Health's intervention. RESULTS: A total of 53 patients (n=35, 66% with type 1 diabetes; n=44, 83% treated with insulin) were included in this analysis. This cohort had a median baseline TIR of 53.0% (IQR 40.9%, 61.7%) and saw a median change in TIR of +16.6% (IQR +6.0%, +27.9%; P<.001) over a median duration of care of 11 months, amounting to nearly 4 more hours spent between 70 to 180 mg/dL a day. Of the 27 patients who had both baseline and follow-up HbA1c results, their median baseline HbA1c was 8.6% (IQR 7.5%, 11.4%; 70 mmol/mol), while their median change in HbA1c was -1.2% (IQR -2.6%, -0.2%; P=.001). Importantly, these glycemic improvements were achieved with a median decrease in the time below range by -0.3% (IQR -1.1%, 0.0%; P<.001), regardless of whether patients were started on an automated insulin delivery system. A total of 40 (75.5%) patients improved TIR by ≥5%, and 27 (50.9%) achieved TIR≥70% by the end of the study. Glycemic improvements were greatest among patients with the lowest baseline TIR and those who collaborated most intensively with Steady Health's clinicians. A total of 25 of these patients responded to a questionnaire assessing levels of satisfaction with their care, and all of them agreed that Steady Health had a positive impact on their diabetes management. CONCLUSIONS: Our findings suggest that patients with uncontrolled diabetes can achieve significant glycemic improvements by working with a virtual multidisciplinary care team that uses CGM to provide continuous clinical feedback and support.

Hyperlactatemia in diabetic ketoacidosis.

AIMS: The study examined the prevalence and degree of lactate elevation in diabetic ketoacidosis, and explored which biochemical abnormalities predicted L-lactate levels. METHODS: We reviewed episodes of diabetic ketoacidosis from 79 diabetes patients (one episode per patient). Separate univariate linear regression models were specified to predict lactate level from each of nine biochemical variables. Significant predictors from the univariate models were included in a final multivariate linear regression model to predict lactate levels. RESULTS: Mean (SD) lactate level was 3.05 (1.66) mmol/L; about 65% of patients had lactate levels >2 mmol/L. In the final multivariate linear regression model (R2  = 0.45), higher lactate levels were associated with greater hydrogen ion concentration (standardised ß = .60, t = 4.16, p < 0.0001), higher blood glucose (standardised ß = .28, t = 2.67, p = 0.009) and lower glomerular filtration rate estimated from creatinine (standardised ß = -.23, t = 2.29, p = 0.025). Bicarbonate, beta-hydroxybutyrate, body mass index, mean arterial pressure and calculated osmolality were not significant predictors of lactate level. There were three distinct patterns of lactate levels with treatment of diabetic ketoacidosis: group 1 = gradual decline, group 2 = initial increase and then decline and group 3 = initial decline followed by a transient peak and subsequent decline. CONCLUSIONS: Elevated lactate level is the norm in patients with diabetic ketoacidosis. Higher blood glucose levels and higher hydrogen ion concentrations are related to greater lactate. With treatment, there are different patterns of decline in lactate levels.

Prebiotic to Improve Calcium Absorption in Postmenopausal Women After Gastric Bypass: A Randomized Controlled Trial.

CONTEXT: The adverse skeletal effects of Roux-en-Y gastric bypass (RYGB) are partly caused by intestinal calcium absorption decline. Prebiotics, such as soluble corn fiber (SCF), augment colonic calcium absorption in healthy individuals. OBJECTIVE: We tested the effects of SCF on fractional calcium absorption (FCA), biochemical parameters, and the fecal microbiome in a post-RYGB population. METHODS: Randomized, double-blind, placebo-controlled trial of 20 postmenopausal women with history of RYGB a mean 5 years prior; a 2-month course of 20 g/day SCF or maltodextrin placebo was taken orally. The main outcome measure was between-group difference in absolute change in FCA (primary outcome) and was measured with a gold standard dual stable isotope method. Other measures included tolerability, adherence, serum calciotropic hormones and bone turnover markers, and fecal microbial composition via 16S rRNA gene sequencing. RESULTS: Mean FCA ± SD at baseline was low at 5.5 ± 5.1%. Comparing SCF to placebo, there was no between-group difference in mean (95% CI) change in FCA (+3.4 [-6.7, +13.6]%), nor in calciotropic hormones or bone turnover markers. The SCF group had a wider variation in FCA change than placebo (SD 13.4% vs 7.0%). Those with greater change in microbial composition following SCF treatment had greater increase in FCA (r2 = 0.72, P = 0.05). SCF adherence was high, and gastrointestinal symptoms were similar between groups. CONCLUSION: No between-group differences were observed in changes in FCA or calciotropic hormones, but wide CIs suggest a variable impact of SCF that may be due to the degree of gut microbiome alteration. Daily SCF consumption was well tolerated. Larger and longer-term studies are warranted.

FSH Level and Changes in Bone Mass and Body Composition in Older Women and Men.

CONTEXT: FSH may have independent actions on bone remodeling and body fat regulation. Cross-sectionally, we have shown that serum FSH is associated with bone mineral density (BMD) and body fat in older postmenopausal women, but it remains unknown whether FSH predicts bone and fat changes. OBJECTIVE: We examined whether baseline FSH level is associated with subsequent bone loss or body composition changes in older adults. SETTING, DESIGN, PARTICIPANTS: We studied 162 women and 158 men (mean age 82 ± 4 years) from the Age, Gene/Environment Susceptibility (AGES)-Bone Marrow Adiposity cohort, a substudy of the AGES-Reykjavik Study of community-dwelling older adults. Skeletal health and body composition were characterized at baseline and 3 years later. MAIN OUTCOMES: Annualized change in BMD and body composition by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Models were adjusted for serum estradiol and testosterone levels. RESULTS: There was no evidence for an association between baseline FSH level and change in BMD or body composition by DXA or QCT. For femoral neck areal BMD, adjusted mean difference (95% CI) per SD increase in FSH was 1.3 (-0.7 to 3.3) mg/cm2/y in women, and -0.2 (-2.6 to 2.2) mg/cm2/y in men. For visceral fat, adjusted mean difference (95% CI) per SD increase in FSH was 1.80 (-0.03 to 3.62) cm2/y in women, and -0.33 (-3.73 to 3.06) cm2/y in men. CONCLUSIONS: Although cross-sectional studies and studies in perimenopausal women have demonstrated associations between FSH and BMD and body composition, in older adults, FSH level is not associated with bone mass or body composition changes.

Ectopic Thyroid-Stimulating Hormone-Secreting Pituitary Adenoma of the Nasopharynx Diagnosed by Gallium 68 DOTATATE Positron Emission Tomography/Computed Tomography.

BACKGROUND: Ectopic thyroid-secreting hormone (TSH)-secreting pituitary adenomas are rare, with only 9 cases reported in the literature. CASE DESCRIPTION: We describe a case of an ectopic TSH-secreting pituitary adenoma located in the nasopharynx in a patient initially presenting with signs and symptoms of hyperthyroidism that persisted despite treatment with antithyroid medications. Magnetic resonance imaging of the pituitary gland was normal, although subsequent review by a neuroradiologist revealed a nodule attached to the posterior septum in the nasopharynx that was, in retrospect, seen on several other magnetic resonance imaging scans. Gallium 68 (68Ga) DOTATATE positron emission tomography/computed tomography showed increased uptake in the nasopharyngeal nodule. The patient underwent resection of the nasopharyngeal mass with remission of hyperthyroidism. On pathology, the resected mass stained positive for TSH and prolactin. CONCLUSIONS: This is the first report of use of 68Ga-DOTATATE positron emission tomography/computed tomography to aid in localizing an ectopic TSH-secreting tumor. Prior studies have shown that 68Ga-DOTATATE positron emission tomography/computed tomography improves detection of small lesions with shorter imaging times and lower radiation doses compared with other modalities. Our case emphasizes the importance of using 68Ga-DOTATATE PET/CT in the diagnosis of ectopic pituitary adenomas, as these tumors can be challenging to diagnose radiographically.

D-dimer as an applicable test for detection of posttraumatic deep vein thrombosis in lower limb fracture.

Measuring the plasma levels of D-dimer is an accurate and easy modality to detect deep vein thrombosis (DVT) in nontraumatic settings. However, the diagnostic reliability of D-dimer assays in detecting posttraumatic DVT among patients with lower limb fracture undergoing orthopedic surgery is not validated. In this study, 141 patients with lower limb fracture admitted through the emergency department and undergoing orthopedic surgery were enrolled. Postoperative venous blood samples for D-dimer assay were taken on the 1st, 7th, and 28th postoperative days. Color Doppler sonography examination of both lower limbs was performed at the same time as a standard test. Eight out of the 141 patients (6%) had acute DVT based on Color Doppler sonography. Mean D-dimer was 2160 ng/mL in DVT positive patients and 864 in DVT negative patients. D-dimer levels greater than 1000 ng/mL were 100% sensitive and 71% specific for detecting postoperative DVT. D-dimer assay is a useful and sensitive test for detecting posttraumatic DVT.

Radial stretch reveals distinct populations of mechanosensitive mammalian somatosensory neurons.

Primary afferent somatosensory neurons mediate our sense of touch in response to changes in ambient pressure. Molecules that detect and transduce thermal stimuli have been recently identified, but mechanisms underlying mechanosensation, particularly in vertebrate organisms, remain enigmatic. Traditionally, mechanically evoked responses in somatosensory neurons have been assessed one cell at a time by recording membrane currents in response to application of focal pressure, suction, or osmotic challenge. Here, we used radial stretch in combination with live-cell calcium imaging to gain a broad overview of mechanosensitive neuronal subpopulations. We found that different stretch intensities activate distinct subsets of sensory neurons as defined by size, molecular markers, or pharmacological attributes. In all subsets, stretch-evoked responses required extracellular calcium, indicating that mechanical force triggers calcium influx. This approach extends the repertoire of stimulus paradigms that can be used to examine mechanotransduction in mammalian sensory neurons, facilitating future physiological and pharmacological studies.