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1.
Anesth Analg ; 139(4): e38e-e39e, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39284147
2.
Vet Ophthalmol ; 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39072884

ABSTRACT

PURPOSE: To describe the clinical features surgical technique, early and long-term outcome with or without surgery, and histopathological findings of melanocytic anterior uveal lesions in young dogs. METHODS: Medical records of dogs at a guide dog facility removed from training due to a pigmented iris lesion were reviewed from 2014 to 2021. Selected dogs had surgical iridectomies performed. RESULTS: Iridal melanocytic lesions were characterized as well-delineated, pigmented, and flat (nevus) or raised (mass) lesions of the iris. Forty dogs (18 Labrador retrievers, 18 German shepherd dogs, 1 Golden retriever, 3 Labrador/Golden mixes) ranging from 0.5 to 3.1 years of age were affected unilaterally (n = 35) or bilaterally (n = 5). Sector iridectomy was performed in 13 dogs with prominent and well-isolated mass lesion and enucleation was carried out in 2 dogs with extensive lesions, while all other cases were monitored without surgical intervention. Postoperative complications included dyscoria (13/13), focal posterior synechia (9/13) and focal nonprogressive cataract (8/13). All eyes remained visual and comfortable up to 6.2 years post-iridectomy with no clinically identifiable local recurrence. Histopathology was consistent with uveal melanocytoma in all samples obtained surgically. All cases that did not undergo surgery remained free of complications up to 4.5 year post diagnosis. CONCLUSION: Melanocytic anterior uveal lesions may be overrepresented in certain lineages of breeds and be present at a young age. While none of the eyes developed complications when monitored without surgery, early surgical excision of the mass by sector iridectomy yields noteworthy functional outcome and retention of a comfortable globe.

3.
Adv Ther ; 41(6): 2500-2518, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38691316

ABSTRACT

INTRODUCTION: Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism. METHODS: PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m2. RESULTS: At week 52, over 95% (78/82) of participants remained enrolled in the OLE and of those, 86% maintained normocalcemia and 95% achieved independence from conventional therapy (no active vitamin D and ≤ 600 mg/day of calcium), with none requiring active vitamin D. Treatment with palopegteriparatide over 52 weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7) mL/min/1.73 m2 from baseline (P < 0.0001) and 43% of participants had an increase ≥ 10 mL/min/1.73 m2. In participants with baseline eGFR < 60 mL/min/1.73 m2, 52 weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73 m2 (P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide. CONCLUSION: In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week 52 in addition to previously reported maintenance and normalization of serum and urine biochemistries. Further investigation of palopegteriparatide for the preservation of renal function in hypoparathyroidism is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT04701203.


Chronic hypoparathyroidism is caused by inadequate parathyroid hormone (PTH) levels. Hypoparathyroidism is managed with conventional therapy (active vitamin D and calcium), but over time the disease itself and conventional therapy can increase the risk of medical complications including kidney problems. This study looked at how a new treatment for chronic hypoparathyroidism, palopegteriparatide (approved in the European Union under the brand name YORVIPATH®), affects kidney function in adults in the PaTHway clinical trial. Participants were randomly assigned to receive palopegteriparatide or a placebo injection once daily along with conventional therapy. For both groups, clinicians used a protocol to eliminate conventional therapy while maintaining normal blood calcium levels. After 26 weeks, participants on placebo switched to palopegteriparatide. Ninety-five percent of participants were still enrolled in the PaTHway trial after 52 weeks. Of those, 86% had normal blood calcium levels and 95% did not need conventional therapy (not taking vitamin D and not taking therapeutic doses of calcium [> 600 mg/day]). After 52 weeks of treatment with palopegteriparatide, significant improvements were seen in a measure of kidney function called estimated glomerular filtration rate (eGFR). Improvements in eGFR from the beginning of the trial to week 52 were considered clinically meaningful for over 57% of participants. In participants with impaired kidney function at the beginning of the trial, eGFR improvements were even greater, and 74% of participants had a clinically meaningful improvement. These results suggest that palopegteriparatide treatment may be beneficial for kidney function in adults with chronic hypoparathyroidism, especially those with impaired kidney function.


Subject(s)
Glomerular Filtration Rate , Hypoparathyroidism , Humans , Hypoparathyroidism/drug therapy , Male , Female , Middle Aged , Double-Blind Method , Glomerular Filtration Rate/drug effects , Adult , Parathyroid Hormone/blood , Parathyroid Hormone/therapeutic use , Aged , Chronic Disease , Vitamin D/therapeutic use , Treatment Outcome , Calcium/therapeutic use
4.
Fatigue ; 12(2): 101-122, 2024.
Article in English | MEDLINE | ID: mdl-38736736

ABSTRACT

Background: In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), post-exertional malaise (PEM) is associated with greater distress and symptoms. Cognitive Behavioral Stress Management (CBSM) has demonstrated beneficial effects for ME/CFS and may mitigate stress-related triggers of PEM. We tested a virtual CBSM intervention to increase access, and we report on its effects on stress and symptoms in ME/CFS patients with severe PEM. Methods: Data were from a randomized controlled trial (NCT01650636) comparing 10-week videoconference-delivered group CBSM (V-CBSM, n=75) to a 10-week Health Information active control (V-HI, n=75) in Fukuda criteria ME/CFS patients (71 classified as highPEM, 79 lowPEM). Linear regression explored PEM-by-Treatment interactions on overall symptom frequency and intensity, perceived stress, and fatigue-specific interference and intensity, at 5-month follow-up. Logistic regression tested V-CBSM effects on 5-month PEM status. Analyses controlled for age, gender, race/ethnicity, mode of symptom onset, and time since diagnosis. Results: The sample was middle-aged (47.96±10.89 years), mostly women (87%) and non-Hispanic White (65%), with no group differences on these variables or baseline PEM. For highPEM patients, V-CBSM (versus V-HI) demonstrated medium to large effects on follow-up symptom frequency, symptom intensity, fatigue interference, and fatigue intensity (p's < .05) and trending to significant reductions in perceived stress (p =.07). Differences were not evident for lowPEM patients. Treatment predicted follow-up PEM status at a trend (p = .058), with patients receiving V-CBSM demonstrating half the risk of highPEM classification versus V-HI. Conclusions: V-CBSM demonstrates benefits for ME/CFS patients presenting with severe PEM and may reduce the expression of PEM over time.

5.
Eur Neuropsychopharmacol ; 81: 28-37, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38310718

ABSTRACT

Schizophrenia and bipolar disorder exhibit substantial clinical overlap, particularly in individuals at familial high risk, who frequently present sub-threshold symptoms before the onset of illness. Severe mental disorders are highly polygenic traits, but their impact on the stages preceding the manifestation of mental disorders remains relatively unexplored. Our study aimed to examine the influence of polygenic risk scores (PRS) on sub-clinical outcomes over a 2-year period in youth at familial high risk for schizophrenia and bipolar disorder and controls. The sample included 222 children and adolescents, comprising offspring of parents with schizophrenia (n = 38), bipolar disorder (n = 80), and community controls (n = 104). We calculated PRS for psychiatric disorders, neuroticism and cognition using the PRS-CS method. Linear mixed-effects models were employed to investigate the association between PRS and cognition, symptom severity and functioning. Mediation analyses were conducted to explore whether clinical features acted as intermediaries in the impact of PRS on functioning outcomes. SZoff exhibited elevated PRS for schizophrenia. In the entire sample, PRS for depression, neuroticism, and cognitive traits showed associations with sub-clinical features. The effect of PRS for neuroticism and general intelligence on functioning outcomes were mediated by cognition and symptoms severity, respectively. This study delves into the interplay among genetics, the emergence of sub-clinical symptoms and functioning outcomes, providing novel evidence on mechanisms underpinning the continuum from sub-threshold features to the onset of mental disorders. The findings underscore the interplay of genetics, cognition, and clinical features, providing insights for personalized early interventions.


Subject(s)
Bipolar Disorder , Schizophrenia , Child , Humans , Adolescent , Genetic Risk Score , Genetic Predisposition to Disease/genetics , Bipolar Disorder/psychology , Schizophrenia/genetics , Schizophrenia/diagnosis , Cognition , Risk Factors
6.
Anesth Analg ; 138(2): 430-437, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37014966

ABSTRACT

BACKGROUND: The incidence of failed spinal anesthesia varies widely in the obstetric literature. Although many risk factors have been suggested, their relative predictive value is unknown. The primary objective of this retrospective cohort study was to determine the incidence of failed spinal anesthesia for cesarean deliveries at a tertiary care obstetric hospital, and its secondary objectives were to identify predictors of failed spinal anesthesia in the obstetrics population and quantify their relative importance in a predictive model for failure. METHODS: With local institutional ethics committee approval, a retrospective review of our hospital database identified the incidence of failed spinal anesthesia for 5361 cesarean deliveries between 2010 and 2019. We performed a multivariable analysis to assess the association of predictors with failure and a dominance analysis to assess the importance of each predictor. RESULTS: The incidence of failed spinal anesthesia requiring an alternative anesthetic was 2.1%, with conversion to general anesthesia occurring in 0.7% of surgeries. Supplemental analgesia or sedation was provided to an additional 2.0% of women. The most important predictors of a failed spinal anesthetic were previous cesarean delivery (odds ratio [OR], 11.33; 95% confidence interval [CI], 7.09-18.20; P < .001), concomitant tubal ligation (OR, 8.23; 95% CI, 3.12-19.20; P < .001), lower body mass index (BMI) (kg·m -2 , OR, 0.94; 95% CI, 0.90-0.98; P = .005), and longer surgery duration (minutes, OR, 1.02; 95% CI, 1.01-1.03; P = .006). Previous cesarean delivery was the most significant risk factor, contributing to 9.6% of the total 17% variance predicted by all predictors examined. CONCLUSIONS: Spinal anesthesia failed to provide a pain-free surgery in 4.1% of our cesarean deliveries. Previous cesarean delivery was the most important predictor of spinal failure. Other important predictors included tubal ligation, lower BMI, and longer surgery duration.


Subject(s)
Anesthesia, Obstetrical , Anesthesia, Spinal , Pregnancy , Female , Humans , Anesthetics, Local/adverse effects , Retrospective Studies , Anesthesia, Spinal/adverse effects , Incidence , Anesthesia, Obstetrical/adverse effects , Injections, Spinal/adverse effects
7.
Sci Rep ; 13(1): 19810, 2023 Nov 13.
Article in English | MEDLINE | ID: mdl-37957251

ABSTRACT

The enormous amount of data generated by sensors and other data sources in modern grid management systems requires new infrastructures, such as IoT (Internet of Things) and Big Data architectures. This, in combination with Data Mining techniques, allows the management and processing of all these heterogeneous massive data in order to discover new insights that can help to reduce the energy consumption of the building. In this paper, we describe a developed methodology for an Internet of Things (IoT) system based on a robust big data architecture. This innovative approach, combined with the power of Spark algorithms, has been proven to uncover rules representing hidden connections and patterns in the data extracted from a building in Bucharest. These uncovered patterns were essential for improving the building's energy efficiency.

8.
Transl Psychiatry ; 13(1): 155, 2023 05 08.
Article in English | MEDLINE | ID: mdl-37156786

ABSTRACT

Epigenetic modifications occur sequentially during the lifespan, but their pace can be altered by external stimuli. The onset of schizophrenia and bipolar disorder is critically modulated by stressors that may alter the epigenetic pattern, a putative signature marker of exposure to environmental risk factors. In this study, we estimated the age-related epigenetic modifications to assess the differences between young individuals at familial high risk (FHR) and controls and their association with environmental stressors. The sample included 117 individuals (6-17 years) at FHR (45%) and a control group (55%). Blood and saliva samples were used estimate the epigenetic age with six epigenetic clocks through methylation data. Environmental risk was measured with obstetric complications, socioeconomic statuses and recent stressful life events data. Epigenetic age was correlated with chronological age. FHR individuals showed epigenetic age deacceleration of Horvath and Hannum epigenetic clocks compared to controls. No effect of the environmental risk factors on the epigenetic age acceleration could be detected. Epigenetic age acceleration adjusted by cell counts showed that the FHR group was deaccelerated also with the PedBE epigenetic clock. Epigenetic age asynchronicities were found in the young at high risk, suggesting that offspring of affected parents follow a slower pace of biological aging than the control group. It still remains unclear which environmental stressors orchestrate the changes in the methylation pattern. Further studies are needed to better characterize the molecular impact of environmental stressors before illness onset, which could be critical in the development of tools for personalized psychiatry.


Subject(s)
Bipolar Disorder , Schizophrenia , Female , Pregnancy , Humans , Adolescent , DNA Methylation , Bipolar Disorder/genetics , Schizophrenia/genetics , Genetic Predisposition to Disease , Aging , Epigenesis, Genetic
9.
J Endocr Soc ; 7(5): bvad043, 2023 Mar 06.
Article in English | MEDLINE | ID: mdl-37091306

ABSTRACT

Context: Chronic hypoparathyroidism is conventionally treated with oral calcium and active vitamin D to reach and maintain targeted serum calcium and phosphorus levels, but some patients remain inadequately controlled. Objective: To assess long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment. Methods: This was an open-label extension study at 12 US centers. Adults (n = 49) with chronic hypoparathyroidism were included. The intervention was rhPTH(1-84) for 6 years. The main outcome measures were safety, biochemical measures, oral supplement doses, bone indices. Results: Thirty-eight patients (77.6%) completed the study. Throughout 72 months, mean albumin-adjusted serum calcium was within 2.00 to 2.25 mmol/L (8.0-9.0 mg/dL). At baseline, 65% of patients with measurements (n = 24/37) were hypercalciuric; of these, 54% (n = 13/24) were normocalciuric at month 72. Mean serum phosphorus declined from 1.6 ± 0.19 mmol/L at baseline (n = 49) to 1.3 ± 0.20 mmol/L at month 72 (n = 36). Mean estimated glomerular filtration rate was stable. rhPTH(1-84)-related adverse events were reported in 51.0% of patients (n = 25/49); all but 1 event were mild/moderate in severity. Mean oral calcium supplementation reduced by 45% ± 113.6% and calcitriol by 74% ± 39.3%. Bone turnover markers declined by month 32 to a plateau above pretreatment values; only aminoterminal propeptide of type 1 collagen remained outside the reference range. Mean bone mineral density z score fell at one-third radius and was stable at other sites. Conclusion: 6 years of rhPTH(1-84) treatment was associated with sustained improvements in biochemical parameters, a reduction in the percentage of patients with hypercalciuria, stable renal function, and decreased supplement requirements. rhPTH(1-84) was well tolerated; no new safety signals were identified.

11.
J Bone Miner Res ; 38(1): 14-25, 2023 01.
Article in English | MEDLINE | ID: mdl-36271471

ABSTRACT

Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once-daily TransCon PTH (initially 18 µg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF-36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Hypoparathyroidism , Parathyroid Hormone , Humans , Parathyroid Hormone/adverse effects , Calcium , Quality of Life , Vitamin D , Hormone Replacement Therapy/adverse effects , Calcium, Dietary , Minerals
13.
J Bone Miner Res ; 37(12): 2568-2585, 2022 12.
Article in English | MEDLINE | ID: mdl-36054621

ABSTRACT

This clinical practice guideline addresses the prevention, diagnosis, and management of hypoparathyroidism (HypoPT) and provides evidence-based recommendations. The HypoPT task forces included four teams with a total of 50 international experts including representatives from the sponsoring societies. A methodologist (GG) and his team supported the taskforces and conducted the systematic reviews. A formal process following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and the systematic reviews provided the structure for seven of the guideline recommendations. The task force used a less structured approach based on narrative reviews for 20 non-GRADEd recommendations. Clinicians may consider postsurgical HypoPT permanent if it persists for >12 months after surgery. To predict which patients will not develop permanent postsurgical HypoPT, we recommend evaluating serum PTH within 12 to 24 hours post total thyroidectomy (strong recommendation, moderate quality evidence). PTH > 10 pg/mL (1.05 pmol/L) virtually excludes long-term HypoPT. In individuals with nonsurgical HypoPT, genetic testing may be helpful in the presence of a positive family history of nonsurgical HypoPT, in the presence of syndromic features, or in individuals younger than 40 years. HypoPT can be associated with complications, including nephrocalcinosis, nephrolithiasis, renal insufficiency, cataracts, seizures, cardiac arrhythmias, ischemic heart disease, depression, and an increased risk of infection. Minimizing complications of HypoPT requires careful evaluation and close monitoring of laboratory indices. In patients with chronic HypoPT, the panel suggests conventional therapy with calcium and active vitamin D metabolites as first-line therapy (weak recommendation, low-quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers the use of PTH. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Hypoparathyroidism , Nephrocalcinosis , Humans , Hypoparathyroidism/drug therapy , Bone and Bones , Calcium, Dietary
14.
J Bone Miner Res ; 37(12): 2586-2601, 2022 12.
Article in English | MEDLINE | ID: mdl-36153665

ABSTRACT

The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. Given the pervasive nature of PTH deficiency across multiple organ systems, a detailed review of the skeletal, renal, neuromuscular, and ocular complications is provided. The burden of illness on affected patients and their caregivers contributes to reduced quality of life and social costs for this chronic endocrinopathy. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Hypoparathyroidism , Humans , Hypoparathyroidism/etiology , Hypoparathyroidism/physiopathology , Parathyroid Hormone/chemistry , Parathyroid Hormone/metabolism , Quality of Life , Parathyroid Glands/pathology , Parathyroid Glands/surgery
15.
Asia Pac J Oncol Nurs ; 9(9): 100085, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35935884

ABSTRACT

Objective: To assess the safety and efficacy of port-locking with heparin every 2 months vs. every 4 months and vs. saline solution every 2 months in patients with cancer not receiving active chemotherapy. The hypothesis stated that locking with heparin at four-month intervals and saline at two-month intervals would not increment > 10% of port obstructions. Methods: Multicentre, phase IV parallel, post-test control group study took place at the two chemotherapy units of oncology hospitals. Included patients with cancer with ports that completed the chemotherapy treatment but still having port maintenance care or blood samples taken up to four months. A sample of 126 patients with cancer in three arms was needed to detect a maximum difference of 10% for bioequivalence on the locking methods. Consecutive cases non-probabilistic sampling and randomized to one of the three groups; group A: received heparin 60 IU/mL every two months (control) vs. group B heparin every four months and vs. saline every two months in group C. Primary variables were the type of locking regimen, port obstruction, and absence of blood return, port-related infection, or venous thrombosis during the study period. Clinical and sociodemographic variables were also collected. Results: A total of 143 patients were randomly assigned; group A, 47 patients with heparin every 2 months, group B, 51 patients with heparin 4 months, and group C, 45 patients with saline every 2 months. All participants presented an adequate blood return and no obstructions, until the month of the 10th, when one participant in the group A receiving was withdrawn due to an absence of blood flow (P â€‹= â€‹0.587). Conclusions: Port locks with heparin every 4 months or saline every 2 months did not show differences in safety maintenance, infection, or thrombosis compared to heparin every 2 months.

16.
Bone Rep ; 17: 101596, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35734226

ABSTRACT

Fracture risk is increased in type 2 diabetes, which may in part be due to altered bone marrow adiposity. Cross sectional studies have reported that people with type 2 diabetes have lower unsaturated BMAT lipid levels than people without diabetes, although there are limited data on longitudinal changes. We hypothesized that Roux-en-Y gastric bypass (RYGB), which dramatically improves glycemic status, would have differential effects on BMAT composition, with increases in the unsaturated lipid index in people with diabetes. Given reports that axial BMAT is responsive to metabolic stimuli while appendicular BMAT is stable, we hypothesized that BMAT changes would occur at the spine but not the tibia. We enrolled 30 obese women, stratified by diabetes status, and used magnetic resonance spectroscopy to measure BMAT at the spine in all participants, and the tibia in a subset (n = 19). At baseline, BMAT parameters were similar between those with and without diabetes, except tibial marrow fat content was lower in women with diabetes (97.4 % ± 1.0 % versus 98.2 % ± 0.4 %, p = 0.04). Six months after surgery, both groups experienced similar weight loss of 27 kg ± 7 kg. At the spine, there was a significant interaction between diabetes status and changes in both marrow fat content and the unsaturated lipid index (p = 0.02, p < 0.01 for differences, respectively). Women with diabetes had a trend towards a decline in marrow fat content (-4.3 % ± 8.2 %, p = 0.09) and increase in the unsaturated lipid index (+1.1 % ± 1.5 %, p = 0.02). In contrast, BMAT parameters did not significantly change in women without diabetes. In all women, changes in the unsaturated lipid index inversely correlated with hemoglobin A1c changes (r = -0.47, p = 0.02). At the tibia, there was little BMAT change by diabetes status. Our results suggest that vertebral BMAT composition is responsive to changes in glycemic control after RYGB.

17.
PLoS Genet ; 18(3): e1010044, 2022 03.
Article in English | MEDLINE | ID: mdl-35271580

ABSTRACT

Congenital idiopathic megaesophagus (CIM) is a gastrointestinal (GI) motility disorder of dogs in which reduced peristaltic activity and dilation of the esophagus prevent the normal transport of food into the stomach. Affected puppies regurgitate meals and water, fail to thrive, and experience complications such as aspiration pneumonia that may necessitate euthanasia. The German shepherd dog (GSD) has the highest disease incidence, indicative of a genetic predisposition. Here, we discover that male GSDs are twice as likely to be affected as females and show that the sex bias is independent of body size. We propose that female endogenous factors (e.g., estrogen) are protective via their role in promoting relaxation of the sphincter between the esophagus and stomach, facilitating food passage. A genome-wide association study for CIM revealed an association on canine chromosome 12 (P-val = 3.12x10-13), with the lead SNPs located upstream or within Melanin-Concentrating Hormone Receptor 2 (MCHR2), a compelling positional candidate gene having a role in appetite, weight, and GI motility. Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk. Our findings suggest that the number of T-box protein binding motifs may correlate with MCHR2 expression and that an imbalance of melanin-concentrating hormone plays a role in CIM. We describe herein the first genetic factors identified in CIM: sex and a major locus on chromosome 12, which together predict disease state in the GSD with greater than 75% accuracy.


Subject(s)
Esophageal Achalasia , Minisatellite Repeats , Animals , Dogs , Esophageal Achalasia/veterinary , Female , Genome-Wide Association Study , Introns/genetics , Male , Receptors, Pituitary Hormone
18.
Semin Arthritis Rheum ; 53: 151972, 2022 04.
Article in English | MEDLINE | ID: mdl-35152085

ABSTRACT

OBJECTIVE: Prior studies have found conflicting results when evaluating the association between rheumatoid arthritis (RA) disease activity and bone mineral density (BMD). Whether or not cumulative RA disease activity is associated with BMD remains unanswered. METHODS: Data were from the University of California San Francisco RA Cohort from years 2006-2018. Those with BMD measures and at least two study visits prior to BMD measure were included in the study. The association between low cumulative disease activity, as measured by DAS28ESR, with the primary outcome of femoral neck BMD was assessed using multivariable linear regression. Sensitivity analyses were performed substituting CDAI for the disease activity measure as well as total hip and lumbar spine BMD as outcomes. RESULTS: 161 participants with RA were studied. The cohort was 62.4 ± 10.2 years old and 88% female. Hispanic/Latino (N = 73, 45%) and Asian (N = 59, 37%) were the most common racial/ethnic groups in our cohort. Mean RA duration was 10.5 ± 7.3 years and 83% were ACPA positive. Low disease activity was independently associated with higher femoral neck BMD compared to the moderate/high disease activity group (ß= 0.071 [95%CI: 0.021 to 0.122], p = 0.020). The relationship between low cumulative disease activity was similar when CDAI and other BMD sites were substituted in the multivariable models. CONCLUSION: Low cumulative disease activity as measured by DAS28ESR was associated with higher femoral neck BMD, independent of traditional osteoporosis risk factors (e.g., age, sex, BMI) in a unique RA cohort. Results were similar when evaluating cumulative low CDAI and other BMD sites.


Subject(s)
Arthritis, Rheumatoid , Osteoporosis , Absorptiometry, Photon , Aged , Arthritis, Rheumatoid/complications , Bone Density , Cohort Studies , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged
19.
Surg Infect (Larchmt) ; 23(1): 1-4, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34612706

ABSTRACT

Background: Surgical site infections (SSIs) continue to represent a substantial source of morbidity, mortality, and healthcare costs. The purpose of this study was to determine the effect of implementing a protocol using home pre-operative surgical preparation on the SSI rate at a large, urban safety-net medical center. Patients and Methods: From July through December 2020, Nose-to-Toes® (N2T; Sage Products-Stryker Corporation, Cary, IL) full-body preparation was applied by patients at home on the morning of scheduled surgical procedures. This study was a single-institution, retrospective observational analysis to determine the rates of SSI ≤30 days after an operation. Patients having skin preparation during 2020 (post-N2T) were compared with patients having the same operation during 2019 without having skin preparation (pre-N2T). Results: For gynecology, 10 (7.4%) of 135 pre-N2T and three (2.2%) of 135 post-N2T patients had SSIs. For surgical and gynecologic oncology, 13 (15.1%) of 86 pre-N2T and four (4.7%) of 86 post-N2T patients had SSIs. For orthopedics, four (4.3%) of 94 pre-N2T and zerp of 94 post-N2T patients had SSIs. Overall, 27 (8.6%) of 315 pre-N2T and seven (2.2%) of 315 post-N2T patients had SSIs (p = 0.0004). Conclusions: The implementation of pre-operative full-body preparation was associated with a substantial reduction in the incidence of SSI.


Subject(s)
Preoperative Care , Surgical Wound Infection , Female , Health Facilities , Humans , Incidence , Retrospective Studies , Risk Factors , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control
20.
J Vet Emerg Crit Care (San Antonio) ; 32(1): 106-112, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34699678

ABSTRACT

OBJECTIVE: To describe arrhythmias associated with administration of lidocaine in dogs treated for supraventricular tachyarrhythmias. CASE SUMMARIES: Four dogs with recent-onset supraventricular tachyarrhythmias: 3 dogs had atrial fibrillation (AF), and 1 had focal atrial tachycardia (FAT), which was thought to be AF at the time of assessment. The substrate of the supraventricular tachyarrhythmia was considered to be due to primary cardiomyopathy in 1 dog, high vagal tone in 2 dogs, and the change in hemodynamics from heavy sedation in 1 dog. Pharmacological cardioversion using lidocaine was only successful in the 2 dogs with vagally mediated AF. In these 2 cases, lidocaine administration resulted in a paroxysmal atrial flutter that was self-limiting and quickly led to sinus rhythm within 10 seconds in 1 dog but did not change over a 5-minute interval and required additional boluses in another dog. In the latter case, the dog showed severe bradycardia for 17.5 seconds prior to achieving sinus rhythm. The 2 unsuccessful cases both developed ventricular arrhythmias shortly after the lidocaine administration, with 1 case degenerating into ventricular fibrillation and cardiac arrest. NEW OR UNIQUE INFORMATION PROVIDED: Arrhythmias associated with lidocaine should be considered when treating dogs with supraventricular tachyarrhythmia.


Subject(s)
Atrial Fibrillation , Dog Diseases , Animals , Atrial Fibrillation/drug therapy , Atrial Fibrillation/veterinary , Dog Diseases/drug therapy , Dogs , Electric Countershock/veterinary , Lidocaine , Tachycardia/veterinary , Ventricular Fibrillation/veterinary
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