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Introduction: Insulinomas are rare, usually sporadic, and typically benign pancreatic neuroendocrine tumours. Pre-operative localization is challenging and evidence on comparative analysis of anatomic and scintigraphic modalities for pre-operative tumour localization is limited, even in contemporary series. Methods: The current study was designed to study the clinical features and management challenges of insulinomas managed at a tertiary care centre. Clinical features, diagnosis, imaging techniques, surgical procedures, and outcomes details were collated. Pre-operative imaging techniques (CT/MRI, nuclear scintigraphy) were compared with intraoperative and histopathological findings to assess their accuracy of localization. Results: Thirty-seven patients (15 females [42%]; median age 36 years [IQR 28-49]) were included in the study. In four patients (10.8%), the tumour occurred in the setting of multiple endocrine neoplasia type 1 (MEN 1) while the remaining were sporadic. The sensitivity of pre-operative localization was 61.5% (multiphasic CT), 66.6% (multiphasic MRI), 100% (68Ga Exendin-4 PET-CT), and 91.6% (EUS). Three patients with normal multiphasic CT had localization on 68Ga Exendin-4 PET-CT. The positive predictive value (PPV) of both Exendin-PET-CT and EUS was similar at 91.6% and 91.6%, respectively. All patients (except one with nesidioblastosis), who underwent enucleation or partial pancreatic resection, were cured. Conclusion: 68Ga Exendin-4 PET-CT based is a non-invasive imaging modality that has high sensitivity and PPV and can be used as a first-line imaging modality. The overall prognosis of these tumours is good with high cure rates attained following surgical resection.
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INTRODUCTION: Charcot neuro-osteoarthropathy (CNO) occurs late in diabetes and may cause fracture, deformity, and higher mortality. Diabetic kidney disease (DKD) affects bone metabolism and contributes to mortality. However, there is no data on prevalence of CNO and its outcomes with coexisting DKD (or chronic kidney disease [CKD]). METHODS: To ascertain the prevalence of CKD (pick CKD or DKD) among patients with CNO and delineate the remission of active CNO and subsequent lower extremity amputation and all-cause mortality during prospective follow-up. Consecutive patients with diabetic CNO (active or inactive) were enrolled and subsequently divided into those with and without CKD (pick CKD or DKD) (Group A and Group B, respectively). A preestablished timeframe of 36 weeks was utilized to evaluate the remission proportion of active CNO. RESULTS: A total of 493 CNO patients were observed and 449 subjects (150 patients had active CNO) were further evaluated. The overall prevalence of diabetic nephropathy (DKD or CKD?) CNO was 43.7%. The proportion of patients achieving remission was significantly lower in Group A compared to Group B (OR 0.468, CI [0.239-0.934], P = .025), however, the median time for achieving remission was similar between the 2 groups (14 weeks vs 16 weeks, P = .885). Overall, all-cause mortality was notably higher Group A compared to Group B (OR 2.23, 95% CI [1.474-3.368]) over a median follow-up of 4 years. No significant differences were observed in rates of diabetic foot ulcers (58.2% vs 54.9%; P = .584) and amputations (17.4% vs 15.12%; P = .889) between Group A and Group B. CONCLUSION: Patients of CNO with coexisting CKD have poor prognosis both in terms of likelihood of active CNO remission and higher mortality.
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Sjogren's syndrome is a known cause of renal tubular acidosis (RTA). However, osteomalacia associated with Sjogren's syndrome is rare and seldom reported in literature. We report a case of pseudofractures of both femora due to osteomalacia as a result of RTA secondary to Sjogren's syndrome, which was initially misdiagnosed as a stress fracture. A man in his 30s presented with hip pain and was initially misdiagnosed to have stress fractures because of the 'through and through' extension of the 'fracture' lines at the neck of both femora. The patient had a normal serum biochemistry profile except for elevated alkaline phosphatase levels. On further evaluation, he was found to have distal RTA secondary to Sjogren's syndrome. The patient responded to sodium bicarbonate therapy with clinical, biochemical and radiological improvement. A high index of suspicion for RTA should be kept in a patient with osteomalacia with a normal calcium profile and vitamin D level.
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Osteomalacia , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Masculino , Osteomalacia/etiología , Osteomalacia/diagnóstico , Adulto , Acidosis Tubular Renal/diagnóstico , Acidosis Tubular Renal/etiología , Acidosis Tubular Renal/complicaciones , Diagnóstico Diferencial , Fracturas por Estrés/etiología , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/diagnóstico , Bicarbonato de Sodio/uso terapéuticoRESUMEN
The compatibility of bone graft substitutes (BGS) with mesenchymal stem cells (MSCs) is an important parameter to consider for their use in repairing bone defects as it eventually affects the clinical outcome. In the present study, a few commercially available BGS - ß-tricalcium phosphate (ß-TCP), calcium sulfate, gelatin sponge, and different forms of hydroxyapatite (HAP) were screened for their interactions with MSCs from adipose tissue (ADSCs). It was demonstrated that HAP block favorably supported ADSC viability, morphology, migration, and differentiation compared to other scaffolds. The results strongly suggest the importance of preclinical evaluation of bone scaffolds for their cellular compatibility. Furthermore, the bone regenerative potential of HAP block with ADSCs was evaluated in an ex vivo bone defect model developed using patient derived trabecular bone explants. The explants were cultured for 45 days in vitro and bone formation was assessed by expression of osteogenic genes, ALP secretion, and high resolution computed tomography. Our findings confirmed active bone repair process in ex vivo settings. Addition of ADSCs significantly accelerated the repair process and improved bone microarchitecture. This ex vivo bone defect model can emerge as a viable alternative to animal experimentation and also as a potent tool to evaluate patient specific bone therapeutics under controlled conditions.
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Tejido Adiposo , Regeneración Ósea , Diferenciación Celular , Células Madre Mesenquimatosas , Ingeniería de Tejidos , Andamios del Tejido , Humanos , Tejido Adiposo/citología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Células Madre Mesenquimatosas/citología , Cabeza Femoral , Osteogénesis , Células Cultivadas , Sustitutos de Huesos/química , Durapatita/química , Fosfatos de Calcio/químicaRESUMEN
This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also exhibited hyposmia, eunuchoid stature and gynecomastia. Biochemical investigations revealed low levels of testosterone, luteinising hormone and follicle-stimulating hormone. Hence, he was diagnosed with Kallmann syndrome. Imaging studies showed an absent right kidney and cystic dilatation of the distal ureteric bud, seminal vesicle and absent/hypoplastic ejaculatory duct. The association of hypogonadotropic hypogonadism with Zinner syndrome, a rare condition characterised by renal agenesis, seminal vesicle cyst and ejaculatory duct obstruction, was noted.
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Hipogonadismo , Síndrome de Kallmann , Humanos , Masculino , Hipogonadismo/complicaciones , Hipogonadismo/diagnóstico , Síndrome de Kallmann/complicaciones , Síndrome de Kallmann/diagnóstico , Vesículas Seminales/anomalías , Vesículas Seminales/diagnóstico por imagen , Riñón/anomalías , Conductos Eyaculadores/anomalías , Conductos Eyaculadores/diagnóstico por imagen , Adulto , Pene/anomalíasRESUMEN
BACKGROUND: Serum IGF-1 is an important biochemical tool to diagnose and monitor GH-related disorders. However, ethnic-specific Indian data following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage-specific normative data for IGF-1 in healthy Indian children and adolescents. METHODS: A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. RESULTS: We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7â ng/mL), BA of 14 years (350.2â ng/mL) and Tanner stage IV (345â ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9â ng/mL) BA of 15 years (340.6â ng/mL) and Tanner stage III (304.8â ng/mL). Girls had earlier rise, peak and higher IGF-1 values. The reference interval (2.5th-97.5th percentile) was broader during peri-pubertal ages, indicating a higher physiological variability. CONCLUSION: This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents.
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Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.
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Disponibilidad Biológica , Cissus , Sistemas de Liberación de Medicamentos , Emulsiones , Osteoporosis , Animales , Osteoporosis/tratamiento farmacológico , Ratas , Cissus/química , Sistemas de Liberación de Medicamentos/métodos , Femenino , Administración Oral , Excipientes/química , Solubilidad , Extractos Vegetales/farmacocinética , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Tamaño de la Partícula , Ratas Sprague-DawleyRESUMEN
Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.
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BACKGROUND AND AIMS: Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (1H NMR). MATERIALS AND METHODS: Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using 1H NMR spectroscopy. RESULTS: Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker. CONCLUSION: The 1H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.
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Biomarcadores , Diabetes Mellitus Tipo 2 , Metabolómica , Osteoporosis Posmenopáusica , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Metabolómica/métodos , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico , Anciano , Espectroscopía de Resonancia Magnética/métodos , MetabolomaRESUMEN
Adrenal adenomas/incidentalomas with mild autonomous cortisol secretion (MACS)/subclinical hypercortisolism (SH) are often associated with metabolic syndrome, glucocorticoid-induced osteoporosis, and fractures. In this background, the present systematic review and meta-analysis aimed to collate the available evidence and provide a summary of the effect of MACS/SH on bone health in terms of fractures, osteoporosis/osteopenia, microarchitecture, and bone turnover. PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched for observational studies reporting prevalence of fractures, osteoporosis/osteopenia or data on bone microarchitecture/bone turnover markers (BTMs). Following literature search, 16 observational studies were included. Pooled prevalence of any fractures (vertebral and non-vertebral), vertebral fractures, and osteoporosis/osteopenia in MACS/SH were 43% [95% confidence intervals (CI): 23%, 62%], 45% (95% CI: 22%, 68%) and 50% (95% CI: 33%, 66%), respectively. On meta-regression, age, sex, 24-hour urinary free cortisol, and dehydroepiandrosterone-sulfate did not predict fracture risk. The likelihood of any fractures [odds ratio (OR) 1.61; 95% CI: 1.18, 2.20; P = 0.0026], vertebral fractures (OR 2.10; 95% CI: 1.28, 3.45; P = 0.0035), and osteoporosis/osteopenia (OR 1.46; 95% CI: 1.15, 1.85; P = 0.0018) was significantly higher in adrenal adenomas and MACS/SH than non-functional adrenal adenomas. Subjects with MACS/SH had significantly lower bone mineral density (BMD) at lumbar spine [mean difference (MD) -0.07 g/cm2; 95% CI: -0.11, -0.03; P = 0.0004) and femoral neck (MD -0.05 g/cm2; 95% CI: -0.08, -0.02; P = 0.0045) than their non-functional counterparts. Limited data showed no significant difference in BTMs. Publication bias was observed in the pooled prevalence of any fractures, vertebral fractures and pooled MD of femoral neck BMD. To conclude, people with adrenal adenomas/incidentalomas and MACS/SH are at a 1.5- to 2-fold higher likelihood of fractures and osteoporosis/osteopenia compared to non-functional adrenal adenomas and should routinely be screened for bone disease. Nevertheless, considering the modest sample size of studies and evidence of publication bias, larger and high-quality studies are required (CRD42023471045).
Mild autonomous cortisol secretion (MACS), often also referred to as subclinical hypercortisolism (SH), is usually associated with an underlying adrenal incidentaloma (AI), an adrenal mass incidentally found during abdomen imaging. Although signs of overt cortisol excess are lacking, subjects with MACS/SH often have features of metabolic syndrome, osteoporosis and fractures. The present systematic review and meta-analysis showed that the pooled prevalence of any fractures (vertebral and nonvertebral), vertebral fractures, and osteoporosis/osteopenia in MACS/SH were 43%, 45%, and 50%, respectively. People with adrenal adenomas/incidentalomas and MACS/SH are at a 1.5- to 2-fold higher likelihood of fractures and osteoporosis/osteopenia compared to nonfunctional adrenal adenomas. Besides, subjects with MACS/SH had significantly lower bone mineral density at lumbar spine and femoral neck than their nonfunctional counterparts. It is thus imperative to assess bone health in all subjects with MACS/SH.
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Neoplasias de las Glándulas Suprarrenales , Síndrome de Cushing , Fracturas Óseas , Hidrocortisona , Humanos , Hidrocortisona/metabolismo , Síndrome de Cushing/complicaciones , Síndrome de Cushing/metabolismo , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/metabolismo , Fracturas Óseas/epidemiología , Fracturas Óseas/metabolismo , Factores de Riesgo , Huesos/metabolismo , Huesos/patología , Adenoma/metabolismo , Adenoma/complicaciones , Adenoma/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B in differentiating premature thelarche from gonadotropin-dependent precocious puberty (GDPP). METHODS: This was a prospective interventional study. Basal and FSH-stimulated inhibin B levels were estimated in girls presenting with thelarche < 8 years age (n = 10), healthy girls with normal pubertal development (pubertal control) (n = 8) and healthy prepubertal girls (prepubertal control) (n = 7). Girls with early puberty were classified as premature thelarche or GDPP based on GnRH agonist stimulation test. RESULTS: Median (IQR) basal inhibin B levels (pg/mL) in premature thelarche was 5.42 (2.91, 30.58) and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) (P = 0.043). Median (IQR) basal inhibin B in GDPP was 64.11 (24.96, 792.45) pg/mL and FSH-stimulated inhibin B was 833.66 (500.11-1266.18) pg/mL (P = 0.043). Basal inhibin B was discriminatory between GDPP and premature thelarche (P = 0.032). Median (IQR) basal inhibin B in prepubertal and pubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively. CONCLUSION: Basal inhibin B is useful in differentiation of premature thelarche from GDPP while the role of FSH-stimulated inhibin B needs to be further explored in large sample size.
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Hormona Folículo Estimulante , Inhibinas , Pubertad Precoz , Niño , Preescolar , Femenino , Humanos , Hormona Folículo Estimulante/sangre , Inhibinas/sangre , Estudios Prospectivos , Pubertad Precoz/sangreRESUMEN
AIMS: The use of Continuous Glucose Monitoring System (CGMS) improves glycemic parameters in Type 1 Diabetes Mellitus (T1D), but the cost is prohibitive. Here, we investigated the effect of short-term application of real-time and intermittently-scanned CGMS (rt and is-CGMS) in T1D individuals on change in HbA1c at the end of 3 months. METHODS: T1D individuals were randomized into three groups in a ratio of 1:1:2 - Group A (rt-CGMS for 2 weeks initially, followed by is-CGMS for 2 weeks at 3 months), Group B (is-CGMS for 2 weeks initially followed by rt-CGMS for 2 weeks at 3 months) and Group C (only self-monitoring of blood glucose), respectively. HbA1c at baseline, 3, and 6 months were compared. RESULTS: Out of a total 68 T1D patients, HbA1c decreased significantly in groups A and B at 6 months compared to the baseline, but not in group C. HbA1c was significantly lower in Group A compared to Group C at 3 and 6 months. Fructosamine levels significantly decreased in Group B before and after cross-over. Glycemic variability indices improved significantly after cross-over from is-CGMS to rt-CGMS. CONCLUSION: Intermittent application of CGMS for 2 weeks improves short- and long-term blood glucose control in T1D.
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Diabetes Mellitus Tipo 1 , Adulto , Humanos , Adolescente , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucemia , Hemoglobina Glucada , Estudios Cruzados , Automonitorización de la Glucosa Sanguínea , Monitoreo Continuo de GlucosaRESUMEN
Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.
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Enfermedades Óseas Metabólicas , Hipopituitarismo , Osteoporosis , Femenino , Humanos , Adulto , Persona de Mediana Edad , Densidad Ósea , Osteoporosis/diagnóstico por imagen , Hipopituitarismo/diagnóstico por imagen , Hipopituitarismo/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Tibia/diagnóstico por imagen , Radio (Anatomía) , Absorciometría de Fotón/métodosRESUMEN
AIM: This study was undertaken to explicate the shared and distinctive genetic susceptibility and immune dysfunction in patients with T1D alone and T1D with CD (T1D + CD). METHODS: A total of 100 T1D, 50 T1D + CD and 150 healthy controls were recruited. HLA-DRB1/DQB1 alleles were determined by PCR-sequence-specific primer method, SNP genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP-array and genotyping for INS-23 Hph1 A/T was done by RFLP. Autoantibodies and cytokine estimation was done by ELISA. Immune-regulation was analysed by flow-cytometry. Clustering of autoantigen epitopes was done by epitope cluster analytical tool. RESULTS: Both T1D alone and T1D + CD had a shared association of DRB1*03:01, DRB1*04, DRB3*01:07/15 and DQB1*02. DRB3*01:07/15 confers the highest risk for T1D with relative risk of 11.32 (5.74-22.31). Non-HLA gene polymorphisms PTPN22 and INS could discriminate between T1D and T1D + CD. T1D + CD have significantly higher titers of autoantibodies, expression of costimulatory molecules on CD4 and CD8 cells, and cytokine IL-17A and TGF-ß1 levels compared to T1D patients. Epitopes from immunodominant regions of autoantigens of T1D and CD clustered together with 40% homology. CONCLUSION: Same HLA genes provide susceptibility for both T1D and CD. Non-HLA genes CTLA4, PTPN22 and INS provide further susceptibility while different polymorphisms in PTPN22 and INS can discriminate between T1D and T1D + CD. Epitope homology between autoantigens of two diseases further encourages the two diseases to occur together. The T1D + CD being more common in females along with co-existence of thyroid autoimmunity, and have more immune dysregulated state than T1D alone.
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Autoantígenos , Enfermedad Celíaca , Diabetes Mellitus Tipo 1 , Predisposición Genética a la Enfermedad , Proteína Tirosina Fosfatasa no Receptora Tipo 22 , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , India/epidemiología , Enfermedad Celíaca/genética , Enfermedad Celíaca/inmunología , Femenino , Masculino , Autoantígenos/inmunología , Autoantígenos/genética , Niño , Adolescente , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Adulto , Cadenas beta de HLA-DQ/genética , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Cadenas HLA-DRB1/genética , Adulto Joven , Polimorfismo de Nucleótido Simple , Preescolar , Antígeno CTLA-4/genética , Genotipo , Estudios de Casos y ControlesRESUMEN
ABSTRACT: Peptide receptor radionuclide therapy (PRRT) has shown to be effective and safe in metastatic gastroenteropancreatic and nongastroenteropancreatic neuroendocrine tumors. However, the selection criteria for PRRT are restricted to patients with good performance status (Eastern Cooperative Oncology Group score ≤2 or Karnofsky performance score ≥60). This denies many patients with adequate somatostatin receptor expression and biochemical profiles from the beneficial effects of PRRT on the quality of life, daily function, and overall survival. The 2 cases highlight the favorable response of PRRT in patients with metastatic neuroendocrine tumor having a very poor performance status initially.
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Tumores Neuroendocrinos , Octreótido , Compuestos Organometálicos , Terapia Recuperativa , Humanos , Progresión de la Enfermedad , Tumores Neuroendocrinos/radioterapia , Tumores Neuroendocrinos/diagnóstico por imagen , Octreótido/análogos & derivados , Octreótido/uso terapéutico , Compuestos Organometálicos/uso terapéuticoRESUMEN
INTRODUCTION: Patients with ulcerative colitis (UC) are likely to have poor nutritional intake and increased gut losses. This study was designed to study the prevalence and predictors of nutritional deficiencies in patients with UC and their impact on the quality of life (QOL). METHODS: A prospective study was conducted among consenting patients with UC (cases) and healthy relatives of the cases (controls) visiting a university teaching hospital. They were assessed for clinical, demographic, endoscopic (Mayo score) and histological profile (Robart's score). They were assessed for the presence of macronutrient and micronutrient deficiency, anthropometry, functional status (muscle strength by dynamometer and sit-to-stand test) and the quality of life (short inflammatory bowel disease questionnaire [SIBDQ]). A SIBDQ score of ≤ 50 was considered poor QOL. RESULTS: We studied 126 cases and 57 healthy controls (age [mean ± SD] 37.7 ± 13.2 years vs. 34.40 ± 11.05 years; [p = 0.10] females [38.1% vs. 38.7%]; p = 0.94). Cases more often were underweight (28% vs. 3.5%; p < 0.001), had low mid arm circumference (45% vs. 12%; p < 0.0001), lower functional status in the form of weaker hand grip strength (67% vs. 45.6%; p = 0.007) and weaker lower limb strength (80% vs. 42%; p < 0.0001). Cases more often had the evidence of macronutrient deficiencies: total serum protein deficiency (31% vs. 3.5%; p < 0.0001), serum albumin deficiency (25.4% vs. 0.00%; p < 0.0001) and cholesterol deficiency (63% vs. 28%; p < 0.0001). Micronutrient deficiencies were highly prevalent among cases: calcium (44%), phosphate (21%), magnesium (11%), zinc (76%), iron (87%), folate (16%), vitamin B12 (10%) and vitamin D (81%). Most cases had a poor quality of life (85/126; 67.5%). Factors associated with poor QOL were low hemoglobin, serum albumin, zinc and vitamin D levels and histologically active disease. On multi-variate analysis, low vitamin D levels (odds ratio [OR] = 6.1; 95% confidence interval [CI]: 1.9-19.7) and histologically active disease (OR = 4.0; 95% CI: 1.6-9.9) were identified as independent predictors of poor QOL. CONCLUSIONS: Macronutrient deficiency, micronutrient deficiency, lower functional status and poorer QOL are highly prevalent among patients with UC. The independent predictors of poor QOL were histologically active disease and low serum vitamin D levels. Identifying and correcting the deficiencies may help in improving the QOL of patients with UC.
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Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/complicaciones , Calidad de Vida , Estudios Prospectivos , Estado Funcional , Fuerza de la Mano , Vitamina D , Enfermedades Inflamatorias del Intestino/complicaciones , Vitaminas , Zinc , Albúmina SéricaRESUMEN
BACKGROUND: Strain echocardiography is a highly sensitive modality for detecting myocardial disease at an early stage. Therefore, we aim to evaluate subclinical left ventricular dysfunction in primary hyperparathyroidism (PHPT) patients with myocardial strain imaging in addition to conventional echocardiography and to look for its reversal after parathyroidectomy (PTx). METHODS: Thirty patients who underwent curative parathyroidectomy for PHPT were included. All patients were evaluated with M mode echo, 2D echo and strain imaging before and 6 months after PTx. Left ventricular ejection fraction, left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH), Global Longitudinal Strain (GLS) and global circumferential strain (GCS) were recorded. RESULTS: On M mode echo, LVH was present in 15 patients and 8 of them improved completely after PTx (p < 0.038). Incidence of systolic and diastolic dysfunction on 2D echo was 10% and 13.3% respectively; while myocardial strain imaging showed impaired systolic function in 46.7% patients. Hence, compared to conventional 2D echo, strain imaging showed 36.7% high detection rate of subnormal cardiac function. There was improvement in left ventricle dysfunction (p = 0.083), GLS and GCS (p = 0.034) after PTx. Serum parathormone demonstrated a strong positive correlation with change in GLS and GCS (p = 0.013, p = 0.126) while serum calcium showed a weak correlation with change in GLS and GCS following surgery. CONCLUSION: Myocardial strain imaging should be considered for all PHPT patients as early identification of subclinical ventricle dysfunction provides an opportunity for an early intervention and thereby preventing development of irreversible LV dysfunction.
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Ecocardiografía , Hiperparatiroidismo Primario , Paratiroidectomía , Disfunción Ventricular Izquierda , Humanos , Hiperparatiroidismo Primario/cirugía , Hiperparatiroidismo Primario/diagnóstico por imagen , Hiperparatiroidismo Primario/complicaciones , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Ecocardiografía/métodos , Adulto , Anciano , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Association of sarcopenia with disease severity in ulcerative colitis (UC) is not clearly defined. We planned to estimate the prevalence of sarcopenia in patients with UC as per the revised definition and its relation with the disease severity. METHODS: A cross-sectional assessment of sarcopenia in patients with UC was performed. Disease activity was graded according to complete Mayo score. Hand grip strength was assessed with Jamar hand dynamometer, muscle mass using a dual energy X-ray absorptiometry scan, and physical performance with 4-m walk test. Sarcopenia was defined as a reduction of both muscle mass and strength. Severe sarcopenia was defined as reduced gait speed in presence of sarcopenia. RESULTS: Of 114 patients (62 males, mean age: 36.49±12.41 years), 32 (28%) were in remission, 46 (40.4%) had mild-moderate activity, and 36 (31.6%) had severe UC. Forty-three patients (37.7%) had probable sarcopenia, 25 (21.9%) had sarcopenia, and 14 (12.2%) had severe sarcopenia. Prevalence of sarcopenia was higher in active disease (2 in remission, 6 in active, and 17 in severe, P<0.001). Of 14 with severe sarcopenia, 13 had severe UC while 1 had moderate UC. On multivariate analysis, lower body mass index and higher Mayo score were associated with sarcopenia. Of 37 patients with acute severe colitis, 16 had sarcopenia. Requirement of second-line therapy was similar between patients with and without sarcopenia. On follow-up (median: 18 months), there was a non-significant higher rate of major adverse events in those with sarcopenia (47.4% vs. 33.8%, P=0.273). CONCLUSIONS: Sarcopenia and severe sarcopenia in UC correlate with the disease activity.
RESUMEN
BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.
Asunto(s)
COVID-19 , Colecalciferol , SARS-CoV-2 , Deficiencia de Vitamina D , Humanos , Masculino , Femenino , Método Doble Ciego , Persona de Mediana Edad , COVID-19/mortalidad , COVID-19/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/complicaciones , Colecalciferol/administración & dosificación , Colecalciferol/uso terapéutico , Anciano , Vitamina D/sangre , Vitaminas/uso terapéutico , Vitaminas/administración & dosificación , Puntuaciones en la Disfunción de Órganos , Suplementos Dietéticos , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/mortalidad , Tratamiento Farmacológico de COVID-19 , Pandemias , Adulto , Resultado del Tratamiento , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/mortalidad , Índice de Severidad de la Enfermedad , BetacoronavirusRESUMEN
Neuroendocrine tumors (NETs) may mimic many endocrine syndromes, including Cushing syndrome (CS) secondary to ectopic ACTH secretion. Radiotherapy (RT) is often used as adjuvant therapy for such persistent or recurrent NETs. However, RT may predispose a susceptible person to a second malignancy. Here, we reported the story of a 37-year-old male, who presented with progressive weight loss, bone pain, and shortness of breath in the emergency department. He was diagnosed with CS secondary to a carcinoid tumor in the bronchopulmonary tree a decade previous and underwent total bilateral adrenalectomy. He also underwent lobectomy, and subsequent RT for a primary NET and was in clinical remission. His presenting symptoms were considered a recurrence of pulmonary NETs. However, the biopsy suggested high-grade mucoepidermoid carcinoma (MEC). MEC of the lung is a rare tumor with a prevalence of <1% of all lung malignancies. MEC of the lung after RT for bronchial NET-causing ectopic CS has not yet been reported in the literature. The present patient did not survive despite achieving remission of CS and primary tumor because of the aggressive second malignancy attributed to RT, which was given for the primary tumor.