Somatostatin receptor imaging of thyroid tissue and differentiated thyroid cancer using gallium-68-labeled radiotracers-a review of clinical studies.

INTRODUCTION: The rise in thyroid cancer incidence, especially papillary thyroid cancer (PTC), has underscored the need for improved diagnostic methods and management strategies. Herein, we aim to comprehensively review the evolving landscape in thyroid cancer diagnosis and the potential utility of Gallium-68 (Ga-68) based somatostatin receptor imaging. METHODS: We reviewed the clinical studies involving Ga-68 based radiotracers by looking at the following literature databases -PUBMED, EMBASE, WEB OF SCIENCE and COCHRANE. We employed a detailed search strategy with the following search terms; PubMed: ("gallium Ga 68 dotatate" [Supplementary Concept]) AND ("Thyroid Gland"[Mesh] OR "Thyroid Nodule"[Mesh] OR "Thyroid Neoplasms"[Mesh]), Embase ("gallium 68" AND "Thyroid Disease"), Web of Science: ("Gallium 68 and Thyroid"). RESULTS: A comparison between Ga-68 DOTATATE and Ga-68 DOTANOC showed similar sensitivities but a higher uptake for Ga-68 DOTATATE. Studies comparing Ga-68-based SSTR PET with FDG PET highlighted the potential advantages of both approaches, with Ga-68-based SSTR PET being more specific in certain cases. DISCUSSION: Ga-68-based somatostatin receptor imaging displays clinical utility in RAI-R DTC, offering valuable insight into detecting skeletal lymph node metastases. Notably, it shows potential as a primary imaging tool, potentially augmenting the role of FDG PET. However, SSTR PET imaging's efficacy in distinguishing benign from malignant thyroid nodules varies, with a complex interplay of factors influencing its specificity, indicating its value as an adjunct to existing methods, warranting further research for a refined role in thyroid cancer management. CONCLUSION: Although study variations exist, Ga-based somatostatin receptor imaging holds potential as a complementary tool alongside diagnostic methods in thyroid cancer diagnosis, with particular relevance to RAI-R DTC. In carefully selected patients demonstrating the presence of Ga-68 DOTATATE avid lesions, further exploration, and investigation into the potential utilization of Lu177 DOTATATE are warranted.

A Hypothetical Case Example Illustrating the Importance of a Multidisciplinary Approach to Treating Chronic/Functional Abdominal Pain in Pediatric Patients.

Irritable bowel syndrome (IBS) can have a substantial impact on the physical, academic, and psychosocial functioning of pediatric patients. As a functional gastrointestinal disorder, pediatric patients with IBS are thought to benefit from a multidisciplinary approach to target the biopsychosocial factors of this condition. In this co-authored article by a Pediatric Gastroenterologist, Pediatric Pain and Palliative Care specialist and Pediatric GI Psychologist, we present a hypothetical case of a pediatric patient who will undergo evaluation and treatment by each of these specialists demonstrating how a collaborative effort amongst multidisciplinary specialists is the ideal approach to care.

Bio-Mimicking Brain Vasculature to Investigate the Role of Heterogeneous Shear Stress in Regulating Barrier Integrity.

A continuous, sealed endothelial membrane is essential for the blood-brain barrier (BBB) to protect neurons from toxins present in systemic circulation. Endothelial cells are critical sensors of the capillary environment, where factors like fluid shear stress (FSS) and systemic signaling molecules activate intracellular pathways that either promote or disrupt the BBB. The brain vasculature exhibits complex heterogeneity across the bed, which is challenging to recapitulate in BBB microfluidic models with fixed dimensions and rectangular cross-section microchannels. Here, a Cayley-tree pattern, fabricated using lithography-less, fluid shaping technique in a modified Hele-Shaw cell is used to emulate the brain vasculature in a microfluidic chip. This geometry generates an inherent distribution of heterogeneous FSS, due to smooth variations in branch height and width. hCMEC/D3 endothelial cells cultured in the Cayley-tree designed chip generate a 3D monolayer of brain endothelium with branching hierarchy, enabling the study of the effect of heterogeneous FSS on the brain endothelium. The model is employed to study neuroinflammatory conditions by stimulating the brain endothelium with tumor necrosis factor-α under heterogeneous FSS conditions. The model has immense potential for studies involving drug transport across the BBB, which can be misrepresented in fixed dimension models.

Acute myocardial infarction in a young adult with hyperhomocysteinaemia secondary to tropical sprue.

Coronary heart disease and its complications remain the most common cause of morbidity and mortality throughout the world. In addition, its incidence among adults <45 years of age has also been steadily increasing in the past few decades. Besides the typical aetiology such as coronary artery abnormalities or autoimmune disorders, increasing rates can be attributed to escalating trends of obesity, type 2 diabetes mellitus, and illicit abuse of drugs such as cocaine and amphetamines in the younger population.1 Every cardiovascular event in a young adult must be thoroughly investigated as the aetiology is typically unconventional. Our case reports a young man who developed an acute inferior wall myocardial infarction (IWMI) in the setting of hyperhomocysteinaemia secondary to vitamin B12-folate deficiency itself due to tropical sprue.

Adult-onset adrenoleukodystrophy presenting with status epilepticus and psychosis.

Adrenoleukodystrophy (ALD) is an X linked recessive genetic disorder caused by an abnormality in the ABCD1 gene on the X chromosome, that affects 1 in 20 000 people. In X linked adrenoleukodystrophy (X-ALD), a defect in lignoceroyl-coenzyme A ligase causes pathognomonic tissue accumulation of very long chain fatty acids (VLCFA) in the adrenal cortex and nervous system. The phenotypic variability ranges from cerebral inflammatory demyelination of childhood onset, leading to death within 5 years, to adults remaining presymptomatic through more than five decades. Our case is that of a man who was previously diagnosed with bipolar affective disorder presented with dystonic posturing. During transit, he had an episode of generalised convulsive status epilepticus. He presented with spasticity and exaggerated reflexes. Three important signs of adrenal insufficiency were observed: hypotension, hyperpigmentation and comatose state. The diagnosis of X-ALD should be considered in young men presenting with gradually progressive unexplained cognitive and behavioural problems, a strong family history, adrenal insufficiency, bilateral upper motor signs with absent ankle reflexes.

Use of Lean Healthcare to Improve Hospital Throughput and Reduce LOS.

Improving the discharge process is an area of focus throughout healthcare organizations. Capacity constraints, efficiency improvement, patient safety, and quality care are driving forces for many discharge process workgroups. METHODS: Following the Pareto principle, we focused on improving the discharge process on the medical-surgical units that received the most patients admitted from the emergency department. Increased demand for medical-surgical beds, renovations, and diminished bed capacity made it imperative to improve efficiency using quality improvement techniques. A core team of frontline staff decreased the time between computer entry of discharge orders and patient's departure from the unit to less than 60 minutes, with 80% compliance. The team developed a daily dashboard that detailed the process and outcome measures to create situational awareness and daily visual management. Additional observations of staff workflow uncovered excessive walking for printer use. Printers were placed at the point of use to reduce transport times. Next, using survey results provided by patients on discharge quality, a Treasure Map that aided with teach-back and Team Discharge were implemented to level the staff's workload. Finally, physicians discharged patients earlier in the day. They standardized their discharge criteria to remove subjectivity from the discharge process and enable better team involvement. RESULTS: After implementing 4 interventions, the average time between computer entry of discharge orders and patient's departure from the unit decreased (94.26 versus 65.98 minutes; P < 0.001), simultaneously reducing our average length of stay from 5.62 to 4.81 days (P < 0.001). CONCLUSIONS: In conclusion, hardwiring proven interventions and complementing them with daily visual management led to significant, sustained results.

Essential thrombocythemia with portal vein thrombosis and splenic infarction successfully treated with platelet apheresis.

A 63-year-old diabetic woman presented to the outpatient clinic with a 1-week history of abdominal pain. On complete evaluation, she was diagnosed to have essential thrombocythemia. Abdominal imaging revealed portal vein thrombosis with a large splenic infarct. The patient was started on anticoagulant, antiplatelet and cytoreductive therapy. In view of persistent high platelet count, plasma apheresis was done, following which the patient's platelet counts were reduced. Essential thrombocythemia has a high rate of complications, resulting in significant morbidity and mortality. Few cases of this disease and its treatment have been described in the literature, especially pertaining to the Indian scenario. Further studies are needed to establish a multidisciplinary algorithm for its diagnosis and to elucidate the guidelines for the successful treatment of the condition.

COVID-19 Infection in Reproductive Age Group Females: Experience of a Tertiary Care Urban Teaching Hospital.

Background: The objective of this study was to find out the effect, course of disease and management of the COVID-19 infection in pregnant women and compare it with non-pregnant population. Method: This is a retrospective study done at Sardar Vallabhbhai Patel Institute of Medical Science and Research (SVPIMSR), Smt. NHL MMC, Ahmedabad, from April 1, 2020, to September 30, 2020. All COVID-19-positive patients were divided into two groups: group A was comprised of pregnant/postpartum and group B of non-pregnant patients. Result: A total of 709 women (Group A-205, Group B-504) were included in the study, In group A 90% of patients were asymptomatic, while in group B 48% asymptomatic patients. Group A had 5.9% and group B had 13.1% patients having comorbidities. In group A, smaller number of patients had raised inflammatory markers as compared to group B. Only 4% patients of group A showed significant changes on chest X-ray as compared to 16% in group B. Only 2.9% patients of group A required intensive care unit admission as compared to 10.31% patients of group B. Mean hospital stay of group A was 10.6 days, and that of group B was 12.1 days. Conclusion: In pregnancy, due to the physiological alterations in cardiovascular, respiratory and immune system, the pregnant women are vulnerable to infections. Although pregnancy is immunocompromised state, the severity of Coivd-19 disease is milder as compared to non-pregnant COVID-19-positive patients.

Development of Polymeric Nanoparticles for Blood-Brain Barrier Transfer-Strategies and Challenges.

Neurological disorders such as Alzheimer's disease, stroke, and brain cancers are difficult to treat with current drugs as their delivery efficacy to the brain is severely hampered by the presence of the blood-brain barrier (BBB). Drug delivery systems have been extensively explored in recent decades aiming to circumvent this barrier. In particular, polymeric nanoparticles have shown enormous potentials owing to their unique properties, such as high tunability, ease of synthesis, and control over drug release profile. However, careful analysis of their performance in effective drug transport across the BBB should be performed using clinically relevant testing models. In this review, polymeric nanoparticle systems for drug delivery to the central nervous system are discussed with an emphasis on the effects of particle size, shape, and surface modifications on BBB penetration. Moreover, the authors critically analyze the current in vitro and in vivo models used to evaluate BBB penetration efficacy, including the latest developments in the BBB-on-a-chip models. Finally, the challenges and future perspectives for the development of polymeric nanoparticles to combat neurological disorders are discussed.

Efficacy of combination therapy of inositols, antioxidants and vitamins in obese and non-obese women with polycystic ovary syndrome: an observational study.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of both developed and developing countries. It is associated with insulin resistance, hyperinsulinemia, hyperandrogenism, oxidative stress and various long-term complications. The present study was undertaken to evaluate the efficacy and safety of the supplementation (Trazer F ForteTM-CORONA Remedies Pvt. Ltd.) providing combination of insulin sensitising agents (myo-inositol, D-chiro-inositol and chromium picolinate), antioxidants (N-acetylcysteine and lycopene) and vitamins (vitamin D, biotin and folic acid) in women with PCOS. After 12 weeks of supplementation, a significant improvement was observed in menstrual cyclicity, acne and hirsutism in both obese and lean PCOS patients. A significant reduction was observed in body weight and BMI of obese subjects. However, both parameters remain unchanged in lean subjects. We suggest that combination therapy of insulin sensitising agents, antioxidants and vitamins may be a fruitful approach for the management of PCOS.Impact statementWhat is already known on this subject? Monotherapy of insulin sensitising agents, antioxidants and vitamins is beneficial in the treatment of PCOS.What do the results of this study add? Combined use of insulin sensitising agents (myo-inositol, D-chiro-inositol and chromium picolinate), antioxidants (N-acetylcysteine and lycopene), and vitamins (vitamin D, biotin and folic acid) is safe and effective in obese and non-obese women with PCOS.What are the implications of these findings for clinical practice and/or further research? Since PCOS is a multifactorial and a complex endocrine disorder, combination therapy can be used for the comprehensive management of PCOS.

Role of Preferential Ions of Ammonium Ionic Liquid in Destabilization of Collagen.

Ions play a key role in the destabilization of collagen. This study explores the effect of diethyl methyl ammonium methane sulfonate (AMS), an ionic liquid (IL), on different hierarchical orderings of collagen, namely, at the molecular and fibrillar levels. The rheological behavior and secondary structural changes reveal changes in the hydrogen-bonding environment of collagen, leading to alterations in the triple helical structure of collagen. An increase in the concentration of AMS resulted in swelling of rat-tail tendon fibers, and also, decreased thermal stability signifies that ions are obliged to destabilize collagen at the fibrillar level. Molecular modeling studies confirm that anions are judiciously held responsible for structural deformities in collagen, whereas cations have a tenuous effect. Thus, the preferential role of ions present in an ammonium IL has been elucidated in this study.

Electrostatic Forces Mediated by Choline Dihydrogen Phosphate Stabilize Collagen.

Cross-linkers aid in improving biostability of collagen via different mechanisms. Choline dihydrogen phosphate (cDHP), a biocompatible ionic liquid, has been reported as a potential cross-linker for collagen. However, its mechanism is yet unclear. This study explores the effect of cDHP on the physicochemical stability of collagen and nature of its interaction. Dielectric behavior of collagen-cDHP composites signifies that cDHP enhances intermolecular forces. This was demonstrated by an increase in cross-linked groups and high denaturation temperature of collagen-cDHP composites. XRD measurements reveal minor conformational change in helices. Molecular modeling studies illustrate that the force existing between collagen and cDHP is electrostatic in nature. Herein, it is postulated that dihydrogen phosphate anion attaches to cationic functional groups of collagen, resulting in closer vicinity of various side chains of collagen, forming physical and chemical cross-links within collagen, contributing to its structural stability. Our study suggests that dihydrogen phosphate anions can be employed for developing a new class of biocompatible cross-linkers.

Can green solvents be alternatives for thermal stabilization of collagen?

"Go Green" campaign is gaining light for various industrial applications where water consumption needs to be reduced. To resolve this, industries have adopted usage of green, organic solvents, as an alternative to water. For leather making, tanning industry consumes gallons of water. Therefore, for adopting green solvents in leather making, it is necessary to evaluate its influence on type I collagen, the major protein present in the skin matrix. The thermal stability of collagen from rat tail tendon fiber (RTT) treated with seven green solvents namely, ethanol, ethyl lactate, ethyl acetate, propylene carbonate, propylene glycol, polyethylene glycol-200 and heptane was determined using differential scanning calorimetry (DSC). Crosslinking efficiency of basic chromium sulfate and wattle on RTT in green solvents was determined. DSC thermograms show increase in thermal stability of RTT collagen against heat with green solvents (>78°C) compared to water (63°C). In the presence of crosslinkers, RTT demonstrated thermal stability >100°C in some green solvents, resulting in increased intermolecular forces between collagen, solvent and crosslinkers. The significant improvement in thermal stability of collagen potentiates the capability of green solvents as an alternative for water.

Effect of ionic liquids on the different hierarchical order of type I collagen.

The effect of ionic liquids (ILs) on proteins has been gaining huge interest due to easy tunability of cation and anion for generating the desired effect. This study explores the effect of alkyl imidazolium chloride ILs on collagen at molecular, inter-fibrillar and skin matrix level. Circular dichroic studies reveal that at the molecular level, the secondary structure of collagen was not affected by imidazolium ILs and there was no change in thermal stability as well. However, collagen at the inter-fibrillar level behaved differently. With increase in concentration of ILs, remarkable decrease in thermal stability of rat tail tendon (RTT) collagen fibers with marginal swelling effect was seen. SEM micrographs of skin matrix treated with IL show opening up of pores. This kind of exquisite behavior of ILs at different hierarchal order of collagen indicates that ILs are endowed with potential lyotropic action, which can be judiciously employed for biomedical applications.

Deficits in mental state attributions in individuals with 22q11.2 deletion syndrome (velo-cardio-facial syndrome).

Velo-cardio-facial syndrome (VCFS; 22q11.2 deletion syndrome) results from a genetic mutation that increases risk for Autism Spectrum Disorder (ASD). We compared Theory of Mind (ToM) skills in 63 individuals with VCFS (25% with an ASD diagnosis) and 43 typically developing controls, and investigated the relationship of ToM to reciprocal social behavior. We administered a video-based task to assess mentalizing at two sites University of California, Los Angeles (UCLA) and State University of New York (SUNY) Upstate Medical University. The videos depicted interactions representing complex mental states (ToM condition), or simple movements (Random condition). Verbal descriptions of the videos were rated for Intentionality (i.e. mentalizing) and Appropriateness. Using Repeated Measures analysis of variance (ANOVA), we assessed the effects of VCFS and ASD on Intentionality and Appropriateness, and the relationship of mentalizing to Social Responsiveness Scale (SRS) scores. Results indicated that individuals with VCFS overall had lower Intentionality and Appropriateness scores than controls for ToM but not for Random scenes. In the SUNY sample, individuals with VCFS, both with and without ASD, performed more poorly than controls on the ToM condition; however, in the UCLA sample, only individuals with VCFS without ASD performed significantly worse than controls on the ToM condition. Controlling for site and age, performance on the ToM condition was significantly correlated with SRS scores. Individuals with VCFS, regardless of an ASD diagnosis, showed impairments in the spontaneous attribution of mental states to abstract visual stimuli, which may underlie real-life problems with social interactions. A better understanding of the social deficits in VCFS is essential for the development of targeted behavioral interventions.

Social-adaptive and psychological functioning of patients affected by Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P < 0.01), anxiety (P = 0.05), depression and anxiety (P = 0.03), antisocial personality (P < 0.001), attention-deficit/hyperactivity (AD/H; P < 0.01), hyperactivity-impulsivity (P < 0.01), and aggressive behavior (P = 0.03) were associated with poorer adaptive functioning. Decreased social-adaptive functioning in this study was not statistically significantly associated to disease severity, pain, or level of vitality. This study shows for the first time that FD patients, particularly women, are affected by decreased social-adaptive functioning. Comprehensive treatment plans for FD should consider assessments and interventions to evaluate and improve social, occupational, and psychological functioning. Attention to the behavioral aspects of FD could lead to improved treatment outcome and improved quality of life. Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety, depression, antisocial behavior, and AD/H problems in a sampling of our male and female patients aged between 18 years and 59 years.