Recent Data about the Use of Corticosteroids in Sepsis-Review of Recent Literature.

Sepsis, characterized by life-threatening organ dysfunction due to a maladaptive host response to infection, and its more severe form, septic shock, pose significant global health challenges. The incidence of these conditions is increasing, highlighting the need for effective treatment strategies. This review explores the complex pathophysiology of sepsis, emphasizing the role of the endothelium and the therapeutic potential of corticosteroids. The endothelial glycocalyx, critical in maintaining vascular integrity, is compromised in sepsis, leading to increased vascular permeability and organ dysfunction. Corticosteroids have been used for over fifty years to treat severe infections, despite ongoing debate about their efficacy. Their immunosuppressive effects and the risk of exacerbating infections are significant concerns. The rationale for corticosteroid use in sepsis is based on their ability to modulate the immune response, promote cardiovascular stability, and potentially facilitate organ restoration. However, the evidence is mixed, with some studies suggesting benefits in terms of microcirculation and shock reversal, while others report no significant impact on mortality or organ dysfunction. The Surviving Sepsis Campaign provides cautious recommendations for their use. Emerging research highlights the importance of genomic and transcriptomic analyses in identifying patient subgroups that may benefit from corticosteroid therapy, suggesting a move toward personalized medicine in sepsis management. Despite potential benefits, the use of corticosteroids in sepsis requires careful consideration of individual patient risk profiles, and further research is needed to optimize their use and integrate genomic insights into clinical practice. This review underscores the complexity of sepsis treatment and the ongoing need for evidence-based approaches to improve patient outcomes.

The Future Direction of Women in Nuclear Medicine and Nuclear Medicine in Women's Health.

This work discusses the role of Nuclear Medicine for women's health, the role of women in the development of this emerging field and the various issues which arise from both. It emphasizes the importance of young women and their competing needs due to factors like pregnancy and work-related challenges. The objectives of this overview include improving imaging techniques, preserving fertility during cancer treatment, diagnosing pelvic and uterine conditions, developing radiopharmaceuticals for women's health, protecting female employees in Nuclear Medicine, and considering the role of artificial intelligence.

Total Psoas Area and Psoas Density Assessment in COVID-19 Patients Using CT Imaging - Could Muscle Mass Alteration During Intensive Care Hospitalization be Determined?

Background: Since its debut, as reported by the first published studies, COVID-19 has been linked to life-threatening conditions that needed vital assistance and admission to the intensive care unit. Skeletal muscle is a core element in an organism's health due to its ability to keep energy balance and homeostasis. Many patients with prolonged hospitalization are characterized by a greater probability prone to critical illness myopathy or intensive care unit-acquired weakness. Objective: The main aim of this study was to assess the skeletal muscle in a COVID-19 cohort of critically ill patients by measuring the psoas area and density. Material and methods: This is a retrospective study that included critically ill adult patients, COVID-19 positive, mechanically ventilated, with an ICU stay of over 24 hours, and who had 2 CT scans eligible for psoas muscle evaluation. In these patients, correlations between different severity scores and psoas CT scans were sought, along with correlations with the outcome of the patients. Results: Twenty-two patients met the inclusion criteria. No statistically significant differences were noticed regarding the psoas analysis by two blinded radiologists. Significant correlations were found between LOS in the hospital and in ICU with psoas area and Hounsfield Units for the first CT scan performed. With reference to AUC-ROC and outcome, it is underlined that AUC-ROC is close to 0.5 values, for both the psoas area and HU, indicating that the model had no class separation capacity. Conclusion: The study suggested that over a short period, the psoas muscle area, and the psoas HU decline, for both the left and the right sight, in adult COVID-19 patients in ICU conditions, yet not statistically significant. Although more than two-thirds of the patients had a negative outcome, it was not possible to demonstrate an association between the SARS-COV2 infection and psoas muscle impairment. These findings highlight the need for further larger investigations.

Assessment of the Diaphragm Thickness Decrease in Critically Ill COVID-19 Patients: Could Computed Tomography Be of Aid Regarding Diaphragm Muscle Mass?

INTRODUCTION: The diaphragm has a significant clinical value on respiratory performance. There is little literature on the use of thorax computed tomography for the purpose of identifying alterations in diaphragm thickness in critically ill patients diagnosed with COVID-19. The present study aims to investigate dynamic changes in muscle thickness and its association with clinical outcomes. METHODS: A single-center retrospective observational study was conducted in a tertiary intensive care unit (ICU). The study comprised adult patients with severe COVID-19 who were admitted to the ICU and underwent two thorax CT scans. We measured diaphragmatic thickness at the level of the celiac truncus. RESULTS: The average reduction in thickness of the dynamic diaphragm was found to be -0.58 mm for the right diaphragm and -0.54 mm for the left diaphragm. The diaphragm thickness exhibited a substantial decrease on both the right and left sides in both CT scans (p=0.02). A negative correlation coefficient was observed for both the right and left diaphragm. The criterion indicating a poor prognosis for the right diaphragm was a value greater than -0.175, whereas it was more significant for the left diaphragm than -0.435. The cut-off values indicated a high risk of prolonged mechanical ventilation and an increased risk of ICU mortality. CONCLUSION:  CT diaphragm evaluation in mechanically ventilated COVID-19 patients has the possibility of becoming a reliable tool for predicting muscle modifications.

LC-MS/MS assisted biomonitoring of ropivacaine and 3-OH-ropivacaine after plane block anesthesia for cardiac device implantation.

Introduction: Ropivacaine is a popular local anesthetic used for regional anesthesia or for pain management. Although designed as an enantiomerically pure drug, an aspect that reduces the adverse effects, its toxicological effects are still a risk. As such, biomonitoring to assure appropriate dosage and bioavailability are essential to avoid complications during or post-surgery. Methods: The study focused on developing a sensitive, selective, and accurate liquid chromatography-mass spectrometry (LCMS/MS) method which facilitates the biomonitoring of ropivacaine and its main metabolite in plasma after regional anesthesia using ropivacaine. Results and Discussion: The method was validated with regards to all relevant parameters, such as sensitivity, selectivity, accuracy, precision, and the effect of sample matrix. The method was successfully used in a pilot study, which included one patient undergoing plane block anesthesia for cardiac device implantation. The results showed the method is appropriate for its intended purpose and could even be used in other, similar applications.

Quantitative vs. Qualitative SPECT-CT Diagnostic Accuracy in Bone Lesion Evaluation-A Review of the Literature.

(1) Background: Considering the importance that quantitative molecular imaging has gained and the need for objective and reproducible image interpretation, the aim of the present review is to emphasize the benefits of performing a quantitative interpretation of single photon emission computed tomography-computed tomography (SPECT-CT) studies compared to qualitative interpretation methods in bone lesion evaluations while suggesting new directions for research on this topic. (2) Methods: By conducting comprehensive literature research, we performed an analysis of published data regarding the use of quantitative and qualitative SPECT-CT in the evaluation of bone metastases. (3) Results: Several studies have evaluated the diagnostic accuracy of quantitative and qualitative SPECT-CT in differentiating between benign and metastatic bone lesions. We collected the sensitivity and specificity for both quantitative and qualitative SPECT-CT; their values ranged between 74-92% and 81-93% for quantitative bone SPECT-CT and between 60-100% and 41-100% for qualitative bone SPECT-CT. (4) Conclusions: Both qualitative and quantitative SPECT-CT present an increased potential for better differentiating between benign and metastatic bone lesions, with the latter offering additional objective information, thus increasing diagnostic accuracy and enabling the possibility of performing treatment response evaluation through accurate measurements.

Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Axillary Conversion after Neoadjuvant Chemotherapy-A Single-Tertiary Centre Experience and Review of the Literature.

(1) Introduction: Sentinel lymph node biopsy (SLNB) is widely used in breast cancer patients who undergo neoadjuvant chemotherapy (NAC), replacing axillary lymph node dissection. While commonly accepted for cN0 patients, its role in cN1/2 patients remains controversial. Our study aims to investigate the role of SLNB in BC patients who underwent prior NAC and compare our results to those of other studies presented in the literature. (2) Materials and methods: Our retrospective study included 102 breast cancer patients who received NAC before 99mTc-albumin Nanocolloid SLN mapping and SLNB was performed, completed or not with axillary dissection. A review based on the PRISMA statement was also carried out, encompassing 20 studies. (3) Results: The lymphoscintigraphy performed after the administration of NAC presented an identification rate (IR) of 93.13%. IR for SLNB was 94.11%, with a false-negative rate (FNR) of 7.4%. After a median follow-up of 31.3 months, we obtained a distant disease-free survival rate of 98%. The results obtained by other groups were similar to those of our study, presenting IR in the range 80.8-96.8%, with FNR varying from 0 to 22%. (4) Conclusions: on conclusion, SLNB can accurately determine the lymph node status, with an acceptable FNR and maintain its expected prognostic role with low recurrence rates, and our results are comparable to those obtained by other studies.

Quantitative SPECT/CT Parameters in the Assessment of Transthyretin Cardiac Amyloidosis-A New Dimension of Molecular Imaging.

AIMS: Cardiac transthyretin amyloidosis (ATTR) represents the accumulation of misfolded transthyretin in the heart interstitium. Planar scintigraphy with bone-seeking tracers has long been established as one of the three main steps in the non-invasive diagnosis of ATTR, but lately, single-photon emission computed tomography (SPECT) has gained wide recognition for its abilities to exclude false positive results and offer a possibility for amyloid burden quantitation. We performed a systematic review of the existing literature to provide an overview of the available SPECT-based parameters and their diagnostic performances in the assessment of cardiac ATTR. Methods and Methods: Among the 43 papers initially identified, 27 articles were screened for eligibility and 10 met the inclusion criteria. We summarised the available literature based on radiotracer, SPECT acquisition protocol, analysed parameters and their correlation to planar semi-quantitative indices. RESULTS: Ten articles provided accurate details about SPECT-derived parameters in cardiac ATTR and their diagnostic potential. Five studies performed phantom studies for accurate calibration of the gamma cameras. All papers described good correlation of quantitative parameters to the Perugini grading system. CONCLUSIONS: Despite little published literature on quantitative SPECT in the assessment of cardiac ATTR, this method offers good prospects in the appraisal of cardiac amyloid burden and treatment monitoring.

Diffusion-Enhanced Förster Resonance Energy Transfer in Flexible Peptides: From the Haas-Steinberg Partial Differential Equation to a Closed Analytical Expression.

In the huge field of polymer structure and dynamics, including intrinsically disordered peptides, protein folding, and enzyme activity, many questions remain that cannot be answered by methodology based on artificial intelligence, X-ray, or NMR spectroscopy but maybe by fluorescence spectroscopy. The theory of Förster resonance energy transfer (FRET) describes how an optically excited fluorophore transfers its excitation energy through space to an acceptor moiety-with a rate that depends on the distance between donor and acceptor. When the donor and acceptor moiety are conjugated to different sites of a flexible peptide chain or any other linear polymer, the pair could in principle report on chain structure and dynamics, on the site-to-site distance distribution, and on the diffusion coefficient of mutual site-to-site motion of the peptide chain. However, the dependence of FRET on distance distribution and diffusion is not defined by a closed analytical expression but by a partial differential equation (PDE), by the Haas-Steinberg equation (HSE), which can only be solved by time-consuming numerical methods. As a second complication, time-resolved FRET measurements have thus far been deemed necessary. As a third complication, the evaluation requires a computationally demanding but indispensable global analysis of an extended experimental data set. These requirements have made the method accessible to only a few experts. Here, we show how the Haas-Steinberg equation leads to a closed analytical expression (CAE), the Haas-Steinberg-Jacob equation (HSJE), which relates a diffusion-diagnosing parameter, the effective donor-acceptor distance, to the augmented diffusion coefficient, J, composed of the diffusion coefficient, D, and the photophysical parameters that characterize the used FRET method. The effective donor-acceptor distance is easily retrieved either through time-resolved or steady-state fluorescence measurements. Any global fit can now be performed in seconds and minimizes the sum-of-square difference between the experimental values of the effective distance and the values obtained from the HSJE. In summary, the HSJE can give a decisive advantage in applying the speed and sensitivity of FRET spectroscopy to standing questions of polymer structure and dynamics.

Quantitative Assessment of Treatment Response in Metastatic Breast Cancer Patients by SPECT-CT Bone Imaging-Getting Closer to PET-CT.

BACKGROUND: Cancer represents the major cause of death mainly through its ability to spread to other organs, highlighting the importance of metastatic disease diagnosis and accurate follow up for treatment management purposes. Although until recently the main method for imaging interpretation was represented by qualitative methods, quantitative analysis of SPECT-CT data represents a viable, objective option. METHODS: Seventy-five breast cancer patients presenting metastatic bone disease underwent at least two Bone SPECT-CT studies using [99mTc]-HDP between November 2019 to October 2022. RESULTS: Our findings show a good positive relationship between the qualitative methods of imaging interpretation and quantitative analysis, with a correlation coefficient of 0.608 between qualitative whole body scintigraphy and quantitative SPECT-CT, and a correlation coefficient of 0.711 between the qualitative and quantitative interpretation of SPECT-CT data; nevertheless, there is a need for accurate, objective and reproducible methods for imaging interpretation, especially for research purposes. CONCLUSIONS: Quantitative evaluation of the SPECT-CT data has the potential to be the first choice of imaging interpretation for patient follow up and treatment response evaluation, especially for research purposes, because of its objectivity and expression of uptake changes in absolute units.

Standardized Uptake Values on SPECT/CT: A Promising Alternative Tool for Treatment Evaluation and Prognosis of Metastatic Neuroendocrine Tumours.

(1) Background: The aim of our study was to assess the feasibility of 99mTcEDDA/HYNIC-TOC SPECT/CT quantitative analysis in evaluating treatment response and disease progression in patients with NETs. (2) Methods: This prospective monocentric study evaluated 35 SPECT/CT examinations performed on 14 patients with neuroendocrine tumours who underwent a baseline and at least one follow-up 99mTcEDDA/HYNIC-TOC scan as part of their clinical management. The examination protocol included a whole-body scan acquired 2 h after the radiotracer's administration, with the SPECT/CT performed 4 h post-injection. Images were analyzed by two experienced physicians and patients were classified into response categories based on their changes in SUV values. (3) Results: We evaluated 14 baseline studies and 21 follow-up scans, accounting for 123 lesions. A statistically positive correlation has been found between the SUVmax and SUVpeak values in tumoral lesions (p < 0.05). No correlation has been found between the SUV values and the ki67 proliferation index. Finally, 64.29% patients were classified as SD at the end of the study, with only 14.29% of patients exhibiting PD and 21.43% patients with PR. (4) Conclusions: The quantitative analysis of 99mTcEDDA/HYNIC-TOC SPECT/CT data in patients with neuroendocrine tumours could represent an alternative to 68Ga-DOTA-peptides PET/CT for the monitoring and prognosis of NETs.

Pharmacological Inhibition of Lysine-Specific Demethylase 1A Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Deficient Mice by a Mechanism Involving Decreased Oxidative Stress and Inflammation; Potential Implications in Human Atherosclerosis.

Dysregulated epigenetic mechanisms promote transcriptomic and phenotypic alterations in cardiovascular diseases. The role of histone methylation-related pathways in atherosclerosis is largely unknown. We hypothesize that lysine-specific demethylase 1A (LSD1/KDM1A) regulates key molecular effectors and pathways linked to atherosclerotic plaque formation. Human non-atherosclerotic and atherosclerotic tissue specimens, ApoE-/- mice, and in vitro polarized macrophages (Mac) were examined. Male ApoE-/- mice fed a normal/atherogenic diet were randomized to receive GSK2879552, a highly specific LSD1 inhibitor, or its vehicle, for 4 weeks. The mRNA and protein expression levels of LSD1/KDM1A were significantly elevated in atherosclerotic human carotid arteries, atherosclerotic aortas of ApoE-/- mice, and M1-Mac. Treatment of ApoE-/- mice with GSK2879552 significantly reduced the extent of atherosclerotic lesions and the aortic expression of NADPH oxidase subunits (Nox1/2/4, p22phox) and 4-hydroxynonenal-protein adducts. Concomitantly, the markers of immune cell infiltration and vascular inflammation were significantly decreased. LSD1 blockade down-regulated the expression of genes associated with Mac pro-inflammatory phenotype. Nox subunit transcript levels were significantly elevated in HEK293 reporter cells overexpressing LSD1. In experimental atherosclerosis, LSD1 mediates the up-regulation of molecular effectors connected to oxidative stress and inflammation. Together, these data indicate that LSD1-pharmacological interventions are novel targets for supportive therapeutic strategies in atherosclerosis.

Airway Ultrasound for Anesthesia and in Intensive Care Patients-A Narrative Review of the Literature.

Ultrasound is an everyday diagnostic tool. In anesthesia and intensive care, it has a role as an adjuvant for many procedures, including the evaluation of the airway. Ultrasound airway evaluation can help predict a difficult airway, visualize the proper positioning of an intubation cannula, or evaluate the airway post-intubation. Protocols need to be established for the better integration of ultrasound in the airway evaluation, however until a consensus is reached in this respect, the ultrasound is a reliable aid in anesthesia and intensive care.

Understanding COVID Vaccination and Its Implication in Cancer Patients' Imaging of Lymph Nodes by PET-CT.

(1) Background: The appearance of enlarged lymph nodes on imaging adds another layer of complexity to the differential diagnosis of disease progression versus immune response to COVID-19 vaccines. Our aim was to find an optimal timing between the vaccination and the PET-CT scan. (2) Methods: 25 cancer patients with 18F-FDG PET-CT evaluations and a history of COVID-19 vaccination between September 2021 and December 2021 were retrospectively analyzed to characterize the lymph nodes related to the time interval from COVID vaccination. (3) Results: All patients presented one or more adenopathies localized in the ipsilateral axilla (96%), ipsilateral cervical area (20%), ipsilateral retropectoral (20%) and pulmonary hilum (8%). The median value of SUVmax was 3.5 ± 0.5. There was a significant indirect correlation between SUVmax and the time passed between the vaccination and the PET CT (Pearson Correlation r = -0.54, p = 0.005). There was no significant difference (p = 0.19) in the SUVmax value in patients receiving Moderna mRNA-1273 vaccine vs. BNT162b2 mRNA Pfizer vaccine. (4) Conclusions: Lymph node enlargement is commonly seen in patients post-vaccination for COVID-19 and must be differentiated from disease progression. The data from our study strongly suggests that the minimum interval of time between an mRNA vaccine and a PET-CT should be more than six weeks.

Survey on Anxiety and Post-Traumatic Stress Disorder in Intensive Care Personnel during the COVID-19 Pandemic in a Medically Under-Resourced Country.

The COVID-19 pandemic has increased the need for intensive care personnel. Romania has a low number of physicians per inhabitant. The stress of pandemics upon an already weak medical health system triggered some psychological effects upon burnt-out personnel. The main objective is to provide an insight into the psychological status of Romanian ICU personnel by evaluating their level of anxiety. The secondary objectives aim to identify the level of post-traumatic stress disorder and anxiety in different groups and to identify the personnel most affected psychologically. This study enrolled adult responders from the ICU of Târgu Mureș Emergency Clinical County Hospital, Romania, participating voluntarily. The evaluation tests were the State-Trait Anxiety Inventory and Post-Traumatic Stress Test. Out of the 126 eligible participants, 87 adult employees were enrolled-with a 69% response rate. The study comprised three groups: doctors, nurses, and auxiliary personnel. All three groups scored for moderate anxiety symptoms. COVID-19-related anxiety was strongly correlated with age and number of working years in all groups. Increased PTSD scores were observed in doctors and nurses. All ICU personnel who dealt with COVID-19 patients presented with moderate anxiety and post-traumatic stress disorder symptoms. The years of ICU experience had a positive impact on anxiety symptoms.

The New Radiolabeled Peptide 99mTcEDDA/HYNIC-TOC: Is It a Feasible Choice for Diagnosing Gastroenteropancreatic NETs?

(1) Background: The aim of our study is to reveal the advantages and limitations of the use of 99mTcEDDA/HYNIC-TOC (Tektrotyd®, Polatom) in the diagnosis of gastroenteropancreatic neuroendocrine tumors and to compare our results with the values obtained for 111In-pentetreotide and 68Ga-DOTA-peptides, routinely used in medical practice. (2) Methods: This retrospective monocentric study included 173 patients with gastroenteropancreatic neuroendocrine tumors who underwent 99mTcEDDA/HYNIC-TOC scans as part of their clinical management. The examination protocol included a whole-body scan acquired 2 h after the radiotracer's administration, with the SPECT/CT performed 4 h post-injection. Physiological and abnormal uptake were established by two experienced physicians and, based on the obtained results, sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated. (3) Results: Our method presented a sensitivity of 90.5%, a specificity of 71.9%, and an accuracy of 84.3%, with a positive predictive value of 86.7% and a negative predictive value of 78.8%. (4) Conclusions: 99mTc-EDDA/HYNIC-TOC, a receptor-based radiopharmaceutical, could represent a competitor for 68Ga-labeled peptides in the diagnosis and management of patients with gastroenteropancreatic neuroendocrine tumors. Our results show a lower sensitivity (90.5%) than 68Ga-DOTA-peptides, but with great specificity, accuracy, positive, and negative predictive values.

Cardio Protective Effects of Lipid Emulsion against Ropivacaine-Induced Local Anesthetic Systemic Toxicity-An Experimental Study.

Inadvertent intravascular injection of local anesthetics (LA) during regional anesthesia causes Local Anesthetic Systemic Toxicity (LAST). Theories of lipid rescue in the case of LAST proved that the administration of lipids in LAST has beneficial effects. One possible mechanism of action is based on the lipophilic properties of LA which allow plasma-free LA to be bound by the molecules of Lipid Emulsion (LE). The association LA-LE is shuttled towards organs such as liver and the kidneys, and the half-life of LA is shortened. The main objective of this experimental study was to assess the possible cardio-prophylactic effect of LE administration before the induction of LAST by intravenous administration of Ropivacaine. This was an experimental, interventional, prospective, and non-randomized study. The subjects were divided into groups and received, under general anesthesia, LE 20% first 0.3-0.4 mL, followed by 0.1 mL Ropivacaine 2 mg/mL, or Ropivacaine alone. At the end of the experiment, the subjects were sacrificed, and tissue samples of kidney, heart and liver were harvested for histopathological examination. LE, when administered as prophylaxis in Ropivacaine-induced LAST, had protective cardiac effects in rats. The LE known side effects were not produced if the substance was administered in the low doses used for LAST prophylaxis.

Radiomics Analysis of [18F]FDG PET/CT Thyroid Incidentalomas: How Can It Improve Patients' Clinical Management? A Systematic Review from the Literature.

BACKGROUND: We performed a systematic review of the literature to provide an overview of the application of PET-based radiomics of [18F]FDG-avid thyroid incidentalomas and to discuss the additional value of PET volumetric parameters and radiomic features over clinical data. METHODS: The most relevant databases were explored using an algorithm constructed based on a combination of terms related to our subject and English-language articles published until October 2021 were considered. Among the 247 identified articles, 19 studies were screened for eligibility and 11 met the criteria, with 4 studies including radiomics analyses. RESULTS: We summarized the available literature based on a study of PET volumetric parameters and radiomics. Ten articles provided accurate details about volumetric parameters and their prospective value in tumour assessment. We included the data provided by these articles in a sub-analysis, but could not obtain statistically relevant results. Four publications analyzed the diagnostic potential of radiomics and the possibility of creating precise predictive models, their corresponding quality score being assessed. CONCLUSIONS: The use of PET volumetric parameters and radiomics analysis in patients with [18F]FDG-avid thyroid incidentalomas outlines a great prospect in diagnosis and stratification of patients with malignant nodules and may represent a way of limiting the need for unnecessary invasive procedures; however, further studies need to be performed for a standardization of the method.

Quantitative Analysis of SPECT-CT Data in Metastatic Breast Cancer Patients-The Clinical Significance.

PURPOSE: To assess the potential added value of the SPECT-CT quantitative analysis in metastatic breast cancer lesions detection and differentiation from degenerative lesions. METHODS: This prospective monocentric study was conducted on 70 female patients who underwent SPECT-CT bone scans using 99mTc-HDP that identified the presence of metastatic bone lesions and degenerative lesions in each patient. Once the lesions were identified, a quantitative analysis of radiotracer uptake was conducted. The highest one to five SUVmax values for both metastatic and degenerative bone lesions were identified in each patient and the data were then statistically analyzed. RESULTS: The SUVmax value was significantly higher in metastatic bone lesions than in degenerative lesions (p < 0.001). The diagnostic accuracy of SPECT-CT quantitative data analysis revealed a sensitivity of 91.5% and a specificity of 93.3% at a cut-off value of the SUVmax of 16.6 g/mL. CONCLUSION: Quantitative analysis performed using SPECT-CT data can improve the diagnostic accuracy in differentiating between metastatic bone lesions and degenerative lesions, thus leading to appropriate treatment and better follow-up in metastatic breast cancer patients.

Electrostatically induced pKa shifts in oligopeptides: the upshot of neighboring side chains.

pKa values of homorepeat hexapeptides with a 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) chromophore attached at the peptide C termini, through an asparagine derivative (Dbo), namely His6-Dbo (H6), Lys6-Dbo (K6), and Arg6-Dbo (R6), were determined by a novel fluorescence-based method. The fluorescence lifetime of Dbo in the peptides (τ) was measured as a function of pH. The side chains collide with Dbo intramolecularly and quench it efficiently only when they are deprotonated (i.e., pH ≥ side chain pKa). The pKa values of the H6, K6, and R6 peptides, attributable to side chain ionization, were found to be depressed compared to the pKa values of the His, Lys, and Arg residues in their free amino acid forms. We further looked into the structural changes of the peptides by molecular dynamics (MD) simulations; the peptides were structurally more expanded when their side chains are protonated. The structural expansion of the peptides reflects an electrostatic repulsion between the protonated side chain residues, which also accounts for the observed decrease in pKa values, which corresponds to a facilitated deprotonation, assisted by electrostatic repulsion.