Recent developments in time-of-flight PET

While the first time-of-flight (TOF)-positron emission tomography (PET) systems were already built in the early 1980s, limited clinical studies were acquired on these scanners. PET was still a research tool, and the available TOF-PET systems were experimental. Due to a combination of low stopping power and limited spatial resolution (caused by limited light output of the scintillators), these systems could not compete with bismuth germanate (BGO)-based PET scanners. Developments on TOF system were limited for about a decade but started again around 2000. The combination of fast photomultipliers, scintillators with high density, modern electronics, and faster computing power for image reconstruction have made it possible to introduce this principle in clinical TOF-PET systems. This paper reviews recent developments in system design, image reconstruction, corrections, and the potential in new applications for TOF-PET. After explaining the basic principles of time-of-flight, the difficulties in detector technology and electronics to obtain a good and stable timing resolution are shortly explained. The available clinical systems and prototypes under development are described in detail. The development of this type of PET scanner also requires modified image reconstruction with accurate modeling and correction methods. The additional dimension introduced by the time difference motivates a shift from sinogram- to listmode-based reconstruction. This reconstruction is however rather slow and therefore rebinning techniques specific for TOF data have been proposed. The main motivation for TOF-PET remains the large potential for image quality improvement and more accurate quantification for a given number of counts. The gain is related to the ratio of object size and spatial extent of the TOF kernel and is therefore particularly relevant for heavy patients, where image quality degrades significantly due to increased attenuation (low counts) and high scatter fractions. The original calculations for the gain were based on analytical methods. Recent publications for iterative reconstruction have shown that it is difficult to quantify TOF gain into one factor. The gain depends on the measured distribution, the location within the object, and the count rate. In a clinical situation, the gain can be used to either increase the standardized uptake value (SUV) or reduce the image acquisition time or administered dose. The localized nature of the TOF kernel makes it possible to utilize local tomography reconstruction or to separate emission from transmission data. The introduction of TOF also improves the joint estimation of transmission and emission images from emission data only. TOF is also interesting for new applications of PET-like isotopes with low branching ratio for positron fraction. The local nature also reduces the need for fine angular sampling, which makes TOF interesting for limited angle situations like breast PET and online dose imaging in proton or hadron therapy. The aim of this review is to introduce the reader in an educational way into the topic of TOF-PET and to give an overview of the benefits and new opportunities in using this additional information

Drugs for the treatment of central diabetes insipidus: historical background and modern opportunities

Central diabetes insipidus is a severe disease with disturbance of arginine vasopressin secretion, which leads to excretion of large amounts of hypotonic urine. The polyuria-polydipsia syndrome is essential as a clinical presentation and high impact condition. Desmopressin, a synthetic analog of arginine vasopressin, is used to compensate a water-electrolyte balance is available in forms of tablets and intranasal spray. Free drug choice is obligated for proper treatment

Clinical and microbiological evaluation of the efficacy of autoprobiotics in the combination treatment of chronic generalized periodontitis

Combination treatment of patients with inflammatory periodontal diseases may be ineffective due to the variability of periodontal pathogens and the polyetiology of the disease. This disadvantage can be overcome by using highly antagonistic, enzymatic, and immunostimulating drugs, in addition to the main treatment. The objective of this study is to evaluate the efficacy of autoprobiotics clinically and microbiologically in the combination treatment of chronic generalized periodontitis. The presented study involved a survey of 37 patients aged 29 to 64 years with mild chronic generalized periodontitis. The patients were divided into three groups. Group I consisted of patients whose combination treatment included an S. salivarius-based autoprobiotic (subgroup 1 - patients who had their periodontal pockets irrigated with an autoprobiotic, subgroup 2 - patients who used oral baths with autoprobiotic). Group II consisted of patients who used a common S. salivarius-based probiotic in combination treatment (subgroup 1 - patients who had their periodontal pockets irrigated with a probiotic, subgroup 2 - patients who used oral baths with a probiotic). The control group consisted of patients with mild chronic generalized periodontitis, whose combination treatment consisted of professional oral hygiene and correction of individual hygiene. Microbiological examination of the content of periodontal pockets was carried out using PCR screening for periodontal pathogens, such as P. gingivalis, T. denticola, T. forsythia, P. intermedia. Based on the clinical and microbiological results of the study, the efficacy of an autoprobiotic and probiotic based on S. salivarius in the combination treatment of mild chronic generalized periodontitis was demonstrated

Enzyme Replacement Therapy and Hematopoietic Stem Cell Transplantation Results in Patients with Hurler Syndrome: Clinical Cases

Mucopolysaccharidosis type I (MPS I) is the hereditary disease characterized with alpha-L-iduronidase activity decrease and further accumulation of heparan and dermatan sulfate in lysosomes. MPS I is rare autosomal recessive disorder with incidence of 0.5–4 cases on 100.000 live-birth infants. Meantime there two approaches in MPS I treatment: hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). HSCT can be the best option for treatment of patients with severe MPS I (Hurler syndrome). Successful engraftment moderates such clinical signs as obstructive airway diseases, hepatosplenomegaly, cardiovascular system dysfunctions. HSCT prevents cognitive functions decline and other pathologic features of central nervous system. Presented clinical cases show various clinical courses according to age of diagnosis, ERT onset and HSCT implementation

Diagnostic Difficulties of Mucopolysaccharidosis Type I Mild Forms: Clinical Cases

Mucopolysaccharidosis type I mild forms include Scheie syndrome and Hurler-Scheie syndrome that are characterized by slow progression, intact intelligence, and primarily effect on visual organ, musculoskeletal and cardiovascular systems. Early diagnostics, multidisciplinary approach to examination and monitoring, timely management are crucial in maintenance of patients' quality of life, preventing complications development and early disability. The article provides the overview of published data and description of 3 clinical cases with mild course of mucopolysaccharidosis type I

Extracellular Vesicles Derived from Acidified Metastatic Melanoma Cells Stimulate Growth, Migration, and Stemness of Normal Keratinocytes

Metastatic melanoma is a highly malignant tumor. Melanoma cells release extracellular vesicles (EVs), which contribute to the growth, metastasis, and malignancy of neighboring cells by transfer of tumor-promoting miRNAs, mRNA, and proteins. Melanoma microenvironment acidification promotes tumor progression and determines EVs’ properties. We studied the influence of EVs derived from metastatic melanoma cells cultivated at acidic (6.5) and normal (7.4) pH on the morphology and homeostasis of normal keratinocytes. Acidification of metastatic melanoma environment made EVs more prooncogenic with increased expression of prooncogenic mi221 RNA, stemless factor CD133, and pro-migration factor SNAI1, as well as with downregulated antitumor mir7 RNA. Incubation with EVs stimulated growth and migration both of metastatic melanoma cells and keratinocytes and changed the morphology of keratinocytes to stem-like phenotype, which was confirmed by increased expression of the stemness factors KLF and CD133. Activation of the AKT/mTOR and ERK signaling pathways and increased expression of epidermal growth factor receptor EGFR and SNAI1 were detected in keratinocytes upon incubation with EVs. Moreover, EVs reduced the production of different cytokines (IL6, IL10, and IL12) and adhesion factors (sICAM-1, sICAM-3, sPecam-1, and sCD40L) usually secreted by keratinocytes to control melanoma progression. Bioinformatic analysis revealed the correlation between decreased expression of these secreted factors and worse survival prognosis for patients with metastatic melanoma. Altogether, our data mean that metastatic melanoma EVs are important players in the transformation of normal keratinocytes

Central diabetes insipidus after transnasal adenomectomy:trends in development and recovery, clinical and laboratory characteristics

Background: Currently, there is an increase in the incidence of chiasmosellar neoplasms and respective neurosurgical interventions. The postoperative period may be complicated by vasopressin synthesis and secretion disorders. Both the development and abortion of the fluid and electrolyte disorders can be delayed. Due to a tendency for an earlier discharge of the patients, a proportion of the disorders remain unaddressed. There is no data on the evolution and time to regress of transient abnormalities in the published studies with a long-term postoperative follow-up. Aim: To assess the incidence, evolution and regression trends, clinical and laboratory characteristic of postoperative central diabetes insipidus (CDI). Materials and methods: The single center retrospective comparative study included 150 patients who had undergone transnasal adenomectomy for Cushing’s disease, acromegaly, prolactinomas, and hormonally inactive pituitary adenomas. Clinical and laboratory assessments were performed pre- and postoperatively. In the event of CDI, treatment with desmopressin was administered. Ninety six (96) patients aged 20 to 65 years (median age 43 [35; 54] years) were followed for at least 60 months after the procedure. Results: Median time to the onset of permanent CDI (pCDI) was Day 5 [1; 9.5] after surgery, that of transient CDI (tCDI) Day 1 [1; 4.5] with its remission by Day 30 [1.5; 199]. The maximally delayed onset was on Day 86 for the pCDI and Day 61 for tCDI; that to the remission of tCDI, 738 days. At discharge from the hospital, postoperative CDI was present in 34/150 patients (23%; 95% CI 17–30), and in 25/150 of the patients (16%; 95% CI 12–24) the disorder resolved. At 5 to 7 years after surgery, the prevalence of pCDI was 16% (95% CI 10–24), that of tCDI 35% (95% CI 27–45), 49% (95% CI 39–59) of the patients had no abnormalities (respective absolute patient numbers being 15, 34, and 47 of 96 followed for at least 60 months). At Days 1 to 7 after surgery, the patients with pCDI and tCDI had more frequent complaints of dry mouth and thirst than those without the disorder. These complaints were verified by higher 24-hour fluid intake and diuresis at the day of surgery and Days 5 to 7 thereafter, compared to those in the patients without the disorders. At Days 5–7 after surgery, urine sodium and urine specific gravity were significantly lower, as was urine osmolality at all postoperative stages, compared to those in the patients without the disorders. Conclusion: Within 2 years after transnasal adenomectomy, the incidence of postoperative CDI is gradually decreasing (from 23% to 16%). Due to potentially delayed manifestation of water and electrolyte imbalance, it is recommended that these parameters should be monitored at least for 2,5 months after the discharge from hospital. Due to potentially delayed remission (12 months and more), follow-up and monitoring for 1.5 years is reasonable, with periodic assessment of sodium levels, fluid intake and excretion, and attempts to withdraw desmopressin

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients. Among them, 129 patients were then randomized into two groups with similar concomitant medication. Group I (n = 56) received a bolus of cholecalciferol at a dose of 50,000 IU on the first and the eighth days of hospitalization. Patients from Group II (n = 54) did not receive the supplementation. We found significant differences between groups with the preferential increase in serum 25(OH)D level and Δ 25(OH)D in Group I on the ninth day of hospitalization (p p = 0.006); we did not observe other clinical benefits in patients receiving an oral bolus of cholecalciferol. Moreover, in Group I, neutrophil and lymphocyte counts were significantly higher (p = 0.04; p = 0.02), while the C-reactive protein level was significantly lower on the ninth day of hospitalization (p = 0.02). Patients with supplementation of 100,000 IU of cholecalciferol, compared to those without supplementation, showed a decrease in the frequencies of CD38++CD27 transitional and CD27−CD38+ mature naive B cells (p = 0.006 and p = 0.02) and an increase in the level of CD27−CD38− DN B cells (p = 0.02). Thus, the rise in serum 25(OH)D level caused by vitamin D supplementation in vitamin D insufficient and deficient patients may positively affect immune status and hence the course of COVID-19