Search

Cystic changes of the thyroid remain a diagnostic dilemma with regard to malignancy due to insufficient information gained by fine needle aspiration, sonography and routine nuclear medicine procedures. As complementary soluble parameters we measured neopterin and thyroglobin levels in cyst fluids and in serum of 81 patients with disorders of the thyroid. Based on clinical, cytological and histological information, patients were divided into five groups. (I): Serous cysts (n=41), (II): hemorrhagic cysts (N=18), (III): cysts ' with evidence for inflammation clinically or by histology (n= 11), (IV): malignancy in cysts by histology (n = 6), (V): cysts containing "honey" like, brownish fluid of high viscosity (n = 5). Neopterin concentration in cyst fluids vs. serum in group (I) were not different, 8.8± 4.3 nmol/l in vs. 6.67± 3.34 nmol/l. In groups II-V neopterin concentration in cysts were higher than in serum, (II): 21.1 ± 18.7 nmol/l vs. 5.6± 2.56 nmol/l, (III): 30.6± 24.9 nmol/l vs. 6.1 ± 2.9 nmol/l, in (IV): 35± 23.5 vs. 10.98± 7.0 nmol/l and (V): 36.0± 23.9 vs. 5.9± 3.32 nmol/l respectively. In patients with proven benign histology at surgery, neopterin levels in cystic fluid were significantly lower than in cysts harbouring malignancy, 8.5±4.6 vs. 35.4±23.5 (Z=3,17, p=O. 0015). There were no significant differences between groups II, III IV and V regarding neopterin concentrations in cysts. Elevated serum neopterin levels were observed in 2/6 patients with aggressive thyroid cancer (group IV). However, average neopterin concentrations in serum of patients of group IV were not higher than in 15 patients from group I with benign histology (P=O.l). Significantly lower levels of thyroglobin in cyst fluid were found in group V ("honey" cysts) in comparison to all other groups pooled, 2.67± 1.82 f..lg/rnl vs. 6.76± 3.97 f..lg/ml, (Z=2.l5, p=0.031), four of five cysts in group V resolved after fine needle aspiration. We found no correlation between thyroglobin levels in cyst fluid and in serum.

ABSTRACT- In 35 patients on long-term anticonvulsant treatment (7-35 years, x̄ = 19.6 years), various liver enzymes were measured. In 32 cases (91.4%), elevated levels of serum-gamma-glutamyl-transpeptidase (GGT) were found. Liver biopsy was performed in five of 13 patients with GGT levels of >60 U/1 (75-257, x̄ = 123 U/1). Light microscopy showed a minimal steatosis and fine granular appearance of hepatocytes in two cases, and a slight portal fibrosis in one case. Two cases showed an unremarkable histology. Electron microscopy revealed signs of enzyme induction as overall swelling of the smooth endoplasmic reticulum and additionally a dilatation of the rough endoplasmic reticulum in all five specimens. No signs of liver damage or disturbance of liver function could be observed. [ABSTRACT FROM AUTHOR]

Sixty patients with different cardiac diseases and healthy volunteers were given ω-I-123-heptadecanoic acid (HDA) intravenously. Tracer kinetics were followed for 90 min, and tracer elimination curves were obtained regionally. In addition, circumferential washout profiles were evaluated for 26 patients and interpolative as well as constant background subtraction was performed for comparison in selected patients.Rest and stress radionuclide ventriculography allowed formation of a group with normal ventricular function (control group); the remaining patients had an abnormal ventricular function at rest or under stress.Regions of patients in the control group were significantly different (P<0·005) from regions of patients with CHD or CMP with regard to the initial half-life or the component ratio between a fast and a slow component (Ca/Cb). Regions of patients after MI without exercise-induced angina did not differ strikingly from control regions. Circumferential washout analysis showed homogeneous tracer kinetics in healthy subjects, bus some individuals showed increasing regional activity, mainly by late activity uptake of the stomach.Dynamic heart scintigraphy with HDA is an additional nuclear cardiologic tool that makes possible the classification of patients with myocardial disease and abnormal ventricular function already under resting conditions. Initial half-life allows reasonable discrimination between different severely diseased patient groups; expansion of acquisition time to 90 min refines biexponential tracer analysis which, by means of an altered component ratio Ca/Cb, may allow better clinical judgement of the individual patient. Circumferential washout analysis and interpolative background correction lead to a better specificity of examination. [ABSTRACT FROM PUBLISHER]

Introduction: Appropriate pain management indicates the quality of casualty care in trauma. Gender bias in pain management focused so far on the patient. Studies regarding provider gender are scarce and have conflicting results, especially in the military and prehospital settings., Study Objective: The purpose of this study is to investigate the effect of health care providers' gender on pain management approaches among prehospital trauma casualties treated by the Israel Defense Forces (IDF) medical teams., Methods: This retrospective cohort study included all trauma casualties treated by IDF senior providers from 2015-2020. Casualties with a pain score of zero, age under 18 years, or treated with endotracheal intubation were excluded. Groups were divided according to the senior provider's gender: only females, males, or both female and male. A multivariate analysis was performed to assess the odds ratio of receiving an analgesic, depending on the presence of a female senior provider, adjusting for potential confounders. A subgroup analysis was performed for "delta-pain," defined as the difference in pain score during treatment., Results: A total of 976 casualties were included, of whom 835 (85.6%) were male. Mean pain scores (SD) for the female only, male only, and both genders providers were 6.4 (SD = 2.9), 6.4 (SD = 3.0), and 6.9 (SD = 2.8), respectively (P = .257). There was no significant difference between females, males, or both female and male groups in analgesic treatment, overall and per specific agent. This remained true also in the multivariate model. Delta-pain difference between groups was also not significant. Less than two-thirds of casualties in this study were treated for pain among all study groups., Conclusion: This study found no association between IDF Medical Corps providers' gender and pain management in prehospital trauma patients. Further studies regarding disparities in acute pain treatment are advised.

Background: Pain control in trauma is an integral part of treatment in combat casualty care. More soldiers injured on the battlefield need analgesics for pain than life-saving interventions (LSIs). Early treatment of pain improves outcomes after injury, while inadequate treatment leads to higher rates of post-traumatic stress disorder (PTSD)., Objectives: To describe the experience of the Israel Defense Forces (IDF) Medical Corps with prehospital use of analgesia., Methods: All cases documented in the IDF-Trauma Registry between January 1997 and December 2019 were examined. Data collection included analgesia administered, mechanism of injury, wound distribution, and life-saving interventions performed., Results: Of 16,117 patients, 1807 (11.2%) had at least one documented analgesia. Demographics included 91.2% male; median age 21 years. Leading mechanism of injury was penetrating (52.9%). Of injured body regions reported, 46.2% were lower extremity wounds. Most common types of analgesics were morphine (57.2%) and fentanyl (27%). Over the two decades of the study period, types of analgesics given by providers at point of injury (POI) had changed. Fentanyl was introduced in 2013, and by 2019 was given to 39% of patients. Another change was an increase of casualties receiving analgesia from 5-10% until 2010 to 34% by 2019. A total of 824 LSIs were performed on 556 patients (30.8%) receiving analgesia and no adverse events were found in any of the casualties., Conclusions: Most casualties at POI did not receive any analgesics. The most common analgesics administered were opioids. Over time analgesic administration has gained acceptance and become more commonplace on the battlefield.

Rationale: Cutaneous melanoma is the most aggressive and deadliest of all skin malignancies. Complete primary tumor removal augmented by advanced imaging tools and effective post-operative treatment is critical in the prevention of tumor recurrence and future metastases formation. Methods: To meet this challenge, we designed novel polymeric imaging and therapeutic systems, implemented in a two-step theranostic approach. Both are composed of the biocompatible and biodegradable poly(α,L-glutamic acid) (PGA) nanocarrier that facilitates extravasation-dependent tumor targeting delivery. The first system is a novel, fluorescent, Turn-ON diagnostic probe evaluated for the precise excision of the primary tumor during image-guided surgery (IGS). The fluorescence activation of the probe occurs via PGA degradation by tumor-overexpressed cathepsins that leads to the separation of closely-packed, quenched FRET pair. This results in the emission of a strong fluorescence signal enabling the delineation of the tumor boundaries. Second, therapeutic step is aimed to prevent metastases formation with minimal side effects and maximal efficacy. To that end, a targeted treatment containing a BRAF (Dabrafenib - mDBF)/MEK (Selumetinib - SLM) inhibitors combined on one polymeric platform (PGA-SLM-mDBF) was evaluated for its anti-metastatic, preventive activity in combination with immune checkpoint inhibitors (ICPi) αPD1 and αCTLA4. Results: IGS in melanoma-bearing mice led to a high tumor-to-background ratio and reduced tumor recurrence in comparison with mice that underwent surgery under white light (23% versus 33%, respectively). Adjuvant therapy with PGA-SLM-mDBF combined with ICPi, was well-tolerated and resulted in prolonged survival and prevention of peritoneal and brain metastases formation in BRAF-mutated melanoma-bearing mice. Conclusions: The results reveal the great clinical potential of our PGA-based nanosystems as a tool for holistic melanoma treatment management., Competing Interests: Competing Interests: R.S.-F. declares that she is a Board Director at Teva Pharmaceutical Industries and receives research funding from Merck, all for work unrelated to this manuscript. All other authors declare no competing interests., (© The author(s).)

Background: Early pain treatment following injury has been shown to improve long-term outcomes, while untreated pain can facilitate higher posttraumatic stress disorder rates and worsen outcomes. Nonetheless, trauma casualties frequently receive inadequate analgesia. In June 2013, a new clinical practice guideline (CPG) regarding pain management was introduced in the Israel Defense Forces (IDF) Medical Corps, recommending oral transmucosal fentanyl citrate (OTFC) and low-dose intravenous (IV)/intramuscular ketamine. The purpose of this study was to examine trends in prehospital pain management in the IDF., Methods: All cases documented in the IDF trauma registry between 2008 and 2020 were examined. This study compared casualty parameters before and after the introduction of analgesia CPG in 2013. Parameters compared included demographics, injury parameters, treatment modalities, and types of analgesia provided., Result: Overall, 5,653 casualties were included in our study. During the 6 years before the introduction of the CPG, 289 (26.7%) of 1,084 casualties received an analgesic treatment, compared with 1,578 (34.5%) of 4,569 casualties during the 7 years following (p < 0.001). Since its introduction, OTFC was administered to 41.8% of all casualties who received analgesia and became the most used analgesic drug in 2020 (61.1% of casualties receiving analgesia). The rate of IV morphine significantly decreased after 2013 (22.6-16%, p < 0.001)., Conclusion: Pain management has become more common in trauma patients' prehospital care in the IDF in recent years. There has been a significant increase in analgesia administration, with the increased use of OTFC, along with a significant reduction in the use of IV morphine. These results may be attributed to introducing a pain management CPG and implementing OTFC among medical teams. The perception of OTFC as a safe user-friendly analgesic may have contributed to its use by medical providers, increasing analgesia rates overall., Level of Evidence: Therapeutic/care management, level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Targeted therapies against cancer can relieve symptoms and induce remission, however, they often present limited duration of disease control, cause side effects and often induce acquired resistance. Therefore, there is a great motivation to develop a unique delivery system, targeted to the tumor, in which we can combine several active entities, increase the therapeutic index by reducing systemic exposure, and enhance their synergistic activity. To meet these goals, we chose the biocompatible and biodegradable poly(α,L-glutamic acid) (PGA) as a nanocarrier that facilitates extravasation-dependent tumor targeting delivery. The RAS/RAF/MEK/ERK pathway when aberrantly activated in melanoma, can lead to uncontrolled cell proliferation, induced invasion, and reduced apoptosis. Here, we selected two drugs targeting this pathway; a MEK1/2 inhibitor (selumetinib; SLM) and a modified BRAF inhibitor (modified dabrafenib; mDBF), that exhibited synergism in vitro . We synthesized and characterized our nanomedicine of PGA conjugated to SLM and mDBF (PGA-SLM-mDBF). PGA-SLM-mDBF inhibited the proliferation of melanoma cells and decreased their migratory and sprouting abilities without inducing a hemolytic effect. Moreover, the polymer-2-drugs conjugate exhibited superior anti-tumor activity in comparison with the two separate polymer-drug conjugates in vitro and with free drugs in a mouse model of primary melanoma and prolonged survival at a lower dose.

Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined., Methods: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality., Results: This study included 156 patients (median age = 72 years (range = 22-97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0-37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84-0.96) were independent prognostic factors., Conclusions: In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.

Background: Over the last decade, clinical interest to evaluate human 25-hydroxy-vitamin D (25[OH]D) serum levels has increased exponentially. In the present study, four chemiluminescence immunoassays (CLIA), one radioimmunoassy (RIA), and one high performance liquid chromatography (HPLC) method were compared and also with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in view of 25(OH)D serum level determination. Methods: For the method comparison, blood samples from 133 consecutive patients were prospectively collected. All participants gave written informed consent for their blood samples to be used in this study. They came to the Department of Nuclear Medicine of the Central Hospital Steyr (Austria) for osteodensidometric measurement as part of their preventive medical check-up. Pearson's correlation coefficients, Bland-Altman plots, and paired t-tests were calculated. Assay-specific reference ranges were considered using blood samples from persons with normal parathormone, calcium, and total-protein values (n = 97). Results: The highest correlation was between the HPLC and the LC-MS/MS method (r = 0.96). The lowest correlation was between the cobas Vitamin D3 assay (Roche) and any of the evaluated assays (r = 0.46 - 0.63). Bland-Altman plots revealed a big negative mean bias in three assays (cobas Vitamin D3 assay [Roche]: -22.8; DiaSorin LIAISON [25[OH]D total CLIA [Diasorin]: -18.4; Diasorin 25[OH]D125 I RIA [Diasorin]: -23.8 [nmol/L]) and a much smaller positive mean bias in the other assays (ClinRep complete 25[OH]D2/D3 HPLC kit [Recipe]: 2.7; ADVIA Centaur Vitamin D total assay [Siemens]: 8.2; IDS total vitamin D assay [Immunodiagnostic Systems]: 12.1 [nmol/L]) compared to the LC-MS/MS method. Meanwhile, the manufacturer has withdrawn the cobas Vitamin D3 assay from the market. Conclusions: Poor antibody specificity with cross-reactivity to other vitamin D metabolites, incomplete extraction of the 25(OH)D analyte from the vitamin D-binding protein (DBP), and confounding matrix substances such as lipids could be potential reasons for the unacceptable performance of the cobas Vitamin D3 assay (Roche) and also the significant differences in the 25(OH)D determination between various assays. Standardization and harmonization of 25(OH)D measurements are therefore urgently needed. The widespread introduction of well standardized assays in clinical laboratories is the challenge in the next years. (Clin. Lab. 2014;60:1541-1550. DOI: 10.7754/Clin.Lab.2014.131114)

Fatty acids are promptly taken up, metabolised and eliminated by healthy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metabolism. It was the aim of this study to investigate fatty acid metabolism in a rat heart transplant model and to correlate scintigraphic findings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the renal vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-123 jodo-heptadecanoic acid (123J-HDA) with a specific activity of > 2 x 10(17) Bq/ml was scintigraphically measured between days 1 and 11. An increase in the grade of rejection was observed over time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) frames 10-56 were superimposed, time-activity curves generated and monoexponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological examination. The uptake of the tracer identified severe grades of rejection. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did not permit discrimination between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4. This method therefore seems to be a valuable tool for the noninvasive detection of severe acute cardiac allograft rejection. Since fatty acid metabolism is clearly stress-dependent it remains to be seen whether this method allows detection of earlier rejection in loaded hearts.

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.