Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations

We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%), 39% with liver metastases (SDHB +/-: 27% vs 47%), and 32% with lung metastases (SDHB +/-: 37% vs 29%). The most common sites of bone involvement were thoracic spine (80%; SDHB+/-: 83% vs 77%), lumbar spine (78%; SDHB +/-: 78% vs 75%), and pelvic and sacral bones (78%; SDHB +/-: 91% vs 65%, P=0.04). Subjects with SDHB mutation also showed significantly higher involvement of long bones (SDHB +/-: 78% vs 30%, P=0.007) than those without the mutation. The best overall sensitivity in detecting bone metastases demonstrated positron emission tomography (PET) with 6-[(18)F]-fluorodopamine ([(18)F]-FDA; 90%), followed by bone scintigraphy (82%), computed tomography or magnetic resonance imaging (CT/MRI; 78%), 2-[(18)F]-fluoro-2-deoxy-d-glucose ([(18)F]-FDG) PET (76%), and scintigraphy with [(123/131)I]-metaiodobenzylguanidine (71%). In subjects with SDHB mutation, imaging modalities with best sensitivities for detecting bone metastases were CT/MRI (96%), bone scintigraphy (95%), and [(18)F]-FDG PET (92%). In subjects without SDHB mutations, the modality with the best sensitivity for bone metastases was [(18)F]-FDA PET (100%). In conclusion, bone scintigraphy should be used in the staging of patients with malignant pheochromocytoma and paraganglioma, particularly in patients with SDHB mutations. As for PET imaging, [(18)F]-FDG PET is highly recommended in SDHB mutation patients, whereas [(18)F]-FDA PET is recommended in patients without the mutation.     

The Use of Lasers in Disinfection and Cleanliness of Root Canals: a Review

The outcome of root canal treatment is based on efficient disinfection of the root canal system and prevention of reinfection. Current chemomechanical cleaning methods do not always achieve these goals, and insufficient root canal disinfection is the main reason for endodontic failure. Due to high energy content and specific characteristics of laser light, laser treatment has been proposed for cleaning and disinfecting the root canal system. This paper reviews the literature covering the effect of Er:YAG, Er,Cr:YSGG, Nd:YAG and diode laser on the root canal wall in the removal of smear layer and against intracanal bacteria. Recently, the use of laser energy to induce cavitation and acoustic streaming of intracanal irrigants has been investigated. Based on recent literature, it can be concluded that lasers have bactericidal effects. However, they still cannot replace sodium hypochlorite and should be considered as an adjunct to the current chemical root canal disinfection protocols. Certain lasers can help in removing the smear layer and debris and can modify the morphology of the root canal wall. Unfortunately, there have not been enough randomized clinical studies evaluating endodontic treatment outcome following the use of laser.Key words: Disinfection, Root Calan Preparation; Laser Therapy, Low-Level; Smear Layer     

In reply to Swain et al.: Re-evaluation of updated meta-analysis including trials RTOG 1016 and De-ESCALaTE

European Archives of Oto-Rhino-Laryngology -     

Red cell distribution width is a potent prognostic parameter for in-hospital and post-discharge mortality in hospitalized coronavirus disease 2019 patients: a registry-based cohort study on 3941 patients

AimTo investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients.MethodsWe retrospectively analyzed the records of 3941 consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission.ResultsThe median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI; and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index).ConclusionRDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a systemic infectious disease usually presenting with fever and respiratory symptoms (1). Although the most frequent serious manifestation of COVID-19 is pneumonia, the disease has been associated with cardiovascular, neurological, and gastrointestinal symptoms (2). Systemic inflammatory response mediated by high interleukin-6 concentrations induced by SARS-CoV-2 infection is associated with more severe clinical presentation, respiratory deterioration, and death (3,4). The presence of prior chronic comorbidities substantially affects the survival of COVID-19 patients (1).Anisocytosis, ie, unequal red blood cells (RBC) size, is a sensitive marker of distress in erythropoiesis or RBC destruction. It can be induced by various metabolic and inflammatory stimuli, nutrient deficiencies, infections, spleen disorders, and specific drugs interfering with RBC production (5). Anisocytosis can be quantified as a coefficient of variation of mean cell volume termed red blood cell distribution width (RDW), which is obtained by automatic cell counters. Higher RDW levels have recently gained attention as they are uniformly associated with unfavorable presentation and inferior outcomes in many chronic metabolic and malignant diseases (6-12). More severe clinical presentation and higher mortality rates were also found in COVID-19 patients with higher RDW levels (13-16). However, an association of RDW with other clinical outcomes in hospitalized COVID-19 patients, as well as the relationship with increased mortality in the context of other established prognostic scores, are not well defined. Thus, we aimed to investigate clinical and prognostic significance of RDW in a large cohort of hospitalized COVID-19 patients from our institution. We hypothesized that RDW was associated with more severe COVID-19 on admission and higher death rate.     

The development of the subplate and thalamocortical connections in the human foetal brain

The aim of this review is to present clinically relevant data on prenatal development of thalamocortical connections in the human brain. The analysis is based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The connection of thalamocortical axons during the ‘waiting’ period with transient cortical subplate zone and subsequent synaptic engagement in the cortical plate is the main connectivity event in the late foetus and preterm infant. This connectivity is the structural substrate for the endogeneous subplate and sensory‐driven circuitry generating transient electrical phenomena and may represent a transient network in the developmental history of consciousness. Conclusion: Findings presented in this review should be considered in the management of pain in preterm infants, in searching for the vulnerability of the subplate zone in diagnostic procedures using the in vivo MRI and in revealing the developmental origin of cognitive and mental disorders.     

Transvaginal color flow Doppler in the assessment of ovarian and uterine blood flow in infertile women

OBJECTIVE: To measure the flow velocity of the uterine and ovarian arteries through the menstrual cycle to determine there are changes. DESIGN: Serial measurements throughout the menstrual cycle in women attending an infertility clinic, compared with volunteers coming for annual examinations. Transvaginal ultrasound-color flow Doppler was the investigative tool. SETTING: A University Hospital ambulatory care center. PATIENTS: One hundred infertile women compared with 150 women attending the clinic for annual checkups. MAIN OUTCOME MEASURES: Changes in the resistance index of flow velocity waveforms of the uterine and ovarian arteries. RESULTS: Uterine flow velocity has a resistance index of 0.88 +/- 0.04 (2 SE) in the proliferative phase and starts to decrease the day before ovulation. A nadir of 0.84 +/- 0.04 is reached on day 18 and remains at that level for the rest of the cycle. In anovulatory cycles, these changes do not occur. A subgroup of 12 women who lacked end diastolic flow in the uterine arteries during the secretory phase were identified. Eleven of these women were infertile, 8 of whom with primary infertility. Ovarian artery flow velocity is usually detected when the dominant follicle reaches 12 to 15 mm. The resistance index is 0.54 +/- 0.04 and also declines on the day before ovulation. A nadir of 0.44 +/- 0.04 is reached 4 to 5 days later and slowly rises to 0.050 +/- 0.04 before menstruation. CONCLUSIONS: There are changes in the flow velocity patterns of the uterine and ovarian arteries during the normal ovulatory menstrual cycle. Because these changes in flow velocity begin before ovulation, it can be suspected that they may involve angiogenesis as well as hormonal factors. The changes noted in these studies are statistically significant but may be too small to be used as a diagnostic tool in the study of infertility problems.     

Estrogen receptors in human pulp tissue

OBJECTIVE: The aim of this study was to evaluate the expression of estrogen receptor (ER)-alpha in human pulp tissue. STUDY DESIGN: Tissue samples were collected from 51 teeth extracted for orthodontic reasons or from endodontically treated teeth. Immunohistochemical staining was performed with mouse antihuman ER-alpha 1D5 by using the alkaline phosphatase antialkaline phosphatase technique. Immunohistochemical reactivity was semiquantitatively assessed and graded on an intensity scale of 0 to 3. RESULTS: ERs were found in odontoblasts, endothelial cells, and Schwann cells. By means of statistical analysis, ERs were found to be common in odontoblasts (1.3-1.6) and in endothelial cells (1.0-1.4), whereas in Schwann cells they were somewhat rare (0.7-1.1). Difference in expression of ERs was not found among patients in different age groups. With respect to sex, a difference in reactivity was observed in Schwann cells, which showed higher reactivity in female pulps. CONCLUSION: The results of this study confirm the expression of ER-alpha in the human dental pulp.     

Salmonella infection-associated acute rhabdomyolysis. Some pathogenic considerations

Rhabdomyolysis is a syndrome characterized by extended myolysis, elevation of serum aminotransferases and creatine kinase, and myoglobinuria. It is a rare but well-established complication of a spectrum of infectious diseases. Salmonella infections have been connected with this syndrome as well. We present here the case of a 58-year-old female affected by Charcot-Marie-Tooth (CMT) disease, a type of hereditary neuropathy, who presented with acute renal failure and rhabdomyolysis syndrome in the course of Salmonella infantis gastroenteritis. We formed some considerations on the pathogenesis of rhabdomyolysis in this specific setting based on certain experimental works on the Salmonella pathogenic cycle. We concluded that the calcium-dependent mechanism coupled with a predisposing factor might be of major significance in the development of this complication.     

Prevalence in a volunteer population of pelvic cancer detected with transvaginal ultrasound and color flow Doppler.

Our objective was to find the prevalence of non-symptomatic endometrial and ovarian neoplasms in a volunteer population of women, aged 40 and over. We offered a free volunteer screening program to asymptomatic women for a study using transvaginal ultrasound and color flow Doppler for the detection of pelvic cancer. In the first 2 years, 2117 women were examined, 51.3% post-menopausal. An ovarian cyst was defined as having a maximum diameter of more than 2.4 cm. Color flow was used to identify blood vessels feeding pelvic organs and adnexal enlargements. An abnormal Doppler flow velocity for the ovary was defined as a resistance index of less than 0.41. Ovarian cysts of less than 5 cm with normal Doppler indices were followed up in 6 months to 1 year. An adnexal morphology score was created to quantify the usefulness of this parameter, particularly in postmenopausal women. Indications for surgery were pre-defined as a persistent ovarian cyst of more than 5 cm, a persistent suspicious Doppler and a total endometrial thickness of greater than 0.59 cm in postmenopausal women not taking hormones.A total of 202 women (9.5%) had ovarian cysts. Fourteen women were operated upon because of size criteria, one because of family history and three for persistent abnormal flow. By Doppler study, 15 cysts were predicted to be benign and histology was confirmatory. There were two false positives and one true positive, a stage Ib ovarian cancer. There were no false negatives, although a stage I endometrioid cancer of the ovary was detected 8 months after a negative scan. In those cases in which follow-up data were available, 56% of the cysts regressed in premenopausal women. In postmenopausal women, 28% regressed. Twenty of 1086 postmenopausal women had endometrial biopsies. Three had endometrial cancer, two stage I and one stage IIA. Five had atypical or adenomatous hyperplasia, and seven had benign polyps.So many women have small asymptomatic cysts of the ovary that a major reorientation of physicians' attitudes towards the ovary will have to be introduced to adapt to this new information. In this population, the prevalence of benign epithelial ovarian neoplasms was 7/1000, and of malignancy was 05/1000. In postmenopausal women, the prevalence rate for endometrial cancer was 5/1000, with 5/1000 hyperplasias and 7/1000 benign polyps. When endometrial and ovarian cancer screening are combined, the yield is comparable to that seen in breast and cervical cancer screening.