Epidemiological and pathological characteristics of spinal metastases from gastrointestinal cancers - a series of 40 cases.

Spinal metastases from gastrointestinal (GI) cancer are rare and as a result there are only case reports or small series in the literature. The aim of our work was to identify the demographic aspects, the location, and the histopathological aspects of spinal metastases from GI cancers diagnosed and treated in a reference Hospital in Romania over a period of nine years, and comparing the data obtained with those from the recent literature. This is a retrospective case series study on spinal metastases from GI cancers, developed in patients older than 18 years that were surgically treated between January 2013 and December 2021 within three Neurosurgery Clinics from Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, which is a tertiary Hospital in Romania regarding the surgical treatment of spinal metastases. We included in our study the patient's demographic data (age and gender), clinical data (location of spinal metastases), radiological investigations and pathological features of the lesions. Regarding the immunohistochemical stainings, the following antibodies were used: anti-cytokeratin (CK)7, anti-CK20, anti-CK19, anti-caudal-type homeobox 2 (CDX2), anti-human epidermal growth factor receptor 2 (HER2), and anti-Ki67. Our series included 40 adult patients (≥18 years old) with a male:female ratio of 3:1, in favor of male patients. The mean age of all patients was 66.42 years. The primary sites of spinal metastases from GI cancers were from all segments of the GI system: the most frequent, however, was from the colorectal level (40%) and the least from the oral cavity level (2.5%). The most common site of spinal metastases from GI cancer was predominantly lumbar region (47.5%), and the most frequent histological type was adenocarcinoma (57.5%), followed by hepatocellular carcinoma (27.5%), pancreatic ductal carcinoma (5%) and squamous cell carcinoma (2.5%). Our results have important clinical implications because they suggest that there are certain subsets of patients with certain types of GI cancers that cause metastases in certain regions of the spine.

Beyond the Acute Phase: Long-Term Impact of COVID-19 on Functional Capacity and Prothrombotic Risk-A Pilot Study.

Background and Objectives: Assessment of the prothrombotic, proinflammatory, and functional status of a cohort of COVID-19 patients at least two years after the acute infection to identify parameters with potential therapeutic and prognostic value. Materials and Methods: We conducted a retrospective, descriptive study that included 117 consecutive patients admitted to Iasi Pulmonary Rehabilitation Clinic for reassessment and a rehabilitation program at least two years after a COVID-19 infection. The cohort was divided into two groups based on the presence (n = 49) or absence (n = 68) of pulmonary fibrosis, documented through high-resolution computer tomography. Results: The cohort comprises 117 patients, 69.23% females, with a mean age of 65.74 ± 10.19 years and abnormal body mass index (31.42 ± 5.71 kg/m2). Patients with pulmonary fibrosis have significantly higher levels of C-reactive protein (CRP) (p < 0.05), WBC (7.45 ± 7.86/mm3 vs. 9.18 ± 17.24/mm3, p = 0.053), neutrophils (4.68 ± 7.88/mm3 vs. 9.07 ± 17.44/mm3, p < 0.05), mean platelet volume (MPV) (7.22 ± 0.93 vs. 10.25 ± 0.86 fL, p < 0.05), lactate dehydrogenase (p < 0.05), and D-dimers (p < 0.05), but not ferritin (p = 0.470), reflecting the chronic proinflammatory and prothrombotic status. Additionally, patients with associated pulmonary fibrosis had a higher mean heart rate (p < 0.05) and corrected QT interval (p < 0.05). D-dimers were strongly and negatively correlated with diffusion capacity corrected for hemoglobin (DLCO corr), and ROC analysis showed that the persistence of high D-dimers values is a predictor for low DLCO values (ROC analysis: area under the curve of 0.772, p < 0.001). The results of pulmonary function tests (spirometry, body plethysmography) and the 6-minute walk test demonstrated no significant difference between groups, without notable impairment within either group. Conclusions: Patients with COVID-19-related pulmonary fibrosis have a persistent long-term proinflammatory, prothrombotic status, despite the functional recovery. The persistence of elevated D-dimer levels could emerge as a predictive factor associated with impaired DLCO.

Anatomical study of circle of Willis on fresh autopsied brains. A study of a Romanian population.

Because the circle of Willis (CoW) supplies blood to the brain in case of occlusion of one of the cerebral arteries, identification of any change in its classical shape could be useful in the assessment of cerebrovascular morbidity. The purpose of our research was to study the anatomical variants of CoW identified on fresh brains obtained at the clinical autopsies of adult deceased patients belonging to a specific population (Northeastern region of Romania), as no data are available for Romania population up to date. The study group included consecutive patients who died in Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, due to medical causes between January 1, 2014 and June 30, 2016, to whom a clinical autopsy was performed. From a total of 96 circles of Willis, 29.17% presented an atypical morphology. We identified eight types of anatomical variants, which affected simultaneously both the posterior and the anterior parts of CoW in 46.42% of cases. The most frequent anatomical variants were hypoplasia (20.91%), followed by the absence of an artery (3.06%), and partially fetal type artery (2.04%). 67.86% of atypical CoW exhibited more than one anatomical variant of an artery in one circle. We identified nine of the 23 morphological patterns that were published to date, and also nine new types. Our research proved that in the population living in the Northeastern part of Romania the anatomical variations of circles of Willis are very polymorphic, with particular morphological aspects.

Acute and Long-Term Consequences of COVID-19 on Arterial Stiffness-A Narrative Review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global coronavirus (COVID-19) pandemic. Although initially viewed as an acute respiratory illness, COVID-19 is clearly a complex multisystemic disease with extensive cardiovascular involvement. Emerging evidence shows that the endothelium plays multiple roles in COVID-19 physiopathology, as both a target organ that can be directly infected by SARS-CoV-2 and a mediator in the subsequent inflammatory and thrombotic cascades. Arterial stiffness is an established marker of cardiovascular disease. The scope of this review is to summarize available data on the acute and long-term consequences of COVID-19 on vascular function. COVID-19 causes early vascular aging and arterial stiffness. Fast, noninvasive bedside assessment of arterial stiffness could optimize risk stratification in acute COVID-19, allowing for early escalation of treatment. Vascular physiology remains impaired at least 12 months after infection with SARS-CoV-2, even in otherwise healthy adults. This raises concerns regarding the extent of arterial remodeling in patients with preexisting vascular disease and the potential development of a persistent, chronic COVID-19 vasculopathy. Long-term follow up on larger cohorts is required to investigate the reversibility of COVID-19-induced vascular changes and their associated prognostic implications.

Arterial Stiffness Assessment Using the Arteriograph in Patients with Moderate-Severe OSA and Metabolic Syndrome-A Pilot Study.

BACKGROUND: Both obstructive sleep apnea (OSA) and metabolic syndrome (MS) promote arterial stiffening. As a basis for this study, we presumed that arterial stiffness could be assessed using the Arteriograph (TensioMed, Budapest, Hungary) to detect early modifications induced by continuous positive airway therapy (CPAP) in reversing this detrimental vascular remodeling. Arterial stiffness is increasingly acknowledged as a major cardiovascular risk factor and a marker of subclinical hypertension-mediated organ damage. The aim of this pilot study was to evaluate the arterial stiffness changes in patients with moderate-severe OSA and MS after short-term CPAP use. METHODS: We performed a prospective study that included patients with moderate-severe OSA and MS who had not undergone previous CPAP therapy. All subjects underwent clinical examination and arterial stiffness assessment using the oscillometric technique with Arteriograph (TensioMed, Budapest, Hungary) detection before and after 8-week CPAP therapy. RESULTS: 39 patients with moderate-severe OSA were included. Eight weeks of CPAP therapy significantly improved central systolic blood pressure (Δ = -11.4 mmHg, p = 0.009), aortic pulse wave velocity (aoPWV: Δ = -0.66 m/s, p = 0.03), and aortic augmentation index (aoAix: Δ = -8.25%, p = 0.01) only in patients who used the device for a minimum of 4 h/night (n = 20). CONCLUSIONS: Arterial stiffness was improved only among CPAP adherent patients and could be detected using the Arteriograph (TensioMed, Budapest, Hungary), which involves a noninvasive procedure that is easy to implement for the clinical evaluation of arterial stiffness.

Obstructing Sleep Apnea in Children with Genetic Disorders-A Special Need for Early Multidisciplinary Diagnosis and Treatment.

Background-Children with genetic disorders have multiple anatomical and physiological conditions that predispose them to obstructive sleep apnea syndrome (OSAS). They should have priority access to polysomnography (PSG) before establishing their therapeutic protocol. We analyzed the prevalence and the severity of OSAS in a particular group of children with genetic disorders and strengthened their need for a multidisciplinary diagnosis and adapted management. Methods-The retrospective analysis included children with genetic impairments and sleep disturbances that were referred for polysomnography. We collected respiratory parameters from sleep studies: apnea-hypopnea index (AHI), SatO2 nadir, end-tidal CO2, and transcutaneous CO2. Subsequent management included non-invasive ventilation (NIV) or otorhinolaryngological (ENT) surgery of the upper airway. Results-We identified 108 patients with neuromuscular disorders or multiple congenital anomalies. OSAS was present in 87 patients (80.5%), 3 of whom received CPAP, 32 needed another form of NIV during sleep, and 15 patients were referred for ENT surgery. The post-therapeutic follow-up PSG parameters confirmed the success of the treatment. Conclusions-The upper airway obstruction diagnostics and management for children with complex genetic diseases need a multidisciplinary approach. Early detection and treatment of sleep-disordered breathing in children with genetic disorders is a priority for improving their quality of life.

Saccular function evolution related to cochlear implantation in hearing impaired children.

Vestibular sensorial input is essential for psychomotor development of the very small children. In consequence, possible vestibular impairment induced by cochlear implantation in deaf children could affect the balance and walking learning process. Some of cochlear implanted children can present congenital vestibular deficit. The anatomical and embryological relation between auditory and vestibular system explains why congenital neurosensorial hearing loss may associate vestibular impairment. The cochlear implant surgery presents a vestibular lesion risk. Bilateral vestibulopathy, as it appears in early childhood, has a poor prognosis for the psychomotor and cognitive development. Even probably rare, bilateral vestibulopathy induced by simultaneous bilateral cochlear implantation can delay the acquisition of motor skills. This pathology can be avoided by an appropriate surgical indication related to the vestibular preoperative status. This study reports the vestibular saccular functional modifications after the cochlear implantation in children. The cervical vestibular evoked myogenic potentials (cVEMPs) were performed in children before and after the cochlear implantation. Since previous studies report different vestibular impairment related to the portelectrode insertion approach, another objective of our study was to assess the saccular postoperative status depending of the insertion by cochleostomy (CO) or through the round window (RW). We performed cVEMPs for 80 patients (135 cochlear implanted ears) before and after cochlear implantation. We have detected preoperative saccular areflexia in 33 (24.4%) ears. In the group of 102 (75.6%) ears with preoperative normal saccular function, 72 (70.6%) ears preserved the cVEMP response after the surgery, while in 30 (29.4%) ears the cVEMP response was lost. Reporting our findings to the portelectrode insertion method, we found normal saccular function in 73.3% of the cochlear implanted ears by RW surgical approach and in 68.42% ears by CO approach. These results suggest that the RW portelectrode insertion is the recommended strategy in order to avoid the saccular vestibular impairment.

Cavernous liver hemangioma complicated with spontaneous intratumoral hemorrhage: a case report and literature review.

Hemangiomas, the most common benign tumors of the liver, have a prevalence of approximately 20% and are more frequent in women. According to previous studies, the size and location of the tumor are correlated with the appearance of symptoms and complications. Cases of hemangiomas complicated by spontaneous intratumoral hemorrhage have been rarely reported in the literature. Here, we report the case of a 70-year-old woman admitted for persistent upper abdominal pain. The patient showed signs of anemia, inflammatory markers and a transient increase in creatinine levels, which were corrected by conservative treatment. Our patient denied the previous use of estrogen derivatives, smoking or alcohol consumption. Native computed tomography identified a liver mass measuring 73×63 mm, located in segment IV and bulging out of the anterior contour of the liver. The mass was surgically removed by hepatic segmentectomy, and histopathological examination identified a cavernous hemangioma complicated by intratumoral hemorrhage. The postoperative outcome was favorable. After a literature review, we identified 19 other cases of hepatic cavernous hemangioma complicated by intratumoral hemorrhage reported worldwide.

Vestibular sensory functional status of cochlear implanted ears versus non-implanted ears in bilateral profound deaf adults.

Patients with hearing loss who underwent cochlear implantation can present symptomatic or asymptomatic vestibular damages earlier or later after the surgery. The vestibular permanent lesions could be acute, produced by surgical trauma or could be progressive due to local morphological changes made by the presence of the portelectrode in the inner ear (fibrosis related, ossification, basilar membrane distortion, endolymphatic hydrops). Besides histopathological findings in inner ear of cochlear implanted patients, the vestibular permanent damages could be found by assessment of clinical vestibular status. This study reports the sensorial vestibular functional findings for adults in cochlear implanted ears related to the electrode insertion type (cochleostomy or round window approach) and comparing to non-implanted deaf ears. A total of 20 adult patients with 32 cochlear implanted ears (12 patients with binaural cochlear implant and eight with monoaural) were selected for postoperatory vestibular examination by cervical and ocular vestibular myogenic potentials and vestibular caloric tests. The same tests were made for a control group of 22 non-implanted deaf ears. Functional testing results were reported related to the electrode insertion approach. For the cochleostomy group, we found different deficits: in 40% for saccular function, 44% for utricular function, and 12% horizontal canal dysfunction. In round window group, the deficit was present in 14.29% for saccular function, 28.57% for utricular function, and 28.58% for horizontal canal. In 46.88% of implanted ears, the vestibular function was completely preserved on all tested sensors. In conclusion, the vestibular functional status after inner ear surgery presents sensorial damages in 53.12% ears compare with the vestibular dysfunction existing in 50% of deaf non-operated ears. Round window insertion allows for better conservation of the vestibular function.

Distinct activation of the sympathetic adreno-medullar system and hypothalamus pituitary adrenal axis following the caloric vestibular test in healthy subjects.

INTRODUCTION: The vestibular acute stress induces reversible alert-like reactions that involve the sympathetic adrenal-medullar system and hypothalamic-pituitary-adrenal axis responses. The present study aimed to evaluate salivary α-amylase and salivary cortisol production in relation with cardiovascular reactivity induced by acute stress in healthy subjects. MATERIAL AND METHODS: Forty-eight young healthy male volunteers were examined under basal conditions and at various times after reaching the maximal nystagmic reaction following air caloric vestibular test. Heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were recorded at the same time as measurement of the salivary α-amylase and salivary cortisol. At the end of the caloric vestibular test session, perceived stress scale questionnaires were administered to measure the self-perceived stress impact induced by the task, and individual scores were compared with those measured on the enrollment day. RESULTS: Following caloric vestibular test-evoked vertigo, salivary α-amylase and cortisol showed distinct trends in their production after acute stress: Student's t-test was used to compare the α-amylase vs cortisol slopes of the respective interpolated regression lines, and the difference was significant (t = -3.283; p<0.001); an increase in salivary cortisol production corresponded with a decrease in the salivary α-amylase concentration. In addition, salivary biomarker modifications were associated with consistent changes in the heart rate, systolic blood pressure and mean arterial pressure. CONCLUSIONS: Using the air caloric vestibular test task as a stressor, the present study demonstrated a connection between the acute hormonal stress response to vestibular stimulation and cardiovascular output. However, further research is needed before we can define the potential importance of the consistent cardiovascular activity changes evoked by vestibular stimulation and the possible functional consequences for cardiovascular regulation and orthostatic tolerance in humans.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study / Desequilíbrio na proporção salivar diurna de testosterona/cortisol em homens com apneia obstrutiva do sono grave: um estudo observacional

ABSTRACT INTRODUCTION: The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE: The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS: Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION: The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

Resumo Introdução: A relação complexa entre os distúrbios do sono e os hormônios pode levar a alterações na produção de cortisol e testosterona em pacientes com Apneia obstrutiva do sono (AOS). Objetivo: O objetivo deste estudo foi determinar as curvas diurnas de testosterona e cortisol livres na saliva e sua proporção (razão T/C). Método: Dez indivíduos recém-diagnosticados com AOS com base na avaliação por polissonografia noturna e sonolência diurna excessiva e sete controles pareados foram recrutados, consecutivamente. Cortisol e testosterona foram medidos em amostras de saliva coletadas ao acordar, ao meio-dia e à noite. A avaliação psicométrica dos distúrbios de ansiedade/depressão e função sexual mencionados foi realizada para detectar a presença de comorbidades neuropsicológicas. Resultados: O achado principal foi que os indivíduos com AOS apresentam hipocortisolismo ao acordar e uma redução significante na concentração de testosterona à noite, em comparação com o grupo controle, que manteve a variação fisiológica diurna de testosterona e cortisol com concentrações hormonais mais elevadas pela manhã e concentrações mais baixas durante a noite. O uso de dados de várias mensurações diurnas, em vez de uma única mensuração, permitiu detectar as alterações na razão T/C de sinais opostos no início e no final do dia: os indivíduos com AOS apresentaram razão T/C maior que os controles na parte da manhã, enquanto que a razão T/C foi significantemente inferior à dos controles durante a noite. Conclusão: Os desequilíbrios no balanço anabólico-catabólico diurno sugerem que a AOS está associada a uma desregulação dos eixos hipotálamo-hipófise-adrenal e hipotálamo-hipófise-gonadal, potencialmente a causa subjacente de algumas das comorbidades neuropsicológicas observadas em pacientes com AOS.

No definitive evidence for a connection between autoimmune thyroid diseases and stress in women.

The purpose of this literature review was to examine the available clinical studies performed during the last 15 years to identify if there is a causal relationship between the onset and course of autoimmune thyroid diseases (AITDs) and the hypothalamic-pituitary-adrenal (HPA) axis/sympathetic-adrenomedullary system (SAM) (dys)function in women. Using the PubMed, Web of Science and Scopus databases, a comprehensive search was performed, and 14 articles were finally identified. The majority of selected studies suggested a causal connection between Graves' Disease (GD) and stress, as well as between Hashimoto Thyroiditis (HT), with its variant postpartum thyroiditis, and stress. However, due to heterogeneity in the protocols, mainly based on the theoretical side effects of stress on the immune-neuroendocrine system, and the different modalities used to establish the impact of stress on individuals, no definitive conclusions could be reached to explain the mechanisms by which stress contributes to the onset of AITDs in women and to determine whether stress management could help in modifying the course of AITDs.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study.

INTRODUCTION: The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE: The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS: Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION: The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

Salivary biomarkers of obstructive sleep apnea syndrome in children.

OBJECTIVES: The present pilot study was performed to evaluate the HPA axis and ANS activity by measuring salivary cortisol and α-amylase diurnal trajectory and production, respectively, in mild or moderate-to-severe (MS) OSA-affected, but otherwise healthy, children. Moreover, a correlative analysis was performed between the salivary biomarker concentrations and the PSG variables characterizing the OSA severity. METHODS: We studied 27 consecutive OSA patients (13 mild OSA; 14 MS OSA) and seven healthy children who were enrolled as controls by collecting salivary samples and measuring cortisol and α-amylase levels using enzyme-linked bioassays. RESULTS: Compared with controls, both mild and MS OSA children showed: (1) increased salivary cortisol diurnal production, (2) maintenance of the physiological circadian activity of the HPA axis, and (3) no changes in α-amylase diurnal trajectory and production. In addition, morning salivary cortisol concentrations was negatively associated with the disease severity in the MS OSA group. CONCLUSIONS: OSA is associated with dysregulation of the HPA axis activity in children, the latter potentially underlying some of the adverse consequences of the disease.

Restoring the salivary cortisol awakening response through nasal continuous positive airway pressure therapy in obstructive sleep apnea.

Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.