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Gallbladder carcinoma is the most common biliary tract tumor and the fifth most common gastrointestinal tract cancer .The prognosis of gallbladder carcinoma is poor and less than 5% of the patients are still alive five years postoperatively.1 Gallbladder specimens were obtained during surgical operations performed in eleven patients for resection of a gallbladder carcinoma, and during five autopsies (control cases selected among patients who died from for other causes, excluding those suffering from biliary or hepatic diseases). Immunohistochemical characterization and distribution of neurotrophins, with their respective receptors, were analyzed. The actual role played by these neurotrophic factors in the general regulation, vascular permeability, algic responsiveness, release of locally active substances and potential tumorigenesis in the gallbladder and biliary ducts compartment remains controversial. Our study revealed an increased immunohistochemical expression of NGF and TrKA in the epithelium and in the epithelial glands of the gallbladder carcinoma together with an evident immunoreactivity for BDNF in the same neoplastic areas. An evident immunoreactivity for NGF, TrKA and BDNF was observed in control specimens of gallbladder obtained during autopsies, whereas a weak or quite absent immunoreactivity was observed in the same specimens for NT4, TrKC and p75. On the contrary an appreciable immunoreactivity for p75 was observed in the specimens harvested from patients with gallbladder carcinoma. We also investigated the expression of some known tumor markers such as MIB-1 (anti Ki-67), CD34 and CA15-3, to identify a possible correlation between the expression of these molecular factors and the prognosis of gallbladder carcinoma. They resulted highly expressed in the stroma (CD34 and CA 15-3) and in the epithelium/epithelial glands (MIB-1) of the neoplastic areas and appeared to be almost absent in the control cases, suggesting that these markers, taken together, could be adopted as a panel of prognostic factors in the evaluation of the gallbladder carcinoma.

Fluids are given with the purpose of increasing cardiac output (CO), but approximately only 50% of critically ill patients are fluid responders. Since the effect of a fluid bolus is time-sensitive, it diminuish within few hours, following the initial fluid resuscitation. Several functional hemodynamic tests (FHTs), consisting of maneuvers affecting heart-lung interactions, have been conceived to discriminate fluid responders from non-responders. Three main variables affect the reliability of FHTs in predicting fluid responsiveness: (1) tidal volume; (2) spontaneous breathing activity; (3) cardiac arrythmias. Most FTHs have been validated in sedated or even paralyzed ICU patients, since, historically, controlled mechanical ventilation with high tidal volumes was the preferred mode of ventilatory support. The transition to contemporary methods of invasive mechanical ventilation with spontaneous breathing activity impacts heart-lung interactions by modifying intrathoracic pressure, tidal volumes and transvascular pressure in lung capillaries. These alterations and the heterogeneity in respiratory mechanics (that is present both in healthy and injured lungs) subsequently influence venous return and cardiac output. Cardiac arrythmias are frequently present in critically ill patients, especially atrial fibrillation, and intuitively impact on FHTs. This is due to the random CO fluctuations. Finally, the presence of continuous CO monitoring in ICU patients is not standard and the assessment of fluid responsiveness with surrogate methods is clinically useful, but also challenging. In this review we provide an algorithm for the use of FHTs in different subgroups of ICU patients, according to ventilatory setting, cardiac rhythm and the availability of continuous hemodynamic monitoring., Competing Interests: Declarations. Conflict of interest: None declared. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose of Review: The purpose of this article is to systematically review and critically assess the existing data regarding the use of transpulmonary thermodilution (TPTD), by providing a detailed description of technical aspects of TPTD techniques, appraising the use of TPTD-derived parameters in specific clinical settings, and exploring the limits of this technique., Recent Findings: The aim of hemodynamic monitoring is to optimize cardiac output ( CO ) and therefore improve oxygen delivery to the tissues. Hemodynamic monitoring plays a fundamental role in the management of acutely ill patients. TPTD is a reliable, multiparametric, advanced cardiopulmonary monitoring technique providing not only hemodynamic parameters related to cardiac function, but also to the redistribution of the extravascular water in the thorax. The hemodynamic monitors available in the market usually couple the intermittent measurement of the CO by TPTD with the arterial pulse contour analysis, offering automatic calibration of continuous CO and an accurate assessment of cardiac preload and fluid responsiveness., Summary: The TPTD is an invasive but well tolerated, multiparametric, advanced cardiopulmonary monitoring technique, allowing a comprehensive assessment of cardiopulmonary condition. Beyond the CO estimation, TPTD provides several indices that help answering questions that clinicians ask themselves during hemodynamic management. TPTD-guided algorithm obtained by pulse contour analysis may be useful to optimize fluid resuscitation by titrating fluid therapy according to functional hemodynamic monitoring and to define safety criteria to avoid fluid overload by following the changes in the extravascular lung water (EVLW) and pulmonary vascular permeability index (PVPI)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: During the coronavirus disease 2019 (COVID-19) outbreak, a critical care outreach team was implemented in our hospital to guarantee multidisciplinary patient assessment at admission and prompt ICU support in medical wards. In this paper, we report the activity plan results and describe the baseline characteristics of the referred subjects., Methods: We retrospectively evaluated data from 125 subjects referred to the critical care outreach team from March 22 to April 22, 2020. We considered subjects with a ceiling of care decision, with those deemed eligible assigned to level 3 care (ward subgroup), and those deemed ineligible admitted to the ICU (ICU subgroup). Quality indicators of the outreach team plan delivery included number of cardiac arrest calls, number of intubations in level 2 areas, and ineffective palliative support., Results: We enrolled 125 consecutive adult subjects with a confirmed diagnosis of COVID-19. We did not report any emergency endotracheal intubations in the clinical ward. In the care ceiling subgroup, we had 2 (3.3%) emergency calls for cardiac arrest, whereas signs of ineffective palliative support were reported in 5 subjects (12.5%). Noninvasive forms of respiratory assistance were delivered to 40.0% of subjects in the ward subgroup (median 3 d [interquartile range (IQR) 2-5]), to 45.9% of subjects in the care ceiling subgroup (median 5 d [IQR 3-7]), and to 64.7% of subjects in the ICU subgroup (median 2.5 d [IQR 1-3]). Thirty of the 31 ward subjects (96.7%), 26 of the 34 ICU subjects, (76.4%), and 19 of the 61 ceiling of care subjects (31.1%) were discharged., Conclusions: In the context of a hospital and ICU surge, a multidisciplinary daily plan supported by a dedicated critical care outreach team was associated with a low rate of cardiac arrest calls, no emergency intubations in the ward, and appropriate palliative care support for subjects with a ceiling of care decision., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as from the area in which the meningioma had its dural attachment. Immunohistochemical characterization and distribution of neurotrophins, with their receptors, were analyzed. The concrete role played by these neurotrophic factors in general regulation, vascular permeability, algic responsivity and release of locally active substances in the human dura mater is still controversial. Our study revealed a general structural alteration of dural tissue due to the invasivity of meningiomatous lesions, together with an improved expression of brain derived neurotrophic factor (BDNF) in highly proliferating neoplastic cells and an evident production of nerve growth factor (NGF) in inflammatory cells, suggesting that BDNF has a role in supporting the proliferation rate of neoplastic cells, while NGF is involved in the activation of a chronic inflammatory response in neoplastic areas.

Lymphoid organs are supplied by many nerve endings associated with different kinds of cells and macrophages. The role of this innervation on the release of locally active molecules is still unclear. Lingual tonsils belong to Waldeyer's Ring, in close association with palatine tonsils and nasopharyngeal (adenoids) tonsils, thus constituting part of NALT (nasal-associated lymphoid tissue) together with the tubal tonsils and lateral pharyngeal bands. In this study, we focused our attention on the expression of some neurotrophins (NTs) and their high- and low-affinity receptors in human lingual tonsils. Light immunohistochemistry showed that human tonsillar samples were generally positive for all the NTs investigated (NGF, BDNF, NT-3, NT-4) and their receptors (TrKA, TrKB, TrKC and p75) with some different expression levels. NGF and TrKC were strongly expressed in macrophages, but weakly in lymphocytes. However, BDNF and TrKB was highly expressed in lymphocytes and weaker in macrophages. The low-affinity receptor for NGF, p75, was mainly moderately expressed in the analysed samples. These results suggest the presence of a pattern of neurotrophin innervation in the human lingual tonsil which may play a role in sustaining inflammatory conditions and in modulating a close interaction between the nervous system and the different immune cellular subtypes.

Compared to the normal epidermal epithelium, cholesteatomas have altered growth properties characterized by the excessive growth of keratinocytes leading to mucosal destruction. Either congenital or acquired, these lesions, which grow in the middle ear space, the petrous apex or the mastoid of temporal bones, are mostly considered benign skin tumoral lesions. However, many questions remain concerning their pathophysiology. Numerous studies have been proposed to identify those cholesteatoma lesions at risk of recurrence, a possible event that may cause hearing loss. We examined patients with petrous apex or mastoid cholesteatoma in order to analyze the expression of various neurotransmitters, neurotrophins and their receptors and the Ki-67 antigen for identification of a possible relationship between clinical outcome and histopathological behaviour in terms of the proliferative activity of cholesteatomas. Expression of the analyzed molecules was studied using immunohistochemical methods in seven adult patients with petrous apex cholesteatoma who underwent surgical removal of the lesion. Our results, in accordance with published data, confirm that Molecular Immunology Borstel-1 (MIB-1) and certain neurotransmitters could be useful in the prognostic evaluation of the risk of recurrence of aggressive forms of cholesteatoma.