Review

Authors: Sang Duk Hong

Endoscopic skull-base surgery (ESBS) is a rapidly growing surgical area that involves collaboration of otolaryngology-head and neck surgeons and neurosurgeons. Various tumor pathologies and extents have been successfully treated with ESBS, and diverse reconstruction methods have been adopted since its introduction. The optimal reconstructive strategy should be based on heterogeneous surgical situations and tumor extent. Nevertheless, there are few current guidelines for selecting reconstructive methods. Therefore, we review diverse options for endoscopic skull-base reconstruction.

PubMed: 39665056
DOI: 10.18787/jr.2021.00401

Review

Authors: Debasish Basak, David Gamez, Subrata Deb...

Sodium-glucose cotransporter 2 (SGLT2) serves as a critical glucose transporter that has been reported to be overexpressed in cancer models, followed by increased glucose uptake in both mice and humans. Inhibition of its expression can robustly thwart tumor development in vitro and in vivo. SGLT2 inhibitors are a comparatively new class of antidiabetic drugs that have demonstrated anticancer effects in several malignancies, including breast, liver, pancreatic, thyroid, prostate, and lung cancers. This review aims to assess the extent of SGLT involvement in different cancer cell lines and discuss the pharmacology, mechanisms of action, and potential applications of SGLT2 inhibitors to reduce tumorigenesis and its progression. Although these agents display a common mechanism of action, they exhibit distinct affinity towards the SGLT type 2 transporter compared to the SGLT type 1 transporter and varying extents of bioavailability and half-lives. While suppression of glucose uptake has been attributed to their primary mode of antidiabetic action, SGLT2 inhibitors have demonstrated several mechanistic ways to combat cancer, including mitochondrial membrane instability, suppression of β-catenin, and PI3K-Akt pathways, increase in cell cycle arrest and apoptosis, and downregulation of oxidative phosphorylation. Growing evidence and ongoing clinical trials suggest a potential benefit of combination therapy using an SGLT2 inhibitor with the standard chemotherapeutic regimen. Nevertheless, further experimental and clinical evidence is required to characterize the expression and role of SGLTs in different cancer types, the activity of different SGLT subtypes, and their role in tumor development and progression.

PubMed: 37509506
DOI: 10.3390/biomedicines11071867

Review

Authors: A Cap, B J Hunt

Over the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are bleeding when they come in to the emergency department have an established coagulopathy before the haemodilution effects of fluid resuscitation. This has led to the use of new terminology: acute traumatic coagulopathy, acute coagulopathy of trauma shock or trauma-induced coagulopathy. The recognition of acute traumatic coagulopathy is important, because we now understand that its presence is a prognostic indicator, as it is associated with poor clinical outcome. This has driven a change in clinical management, so that the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with coagulopathy, has changed to haemostatic resuscitation as early as possible. While there is as yet no universally accepted assay or definition, many experts use prolongation of the prothrombin time to indicate that there is, indeed, a coagulopathy. Hypoxia, acidosis and hypothermia and hormonal, immunological and cytokine production, alongside consumption and blood loss, and the dilutional effects of resuscitation may occur to varying extents depending on the type of tissue damaged, the type and extent of injury, predisposing to, or amplifying, activation of coagulation, platelets, fibrinolysis. These are discussed in detail within the article.

Topics: Acute Disease; Blood Coagulation Disorders; Humans; Resuscitation; Thrombelastography; Wounds and Injuries

PubMed: 25440402
DOI: 10.1111/anae.12914

Review

Authors: James Gauci, Lara Sammut, Martina Sciberras...

Crohn's disease (CD) is a lifelong, chronic inflammatory bowel disorder. The small bowel (SB) is involved to varying extents, and the clinical course may vary from an inflammatory type to a more complicated one with stricture, fistula, and abscess formation. Esophagogastroduodenoscopy and ileocolonoscopy with biopsies are the conventional endoscopic techniques that usually establish the diagnosis. On the other hand, CD may affect SB segments that cannot be reached through these procedures. Video capsule endoscopy and enteroscopy are additional endoscopic techniques that may allow further SB evaluation in such circumstances. Computed tomographic enterography, magnetic resonance enterography, and ultrasonography are radiologic techniques that serve as a crucial adjunct to endoscopic assessment. They enable the assessment of parts of the bowel that may be difficult to reach with conventional endoscopy; this allows for the detection of active inflammation, penetrating or stricturing disease, and the appreciation of extraintestinal complications. Both endoscopic and radiologic modalities play a role in establishing the diagnosis of CD, as well as determining the disease extent, activity and response to therapy. This review is intended to evaluate these modalities in terms of specificity, sensitivity, potential side-effects, and limiting factors. This should serve as a guide to the clinician for establishing the most appropriate and reliable test within a particular clinical context.

PubMed: 29991884
DOI: 10.20524/aog.2018.0268

Review

Authors: Joshua Ladau, Emiley A Eloe-Fadrosh

Microbial communities play a major role in disease, biogeochemical cycling, agriculture, and bioremediation. However, identifying the ecological processes that govern microbial community assembly and disentangling the relative impacts of those processes has proven challenging. Here, we propose that this discord is due to microbial systems being studied at different spatial, temporal, and phylogenetic scales. We argue that different processes dominate at different scales, and that through a more explicit consideration of spatial, temporal, and phylogenetic grains and extents (the two components of scale) a more accurate, clear, and useful understanding of microbial community assembly can be developed. We demonstrate the value of applying ecological concepts of scale to microbiology, specifically examining their application to nestedness, legacy effects, and taxa-area relationships of microbial systems. These proposed considerations of scale will help resolve long-standing debates in microbial ecology regarding the processes determining the assembly of microbial communities, and provide organizing principles around which hypotheses and theories can be developed.

Topics: Ecology; Microbiota; Phylogeny; Spatio-Temporal Analysis

PubMed: 31000488
DOI: 10.1016/j.tim.2019.03.003

Review

Authors: Sara Bettonte, Mattia Berton, Catia Marzolini...

Drug-drug interactions (DDIs) are one of the most frequent causes of adverse drug reactions or loss of treatment efficacy. The risk of DDIs increases with polypharmacy and is therefore of particular concern in individuals likely to present comorbidities (i.e., elderly or obese individuals). These special populations, and the population of pregnant women, are characterized by physiological changes that can impact drug pharmacokinetics and consequently the magnitude of DDIs. This review compiles existing DDI studies in elderly, obese, and pregnant populations that include a control group without the condition of interest. The impact of physiological changes on the magnitude of DDIs was then analyzed by comparing the exposure of a medication in presence and absence of an interacting drug for the special population relative to the control population. Aging does not alter the magnitude of DDIs as the related physiological changes impact the victim and perpetrator drugs to a similar extent, regardless of their elimination pathway. Conversely, the magnitude of DDIs can be changed in obese individuals or pregnant women, as these conditions impact drugs to different extents depending on their metabolic pathway.

PubMed: 35456623
DOI: 10.3390/pharmaceutics14040789

Review

Authors: Ming Li

Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and the atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole, and amisulpride, disrupt active maternal responses (e.g. pup retrieval, pup licking, and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. I argue that antipsychotic drugs at clinically relevant doses disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drug-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Among many potential receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs, with D2 receptors contributing more to typical antipsychotic-induced disruptions, whereas 5-HT2A/2C receptors contributing more to atypical drug-induced disruptions. The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior. This research not only helps understand the extent and mechanisms of impact of antipsychotic medications on human maternal care, but is also important for enhancing our understanding of the neurochemical basis of maternal behavior. It is also valuable for understanding the complete spectrum of therapeutic effects and side-effects of antipsychotic treatment. This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Female; Humans; Maternal Behavior; Rats; Social Behavior

PubMed: 26221833
DOI: 10.1097/FBP.0000000000000168

Authors: Siyuan Xu, Hui Huang, Huilei Dong...

BACKGROUND

Guidelines recommend total thyroidectomy (TT) to facilitate radioactive ablation and serological follow-up for intermediate- to high-risk papillary thyroid carcinoma (PTC). However, the association between surgical extent and tumor recurrence in these patients has not been well validated. We aimed to examine the association between the extent of surgery and recurrence in patients with completely resected unilateral intermediate- to high-risk PTC.

METHODS

Patients with completely resected unilateral PTC from 2000 to 2017 in a single institute were reviewed. Those who had extrathyroidal extension (ETE) or lymph node metastasis (LNM, cN1 or pN1 > 5 lymph nodes involved) were included for analysis. Cox proportional hazards models were applied to measure the association between surgical extent and recurrence-free survival (RFS) while adjusting for patient demographic, clinicopathological and treatment variables.

RESULTS

A total of 4550 patients (mean[SD] age, 43.0[11.7] years; 3379 women[74.3%]) were included. Of these patients, 2262(49.7%), 656(14.4%), 1032(22.7%), and 600 (13.2%) underwent lobectomy, TT, lobectomy + neck dissection (ND) and TT + ND, respectively. With a median follow-up period of 68 months, after multivariate adjustment, lobectomy was associated with a compromised RFS compared with other surgical extents (HR[95%CI], TT 0.537[0.333-0.866], P = 0.011, lobectomy + ND 0.531[0.392-0.720] P < 0.0001, TT + ND 0.446[0.286-0.697] P < 0.0001). RFS was similar between the two extents with ND (lobectomy + ND, HR [95%CI], 1.196 [0.759-1.885], P = 0.440).

CONCLUSION

Lobectomy alone is associated with an elevated recurrence risk in patients with unilateral intermediate- to high-risk PTC compared with larger surgical extents. However, lobectomy and ND may provide similar tumor control compared with the conventional approach of TT and ND.

Topics: Humans; Female; Adult; Thyroid Cancer, Papillary; Thyroidectomy; Lymph Nodes; Lymphatic Metastasis; Thyroid Neoplasms

PubMed: 37723469
DOI: 10.1186/s12885-023-11307-1

Authors: Changchang Ge, Yi Lu, Zhaofeng Shen...

BACKGROUND AND AIMS

Ulcerative colitis (UC) is a metabolism-related chronic intestinal inflammatory disease. Disease extent is a key parameter of UC. Using serum metabolic profiling to identify noninvasive biomarkers of disease extent may inform therapeutic decisions and risk stratification.

METHODS

The orthogonal partial least squares-discriminant analysis (OPLS-DA) was performed to identify the metabolites. Least absolute shrinkage and selection operator regression, random forest-recursive feature elimination, and support vector machine-recursive feature elimination algorithms were used to screen metabolites. Five machine learning algorithms (eXtreme Gradient Boosting, K-NearestNeighbor, Naive Bayes, random forest [RF], and SVM) were used to construct the prediction model.

RESULTS

A total of 220 differential metabolites between the patients with UC and healthy controls (HCs) were confirmed by the OPLS-DA model. Machine learning screened 8 essential metabolites for distinguishing patients with UC from HCs. A total of 23, 6, and 6 differential metabolites were obtained through machine learning between groups E1 and E2, E1 and E3, and E2 and E3. The RF model had a prediction accuracy of up to 100% in all 3 training sets. The serum levels of tridecanoic acid were significantly lower, and pelargonic acid was significantly higher in patients with extensive colitis than in the other groups. The serum level of asparaginyl valine in patients with rectal UC was significantly lower than that in the E2 and E3 groups.

CONCLUSIONS

Our findings revealed the metabolic landscape of UC and identified biomarkers for different disease extents, confirming the value of metabolites in predicting the occurrence and progression of UC.

Topics: Humans; Colitis, Ulcerative; Biomarkers; Machine Learning; Metabolomics; Male; Female; Adult; Middle Aged; Case-Control Studies; Severity of Illness Index; Discriminant Analysis

PubMed: 39903649
DOI: 10.1093/ecco-jcc/jjaf020

Authors: Xiang Zhao, Katja Boersma, Björn Gerdle...

OBJECTIVE

Psychological constructs related to the fear-avoidance model such as fear of movement, pain catastrophizing, and affective distress have been found to be inter-related among patients with chronic pain. However, relationships of these constructs have mostly been examined using regression-based analyses. This cross-sectional study employs a novel analytical approach, network analysis, to illustrate the complex interplays among these variables as well as pain intensity and pain interference.

METHODS

This study utilized the Swedish Quality Registry for Pain Rehabilitation, including data from 10,436 participants (76.0% women; M = 45.0 years). Networks were analyzed separately for patients with different pain extents (i.e., numbers of pain locations) as the interplays may differ qualitatively depending on pain extent.

RESULTS

We found that patients with a larger pain extent showed a worse clinical presentation (i.e., more depression and anxiety, increased fear of movement and pain interference), and their network differed from the patients with a smaller number of pain extent in terms of how strongly key variables were interconnected. In all network models, pain interference and catastrophizing showed consistently influential roles.

CONCLUSION

Our findings highlight the interactive nature of psychological aspects of pain and how interrelated associations differ depending on pain extent. Findings are discussed based on ideas on how both fear and pain become overgeneralized.

Topics: Humans; Female; Middle Aged; Male; Cross-Sectional Studies; Fear; Anxiety; Catastrophization; Chronic Pain; Surveys and Questionnaires

PubMed: 36773415
DOI: 10.1016/j.jpsychores.2023.111176