J. Pers. Med., Volume 11, Issue 10 (October 2021) – 106 articles

A family health history-based risk assessment is particularly valuable for guiding cancer screening and treatment strategies, yet an optimal implementation depends upon end-users’ values and needs. This is not only true prior to disease development, but also for those already affected. The aim of this study is to explore perceptions of the value of knowing one’s family health history (FHH)-based risk, experience using a patient-facing FHH tool and the potential of the tool for wider implementation. Twenty multi-ethnic Asian patients undergoing breast cancer treatment in Singapore completed an FHH-based risk assessment. Semi-structured one-on-one interviews were conducted and data were thematically analyzed. All participants were female and slightly more than half were Chinese. The acceptance and usage of an FHH risk assessment tool for cancers and its broader implementation was affected by a perceived importance of personal control over early detection, patient concerns of anxiety for themselves and their families due to risk results, concerns for genetic discrimination, adequacy of follow-up care plans and Asian cultural beliefs toward disease and dying. This study uniquely sheds light on the factors affecting Asian breast cancer patients’ perceptions about undergoing an FHH-based risk assessment, which should inform steps for a broader implementation in Asian healthcare systems. Full article

Background: Sarcopenia is a disease characterized by progressive reduction in muscle mass and strength or function. Although it is known that sarcopenia may be associated with environmental factors, studies suggest the identification of genes related to skeletal muscle maintenance that explain the susceptibility to the disease. Objective: To analyze the influence of NFkB1 gene polymorphism on susceptibility to sarcopenia in the elderly. Methods: This is a case-control study, which included 219 elderly people, 74 elderly people with sarcopenia, and 145 without sarcopenia. Samples were analyzed for NFkB1 gene polymorphism (rs28362491), genotyped in PCR, and followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 informative ancestral markers that were genotyped by multiplex PCR. We used logistic regression to identify differences in genotypic frequencies between elderly people with and without sarcopenia. Results: It was observed that the NFkB1 gene polymorphism presented frequencies of 24%, 50%, and 26% for the genotype DEL/DEL, DEL/INS, and INS/INS, respectively. Furthermore, elderly individuals with the INS/INS genotype had increased chances (p = 0.010; OR:2.943; 95%CI:1.301–6.654) for the development of sarcopenia. Conclusion: The INDEL polymorphism of the NFkB1 gene (rs28362491) may influence the susceptibility to sarcopenia in the elderly in elderly people in the Amazon. Full article

The liver is an irreplaceable organ in the human body, maintaining life activities and metabolism. Malignant tumors of the liver have a high mortality rate at present. Computer-aided segmentation of the liver and tumors has significant effects on clinical diagnosis and treatment. There are still many challenges in the segmentation of the liver and liver tumors simultaneously, such as, on the one hand, that convolutional kernels with fixed geometric structures do not match complex, irregularly shaped targets; on the other, pooling during convolution results in a loss of spatial contextual information of images. In this work, we designed a cascaded U-ADenseNet with coarse-to-fine processing for addressing the above issues of fully automatic segmentation. This work contributes multi-resolution input images and multi-layered channel attention combined with atrous spatial pyramid pooling densely connected in the fine segmentation. The proposed model was evaluated by a public dataset of the Liver Tumor Segmentation Challenge (LiTS). Our approach attained competitive liver and tumor segmentation scores that exceeded other methods across a wide range of metrics. Full article

The progressive loss of the regenerative potential of tissues is one of the most obvious consequences of aging, driven by altered intercellular communication, cell senescence and niche-specific stem cell exhaustion, among other drivers. Mesenchymal tissues, such as bone, cartilage and fat, which originate from mesenchymal stem cell (MSC) differentiation, are especially affected by aging. Senescent MSCs show limited proliferative capacity and impairment in key defining features: their multipotent differentiation and secretory abilities, leading to diminished function and deleterious consequences for tissue homeostasis. In the past few years, several interventions to improve human healthspan by counteracting the cellular and molecular consequences of aging have moved closer to the clinic. Taking into account the MSC exhaustion occurring in aging, advanced therapies based on the potential use of young allogeneic MSCs and derivatives, such as extracellular vesicles (EVs), are gaining attention. Based on encouraging pre-clinical and clinical data, this review assesses the strong potential of MSC-based (cell and cell-free) therapies to counteract age-related consequences in both physiological and premature aging scenarios. We also discuss the mechanisms of action of these therapies and the possibility of enhancing their clinical potential by exposing MSCs to niche-relevant signals. Full article

Although neuroendocrine tumours (NETs) are intensively studied, their diagnosis and consequently personalised therapy management is still puzzling due to their tumoral heterogeneity. In their theragnosis algorithm, receptor somatostatin scintigraphy takes the central place, the diagnosis receptor somatostatin analogue (RSA) choice depending on laboratory experience and accessibility. However, in all cases, the results depend decisively on correct radiotracer tumoral uptake quantification, where unfortunately there are still unrevealed clues and lack of standardization. We propose an improved method to quantify the biodistribution of gamma-emitting RSA, using tissular corrected uptake indices. We conducted a bi-centric retrospective study on 101 patients with different types of NETs. Three uptake indices obtained after applying new corrections to areas of interest drawn for the tumour and for three reference organs (liver, spleen and lung) were statistically analysed. For the corrected pathological uptake indices, the results showed a significant decrease in the error of estimating the occurrence of errors and an increase in the diagnostic predictive power for NETs, especially in the case of lung-referring corrected index. In conclusion, these results support the importance of corrected uptake indices use in the analysis of ^99mTcRSA biodistribution for a better personalised diagnostic accuracy of NETs patients. Full article

The aim of the present study was to correlate laboratory data and postprocedural parameters after conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) with the radiological response. The study consisted of a retrospective analysis of prospectively collected data from 70 consecutive patients who underwent cTACE. Laboratory parameters were assessed daily after cTACE and compared to pretreatment values. Post-treatment radiological response was assessed using mRECIST at one month from cTACE, and factors associated with treatment response (complete and objective response) were assessed by logistic regression analysis. The optimal cutoff points in predicting the complete response of target lesions were a 52% ALT and a 46% AST increase after cTACE compared to the pre-treatment values. Using multivariate analyses, >46% AST and >52% ALT increases with respect to the pre-treatment value were significantly correlated with the objective response (p = 0.03 and p = 0.04, respectively) and the complete response (p = 0.02 and p = 0.02, respectively). No patients experienced liver function deterioration after cTACE, and no specific treatment was required. This study showed that post-treatment transient transaminase elevation was predictive of objective response to superselective cTACE in clinical practice, representing a simple tool to guide treatment strategy of HCC patients in a tailored approach. Full article

Around 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and observational study including 416 patients who underwent BS was conducted (Clinical.Trials.gov- NCT02405949). 50 single nucleotide polymorphisms (SNPs) from 39 genes were examined. Receiver Operating Characteristic (ROC) curve analysis were used to calculate sensitivity and specificity. Satisfactory response to BS was defined as at nadir excess weight loss >50%. A good predictive model of response [area under ROC of 0.845 (95% CI 0.805–0.880), p < 0.001; sensitivity 90.1%, specificity 65.5%] was obtained by combining three clinical variables (age, type of surgery, presence diabetes) and nine SNPs located in ADIPOQ, MC4R, IL6, PPARG, INSIG2, CNR1, ELOVL6, PLIN1 and BDNF genes. This predictive model showed a significant higher area under ROC than the clinical score (p = 0.0186). The OBEGEN study shows the key role of combining clinical variables with genetic testing to increase the predictability of the weight loss response after BS. This finding will permit us to implement a personalized medicine which will be associated with a more cost-effective clinical practice. Full article

Peri-prosthetic joint infections (PJIs) dramatically affect human health, as they are associated with high morbidity and mortality rates. Two-stage revision arthroplasty is currently the gold standard treatment for PJI and consists of infected implant removal, an accurate debridement, and placement of antimicrobial impregnated poly-methyl-metha-acrylate (PMMA) spacer. The use of antibiotic-loaded PMMA (ALPMMA) spacers have showed a success rate that ranges from 85% to 100%. ALPMMA spacers, currently available on the market, demonstrate a series of disadvantages, closely linked to a low propensity to customize, seen as the ability to adapt to the patients’ anatomical characteristics, with consequential increase of surgical complexity, surgery duration, and post-operative complications. Conventionally, ALPMMA spacers are available only in three or four standard sizes, with the impossibility of guaranteeing the perfect matching of ALPMMA spacers with residual bone (no further bone loss) and gap filling. In this paper, a 3D model of an ALPMMA spacer is introduced to evaluate the cause- effect link between the geometric characteristics and the correlated clinical improvements. The result is a multivariable-oriented design able to effectively manage the size, alignment, stability, and the patients’ anatomical matching. The preliminary numerical results, obtained by using an “ad hoc” 3D virtual planning simulator, clearly point out that to restore the joint line, the mechanical and rotational alignment and the surgeon’s control on the thicknesses (distal and posterior thicknesses) of the ALPMMA spacer is mandatory. The numerical simulations campaign involved nineteen patients grouped in three different scenarios (Case N° 1, Case N° 2 and Case N° 3) whose 3D bone models were obtained through an appropriate data management strategy. Each scenario is characterized by a different incidence rate. In particular, the observed rates of occurrence are, respectively, equal to 17% (Case N° 1), 74% (Case N° 2), and 10% (Case N° 3). Full article

Iron deficiency anemia (IDA) accounts for most of the anemia in pregnancy, and iron is essential for neurodevelopment. Tics and Tourette’s syndrome (TS) are neurodevelopmental disorders that manifest in childhood. A few studies reported an inconclusive association between iron deficiency and tics in children. No study has investigated the relationship between prenatal maternal anemia and tics in children. We aimed to assess the relationship between prenatal anemia exposure and the incidence of tics or TS in offspring. We linked the Taiwan National Health Insurance Research Database to the Maternal and Child Health Database for the analysis and identified 153,854 children with prenatal anemia exposure and 2,014,619 children without prenatal anemia exposure from 2004 to 2016 and followed them through 2017. Cox regression models were applied to compare the risk of tics or TS between the exposed and nonexposed groups. Among the exposed group, 37,832 were exposed at ≤12 weeks of gestational age (GA) and 116,022 at >12 weeks of GA. We observed an increased risk of tics and TS in those exposed at ≤12 weeks compared with the nonexposed group (adjusted hazard ratio (aHR) = 1.23, 95% confidence interval (CI): 1.12–1.34). The result remained consistent after adjusting for birth year, sex, birth order, maternal age, low-income levels, gestational age, birth weight, and alcohol use and smoking during pregnancy (aHR = 1.16, CI: 1.04–1.28). Fetuses exposed to maternal anemia at ≤12 weeks of GA are at high risk of tics or TS. However, this effect was attenuated to insignificance in the sibling comparison. Our study highlights the importance of detection of anemia during pregnancy and proper timing of iron supplementation. Full article

Olfactory and gustatory dysfunctions are important initial symptoms of coronavirus disease 2019 (COVID-19). However, the treatment modality for these conditions has yet to be clearly established. Therefore, most physicians have been administering empirical treatments for COVID-19-associated olfactory dysfunction, including topical or systemic steroid supplementation and olfactory training. In this literature review, we summarize the clinical course and effects of various treatments currently being conducted in patients with COVID-19-associated olfactory and gustatory dysfunctions. Full article

Low-grade gliomas (LGGs) are brain tumors characterized by their slow growth and infiltrative nature. Treatment options for these tumors are surgery, radiation therapy and chemotherapy. The optimal use of radiation therapy and chemotherapy is still under study. In this paper, we construct a mathematical model of LGG response to combinations of chemotherapy, specifically to the alkylating agent temozolomide and radiation therapy. Patient-specific parameters were obtained from longitudinal imaging data of the response of real LGG patients. Computer simulations showed that concurrent cycles of radiation therapy and temozolomide could provide the best therapeutic efficacy in-silico for the patients included in the study. The patient cohort was extended computationally to a set of 3000 virtual patients. This virtual cohort was subject to an in-silico trial in which matching the doses of radiotherapy to those of temozolomide in the first five days of each cycle improved overall survival over concomitant radio-chemotherapy according to RTOG 0424. Thus, the proposed treatment schedule could be investigated in a clinical setting to improve combination treatments in LGGs with substantial survival benefits. Full article

Hearing impairment is a frequent human sensory impairment. It was estimated that over 50% of those aged >75 years experience hearing impairment in the United States. Several hearing impairment–related factors are detectable through screening; thus, further deterioration can be avoided. Early identification of hearing impairment is the key to effective management. However, hearing screening resources are scarce or inaccessible, underlining the importance of developing user-friendly mobile health care systems for universal hearing screening. Mobile health (mHealth) applications (apps) act as platforms for personalized hearing screening to evaluate an individual’s risk of developing hearing impairment. We aimed to evaluate and compare the accuracy of smartphone-based air conduction and bone conduction audiometry self-tests with that of standard air conduction and bone conduction pure-tone audiometry tests. Moreover, we evaluated the use of smartphone-based air conduction and bone conduction audiometry self-tests in conductive hearing loss diagnosis. We recruited 103 patients (206 ears) from an otology clinic. All patients were aged ≥20 years. Patients who were diagnosed with active otorrhea was excluded. Moderate hearing impairment was defined as hearing loss with mean hearing thresholds >40 dB. All patients underwent four hearing tests performed by a board-certified audiologist: a smartphone-based air conduction audiometry self-test, smartphone-based bone conduction audiometry self-test, standard air-conduction pure-tone audiometry, and standard bone conduction pure-tone audiometry. We compared and analyzed the results of the smartphone-based air conduction and bone conduction audiometry self-tests with those of the standard air conduction and bone conduction pure-tone audiometry tests. The sensitivity of the smartphone-based air conduction audiometry self-test was 0.80 (95% confidence interval CI = 0.71–0.88) and its specificity was 0.84 (95% CI = 0.76–0.90), respectively. The sensitivity of the smartphone-based bone conduction audiometry self-test was 0.64 (95% CI = 0.53–0.75) and its specificity was 0.71 (95% CI = 0.62–0.78). Among all the ears, 24 were diagnosed with conductive hearing loss. The smartphone-based audiometry self-tests correctly diagnosed conductive hearing loss in 17 of those ears. The personalized smartphone-based audiometry self-tests correctly diagnosed hearing loss with high sensitivity and high specificity, and they can be a reliable screening test to rule out moderate hearing impairment among the population. It provided patients with moderate hearing impairment with personalized strategies for symptomatic control and facilitated individual case management for medical practitioners. Full article

To compare and contrast the accuracy of piezoelectric ultrasonic insert (PUI) and trephine bur (TB) osteotomy site preparation techniques for apical location. (1) Material and methods: A total of 138 osteotomy site preparations were randomly distributed into one of two study groups. Group A: TB technique (n = 69) and B: PUI technique (n = 69). A preoperative cone-beam computed tomography scan and an intraoral scan were performed and uploaded to implant-planning software to plan the virtual osteotomy site preparations for apical location. Subsequently, the osteotomy site preparations were performed in the experimental models with both osteotomy site preparation techniques and a postoperative CBCT scan was performed and uploaded into the implant-planning software and matched with the virtually planned osteotomy site preparations to measure the deviation angle and horizontal deviation as captured at the coronal entry point and apical end-point between osteotomy site preparations using Student’s t-test statistical analysis. (2) Results: The paired t-test found statistically significant differences at the coronal entry-point deviations (p = 0.0104) and apical end-point deviations (p = 0.0104) between the TB and PUI study groups; however, no statistically significant differences were found in the angular deviations (p = 0.309) between the trephine bur and piezoelectric ultrasonic insert study groups. (3) Conclusions: The results showed that the TB is more accurate than the PUI for apical location. Full article

Chronic lung disease is associated with tremendous social and economic burden worldwide. The aim of this study was to investigate the sex-specific risk factors for changes in lung function in a large longitudinal study. We included 9059 participants from the Taiwan Biobank. None of the participants had a history of smoking, asthma, emphysema or bronchitis. Lung function was assessed using spirometry measurements of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Change in the FEV1/FVC (ΔFEV1/FVC) was calculated as a follow-up FEV1/FVC minus baseline FEV1/FVC. Linear regression analysis was used to identify associations between variables and ΔFEV1/FVC in the male and female participants. After multivariable adjustments, the male participants (vs. females; p = 0.021) were significantly associated with a low ΔFEV1/FVC. In addition, the male participants with low aspartate aminotransferase (AST) (p = 0.003), high alanine aminotransferase (ALT) (p = 0.006) and a low estimated glomerular filtration rate (eGFR) (p = 0.003) were significantly associated with a low ΔFEV1/FVC. For the female participants, low systolic blood pressure (p = 0.005), low diastolic blood pressure (p = 0.031), low AST (p < 0.001), high ALT (p < 0.001) and a low eGFR (p = 0.001) were significantly associated with a low ΔFEV1/FVC. In this large follow-up study, we found that the male participants had a faster decrease in the FEV1/FVC than the female participants. In addition, liver and renal functions were correlated with changes in lung function in both the male and female participants. Our findings provide useful information on sex-specific changes in lung function. Full article

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. Treatment is aimed at slowing down the course of the disease and mitigating its symptoms. One of the first-line treatments used in patients with MS is glatiramer acetate (GA). However, in clinical practice, a response rate of between 30% and 55% is observed. This variability in the effectiveness of the medication may be influenced by genetic factors such as polymorphisms in the genes involved in the pathogenesis of MS. Therefore, this review assesses the impact of genetic variants on the response to GA therapy in patients diagnosed with MS. The results suggest that a relationship exists between the effectiveness of the treatment with GA and the presence of polymorphisms in the following genes: CD86, CLEC16A, CTSS, EOMES, MBP, FAS, TRBC1, IL1R1, IL12RB2, IL22RA2, PTPRT, PVT1, ALOX5AP, MAGI2, ZAK, RFPL3, UVRAG, SLC1A4, and HLA-DRB1*1501. Consequently, the identification of polymorphisms in these genes can be used in the future as a predictive marker of the response to GA treatment in patients diagnosed with MS. Nevertheless, there is a lack of evidence for this and more validation studies need to be conducted to apply this information to clinical practice. Full article

Breast cancer is the most prominent type of cancer among women. Understanding the microenvironment of breast cancer and the interactions between cells and cytokines will lead to better treatment approaches for patients. In this study, we developed a data-driven mathematical model to investigate the dynamics of key cells and cytokines involved in breast cancer development. We used gene expression profiles of tumors to estimate the relative abundance of each immune cell and group patients based on their immune patterns. Dynamical results show the complex interplay between cells and molecules, and sensitivity analysis emphasizes the direct effects of macrophages and adipocytes on cancer cell growth. In addition, we observed the dual effect of IFN-$\gamma$ on cancer proliferation, either through direct inhibition of cancer cells or by increasing the cytotoxicity of CD8+ T-cells. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the loss of dopaminergic neurons. The vast majority of PD patients develop the disease sporadically and it is assumed that the cause lies in polygenic and environmental components. The overall polygenic risk is the result of a large number of common low-risk variants discovered by large genome-wide association studies (GWAS). Polygenic risk scores (PRS), generated by compiling genome-wide significant variants, are a useful prognostic tool that quantifies the cumulative effect of genetic risk in a patient and in this way helps to identify high-risk patients. Although there are limitations to the construction and application of PRS, such as considerations of limited genetic underpinning of diseases explained by SNPs and generalizability of PRS to other populations, this personalized risk prediction could make a promising contribution to stratified medicine and tailored therapeutic interventions in the future. Full article

We investigated whether textural parameters of peritumoral breast adipose tissue (AT) based on F-18 fluorodeoxyglucose (FDG) PET/CT could predict axillary lymph node metastasis in patients with breast cancer. A total of 326 breast cancer patients with preoperative FDG PET/CT were retrospectively enrolled. PET/CT images were visually assessed and the maximum FDG uptake of axillary lymph nodes (LN SUVmax) was measured. From peritumoral breast AT, 38 textural features of PET imaging were extracted. The diagnostic ability of PET based on visual analysis, LN SUVmax, and textural features of peritumoral breast AT for predicting axillary lymph node metastasis were assessed using the area under the receiver operating characteristic curve (AUC) values. Among the 38 peritumoral breast AT textural features, grey-level co-occurrence matrix (GLCM) entropy showed the highest AUC value (0.830) for predicting axillary lymph node metastasis. The value of GLCM entropy was higher than that of visual analysis (0.739; p < 0.05) and the AUC value was comparable to that of LN SUVmax (0.793; p > 0.05). In the subgroup analysis of patients with negative findings on visual analysis, GLCM entropy still showed a high diagnostic ability (AUC: 0.759) in predicting lymph node metastasis. The findings suggest a potential diagnostic role of PET/CT imaging features of peritumoral breast AT in predicting axillary lymph node metastasis in patients with breast cancer. Full article

Epilepsy is a neurological disorder of the brain that causes frequent occurrence of seizures. Electroencephalography (EEG) is a tool that assists neurologists in detecting epileptic seizures caused by an unexpected flow of electrical activities in the brain. Automated detection of an epileptic seizure is a crucial task in diagnosing epilepsy which overcomes the drawback of a visual diagnosis. The dataset analyzed in this article, collected from Children’s Hospital Boston (CHB) and the Massachusetts Institute of Technology (MIT), contains long-term EEG records from 24 pediatric patients. This review paper focuses on various patient-dependent and patient-independent personalized medicine approaches involved in the computer-aided diagnosis of epileptic seizures in pediatric subjects by analyzing EEG signals, thus summarizing the existing body of knowledge and opening up an enormous research area for biomedical engineers. This review paper focuses on the features of four domains, such as time, frequency, time-frequency, and nonlinear features, extracted from the EEG records, which were fed into several classifiers to classify between seizure and non-seizure EEG signals. Performance metrics such as classification accuracy, sensitivity, and specificity were examined, and challenges in automatic seizure detection using the CHB-MIT database were addressed. Full article

Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of the cutaneous epithelium, is the second most common skin cancer after basal cell carcinoma (BCC). Unlike BCC, cSCC exhibits a greater aggressiveness and the ability to metastasize to any organ in the body. Chronic inflammation and immunosuppression are important processes linked to the development of cSCC. The tumor can occur de novo or from the histological transformation of preexisting actinic keratoses (AK). Malignant cells exhibit a higher amount of sialic acid in their membranes than normal cells, and changes in the amount, type, or linkage of sialic acid in malignant cell glycoconjugates are related to tumor progression and metastasis. The aim of our study was to investigate the sialyation in patients with cSCC and patients with AK. We have determined the serum levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), beta-galactoside 2,6-sialyltransferase I (ST6GalI), and neuraminidase 3 (NEU3) in 40 patients with cSCC, 28 patients with AK, and 40 healthy subjects. Data analysis indicated a significant increase in serum levels of TSA (p < 0.001), LSA (p < 0.001), ST6GalI (p < 0.001), and NEU3 (p < 0.001) in the cSCC group compared to the control group, whereas in patients with AK only the serum level of TSA was significantly higher compared to the control group (p < 0.001). When the cSCC and AK groups were compared, significant differences between the serum levels of TSA (p < 0.001), LSA (p < 0.001), ST6GalI (p < 0.001) and NEU3 (p < 0.001) were found. The rate of synthesis of sialoglycoconjugates and their rate of enzymatic degradation, expressed by the ST6GalI/NEU3 ratio, is 1.64 times lower in the cSCC group compared to the control group (p < 0.01) and 1.53 times lower compared to the AK group (p < 0.01). The tumor diameter, depth of invasion, and Ki67 were associated with higher levels of TSA and LSA. These results indicate an aberrant sialylation in cSCC that correlates with tumor aggressiveness. Full article

Hypophysitis is a rare and potentially life-threatening disease, characterized by an elevated risk of complications, such as the occurrence of acute central hypoadrenalism, persistent hypopituitarism, or the extension of the inflammatory process to the neighboring neurological structures. In recent years, a large number of cases has been described. The diagnosis of hypophysitis is complex because it is based on clinical and radiological criteria. Due to this, the integration of molecular and genetic biomarkers can help physicians in the diagnosis of hypophysitis and play a role in predicting disease outcome. In this paper, we review current knowledge about molecular and genetic biomarkers of hypophysitis with the aim of suggesting a possible integration of these biomarkers in clinical practice. Full article

Breast cancer is the most common female cancer worldwide, and breast cancer accounts for 30% of female cancers. Of all the treatment modalities, breast cancer survivors who have undergone chemotherapy might complain about cognitive impairment during and after cancer treatment. This phenomenon, chemo-brain, is used to describe the alterations in cognitive functions after receiving systemic chemotherapy. Few reports detect the chemotherapy-induced cognitive impairment (CICI) by performing functional MRI (fMRI) and a deep learning analysis. In this study, we recruited 55 postchemotherapy breast cancer survivors (C+ group) and 65 healthy controls (HC group) and extracted mean fractional amplitudes of low-frequency fluctuations (mfALFF) from resting-state fMRI as our input feature. Two state-of-the-art deep learning architectures, ResNet-50 and DenseNet-121, were transformed to 3D, embedded with squeeze and excitation (SE) blocks and then trained to differentiate cerebral alterations based on the effect of chemotherapy. An integrated gradient was applied to visualize the pattern that was recognized by our model. The average performance of SE-ResNet-50 models was an accuracy of 80%, precision of 78% and recall of 70%; on the other hand, the SE-DenseNet-121 model reached identical results with an average of 80% accuracy, 86% precision and 80% recall. The regions with the greatest contributions highlighted by the integrated gradients algorithm for differentiating chemo-brain were the frontal, temporal, parietal and occipital lobe. These regions were consistent with other studies and strongly associated with the default mode and dorsal attention networks. We constructed two volumetric state-of-the-art models and visualized the patterns that are critical for identifying chemo-brains from normal brains. We hope that these results will be helpful in clinically tracking chemo-brain in the future. Full article

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD. Full article

Background: To date, in personalized medicine approaches, single-cell analyses such as circulating tumour cells (CTC) are able to reveal small structural cell modifications, and therefore can retrieve several biophysical cell properties, such as the cell dimension, the dimensional relationship between the nucleus and the cytoplasm and the optical density of cellular sub-compartments. On this basis, we present in this study a new morphological measurement approach for the detection of vital CTC from pleural washing in individual non-small cell lung cancer (NSCLC) patients. Materials and methods: After a diagnosis of pulmonary malignancy, pleural washing was collected from nine NSCLC patients. The collected samples were processed with a density gradient separation process. Light scattering analysis was performed on a single cell. The results of this analysis were used to obtain the cell’s biophysical pattern and, later on, as basis for Machine Learning (ML) on unknown samples. Results: Morphological single-cell analysis followed by ML show a predictive picture for an NSCLC patient, screening that it is possible to distinguish CTC from other cells. Moreover, we find that the proposed measurement approach was fast, reliable, label-free, identifying and count CTC in a biological fluid. Conclusions: Our findings demonstrate that CTC Biophysical Profile by Pure Light Scattering in NSCLC could be used as a promising diagnostic candidate in NSCLC patients. Full article

Electroretinography (ERG) is an important and well-established examination for retinal and visual pathway diseases. This study reviewed the medical records of patients who received full-field ERG (ffERG) at a single medical center between 2012 and 2019, which was an 8-year experience in the clinical contribution of ERG. Based on the indication for scheduling ffERG and the final diagnosis, patients could be classified into six groups: ‘retinal dystrophies’, ‘other retinal or macular diseases’, ‘optic neuropathies’, ‘visual complaints’, ‘systemic diseases’, and ‘others’. A total of 1921 full-field electroretinograms (ffERGs) (1655 patients) were included. The average number of ffERGs performed per year was 262 and the number of annual ffERGs was constant. The ‘retinal dystrophies’ group accounted for 36.5% of the studied population, followed by the ‘other retinal or macular diseases’ group (20.2%). The most common systemic disease was central nervous system disease. The rates of abnormal ffERGs in the ‘systemic diseases’, ‘optic neuropathies’, and ‘visual complaints’ groups were 27.3%, 22.6%, and 10.1%, respectively (p < 0.001). Higher rates were found in patients <20 years old in the ‘systemic diseases’ and ‘optic neuropathies’ groups; epilepsy and optic nerve atrophy were the most common diagnoses, respectively. In brief, by quantifying the functional response in the retina, ffERG is indispensable for diagnosis and prognosis in ophthalmologic and multidisciplinary practice. Full article

Disorders of gut–brain interactions (DGBIs) are heterogeneous in nature and intertwine with diverse pathophysiological mechanisms. Regular functioning of the gut requires complex coordinated interplay between a variety of gastrointestinal (GI) cell types and their functions are regulated by multiple mechanisms at the transcriptional, post-transcriptional, translational, and post-translational levels. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression by binding to specific mRNA targets to repress their translation and/or promote the target mRNA degradation. Dysregulation of miRNAs might impair gut physiological functions leading to DGBIs and gut motility disorders. Studies have shown miRNAs regulate gut functions such as visceral sensation, gut immune response, GI barrier function, enteric neuronal development, and GI motility. These biological processes are highly relevant to the gut where neuroimmune interactions are key contributors in controlling gut homeostasis and functional defects lead to DGBIs. Although extensive research has explored the pathophysiology of DGBIs, further research is warranted to bolster the molecular mechanisms behind these disorders. The therapeutic targeting of miRNAs represents an attractive approach for the treatment of DGBIs because they offer new insights into disease mechanisms and have great potential to be used in the clinic as diagnostic markers and therapeutic targets. Here, we review recent advances regarding the regulation of miRNAs in GI pacemaking cells, immune cells, and enteric neurons modulating pathophysiological mechanisms of DGBIs. This review aims to assess the impacts of miRNAs on the pathophysiological mechanisms of DGBIs, including GI dysmotility, impaired intestinal barrier function, gut immune dysfunction, and visceral hypersensitivity. We also summarize the therapeutic alternatives for gut microbial dysbiosis in DGBIs, highlighting the clinical insights and areas for further exploration. We further discuss the challenges in miRNA therapeutics and promising emerging approaches. Full article

Binge eating is a transdiagnostic eating disorder symptom that can occur in patients with anorexia nervosa (AN), persisting after weight restoration, and impeding their recovery. However, little is known about the biological predictors of binge eating after AN weight restoration. The goals of this exploratory study of 73 females with AN were: (1) to examine changes in cortisol, the adrenocorticotropic hormone, norepinephrine, ghrelin (total and active), and leptin levels across the admission, discharge, and 3 months post-discharge from the inpatient AN weight restoration; and (2) to determine whether the target hormones were associated with objective or subjective binge eating (OBE or SBE). The participants completed the self-reported Eating Disorder Examination Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory-II, and provided fasting whole blood samples for hormone assays. The results showed significant changes in body mass index (BMI), cortisol, total ghrelin, and leptin levels over the three time points. The cortisol levels at admission and discharge were significantly associated with the number of SBE episodes at 3 months post-discharge. Findings suggest the need to replicate and confirm the role of cortisol in predicting the emergence of SBE and uncover the mechanisms underlying SBE and cortisol to prevent SBE and its negative consequences. Full article

Since the inception of their profession, neurosurgeons have defined themselves as physicians with a surgical practice. Throughout time, neurosurgery has always taken advantage of technological advances to provide better and safer care for patients. In the ongoing precision medicine surge that drives patient-centric healthcare, neurosurgery strives to effectively embrace the era of data-driven medicine. Neuro-oncology best illustrates this convergence between surgery and precision medicine with the advent of molecular profiling, imaging and data analytics. This convenient convergence paves the way for new preventive, diagnostic, prognostic and targeted therapeutic perspectives. The prominent advances in healthcare and big data forcefully challenge the medical community to deeply rethink current and future medical practice. This work provides a historical perspective on neurosurgery. It also discusses the impact of the conceptual shift of precision medicine on neurosurgery through the lens of neuro-oncology. Full article

The study of postoperative nausea and vomiting (PONV) has been ongoing since the early days of general anesthesia. The search for risk factors of PONV and the development of new agents to treat PONV are the two main strategies to combat the adverse side effects of general anesthesia. Female sex, non-smoking status, a history of PONV/motion sickness, and postoperative opioid use are the four independent risk factors for PONV derived after a series of prospective studies, evidence-based systematic reviews, and meta-analyses. The two frequently asked questions that arise ask whether risk factors apply to different clinical settings and whether prevention measures of PONV can be surgery dependent. We conducted a comprehensive review of 665 patients who underwent primary total knee arthroplasty (TKA) between January and December 2019. As nausea is subjective and its measurement is not standardized, postoperative vomiting (POV) was used as a study endpoint. The exclusion criteria were desflurane anesthesia, spinal anesthesia, anesthesia without bispectral index monitoring, and day surgery. Three well-recognized risk factors, consisting of body weight, sevoflurane consumption, and postoperative opioid consumption, were not considered as independent risk factors of POV, while female sex, preoperative adductor canal block (ACB), and dexamethasone were identified as being so in this study. The risk of POV in the female sex was 2.49 times that in the male sex; however, when dexamethasone was used, this risk was reduced by >40% compared with no antiemetic use, and by >50% when patients received preoperative ACB compared with those without the block. The clinical characteristics of our TKA patients—female dominance, old age, and their fairly constant body weights that were distinct from those of other surgical patients—suggested that age may play a crucial role in determining the relative contributions of the different risk factors of POV. We concluded that risk factors of POV are dependent on clinical settings. Based on these results, it is reasonable to speculate that a surgery-dependent plan for the prevention of POV is feasible for patients in similar clinical settings. Full article

Vertically oriented femoral neck fractures (FNFs) are known to be especially unstable FNFs, and they have a higher associated risk of failure. The dynamic hip screw (DHS) technique and the cannulated cancellous screw (CCS) technique are the two main fixation techniques used in the treatment of FNFs. However, no large clinical study has compared the DHS and CCS techniques in patients with high-shear-angle FNFs. MEDLINE, Embase, Cochrane Library, and Web of Science were systematically searched for studies that compared the DHS and CCS techniques for the treatment of Pauwels type II or type III FNF. Pooled analysis was performed to identify differences between the DHS and CCS techniques in Pauwels type II or type III FNF, with a focus on postoperative complications such as fracture nonunion and osteonecrosis of the femoral head (ONFH). We included five studies with a total of 252 patients. The DHS technique was used in 96 patients (DHS group), and the CCS technique was used in 156 patients (CCS group). The pooled analysis revealed that the nonunion rate in the CCS group was significantly higher than that in the DHS group (OR = 0.32; 95% CI, 0.11–0.96; p = 0.04, I² = 0%), but there was no difference in the incidence of ONFH between the groups (OR = 0.98; 95% CI, 0.20–4.73; p = 0.98, I² = 53%). For vertically oriented FNFs, the DHS technique is more favorable and has a lower risk of fracture nonunion than the CCS technique. Full article