J. Pers. Med., Volume 11, Issue 7 (July 2021) – 94 articles

Background: The purpose of this study was to identify the needs, preferences, and values of patients with differentiated thyroid cancer (DTC) and the physicians treating patients with DTC regarding two different treatment decisions, namely: the extent of primary surgery (low-risk patients) and the tyrosine kinase inhibitor (TKI) treatment (high-risk patients). Methods: A qualitative study was conducted. There were two physician focus groups discussing the extent of primary surgery. One included endocrinologists (n = 4) and surgeons (n = 5), and the other included nuclear medicine physicians (n = 3) treating patients with low-risk DTC. The physicians focus group discussing waiting or starting TKIs included endocrinologists (n = 2) and oncologists (n = 5) treating patients with advanced radioactive iodide (RAI) refractory DTC. Moreover, one patient focus group per treatment decision took place. In total 13 patients and 19 physicians participated. Interviews were audio-taped, fully transcribed verbatim, and analyzed. Results: Several themes were identified. Patients, but not physicians, mentioned the importance of a strong doctor–patient relationship. Patients in both treatment decision groups wanted to receive more detailed information, whereas physicians preferred providing more general information. Patients in the TKI decision group focused on palliative care, whereas physicians focused more on the effect and benefit of TKIs. Conclusions: Considering the identified themes in DTC, based on the patients’ needs, preferences, and values, enables us to improve doctor–patient communication and to develop decision support tools. Full article

Antigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery–validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines’ quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933–0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127–80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846–0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover–validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments. Full article

Parkinson’s disease (PD) is a chronic, progressive neurological disorder and the second most common neurodegenerative condition. Advanced PD is complicated by erratic gastric absorption, delayed gastric emptying in turn causing medication overload, and hence the emergence of motor and non-motor fluctuations and dyskinesia, which is initially predictable and then becomes unpredictable. As the patient progresses to the advanced stage, advanced Parkinson’s disease (APD) is characterized by refractory motor and non motor fluctuations, unpredictable OFF periods, and troublesome dyskinesias. The management of APD is a complex affair. There is growing recognition that GI dysfunction is common in PD, with virtually the entire GI system (the upper and lower GI tracts) causing problems from dribbling to defecation. The management of PD should focus on personalized care addressing both motor and non-motor symptoms, ideally including not only dopamine replacement but also associated non-dopaminergic circuits, particularly focusing on noradrenergic, serotonergic, and cholinergic therapies bypassing the gastrointestinal tract (GIT) by infusion or device-aided therapies (DAT), including levodopa–carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, which are available in many countries for the management of the advanced stage of Parkinson’s disease (APD). The PKG (KinetiGrap) can be used as a continuous objective monitoring (COM) aid, as a screening tool to help to identify advanced PD (APD) patients suitable for DAT, and can thus improve clinical outcomes. Full article

Apathy is a neuropsychiatric condition characterized by reduced motivation, initiative, and interest in daily life activities, and it is commonly reported in several neurodegenerative disorders. The study aims to investigate large-scale brain networks involved in apathy syndrome in patients with frontotemporal dementia (FTD) and Parkinson’s disease (PD) compared to a group of healthy controls (HC). The study sample includes a total of 60 subjects: 20 apathetic FTD and PD patients, 20 non apathetic FTD and PD patients, and 20 HC matched for age. Two disease-specific apathy-evaluation scales were used to measure the presence of apathy in FTD and PD patients; in the same day, a 3T brain magnetic resonance imaging (MRI) with structural and resting-state functional (fMRI) sequences was acquired. Differences in functional connectivity (FC) were assessed between apathetic and non-apathetic patients with and without primary clinical diagnosis revealed, using a whole-brain, seed-to-seed approach. A significant hypoconnectivity between apathetic patients (both FTD and PD) and HC was detected between left planum polare and both right pre- or post-central gyrus. Finally, to investigate whether such neural alterations were due to the underlying neurodegenerative pathology, we replicated the analysis by considering two independent patients’ samples (i.e., non-apathetic PD and FTD). In these groups, functional differences were no longer detected. These alterations may subtend the involvement of neural pathways implicated in a specific reduction of information/elaboration processing and motor outcome in apathetic patients. Full article

Tuberculosis (TB) survivors experience post-TB lung damage and ventilatory function disorders. However, the proportions of obstructive and restrictive ventilatory disorders as well as normal ventilation among subjects with prior TB are unknown. In addition, the impacts of ventilatory disorder and its severity on respiratory symptoms, physical activity limitations, and the quality of life in subjects with prior TB remain unclear. Subjects who participated in the Korean National Health and Nutritional Examination Survey 2007–2016 were enrolled in this study. We evaluated the impact of each ventilatory disorder and its severity on respiratory symptoms, physical activity limitations, and quality of life (measured by the EuroQoL five dimensions questionnaire [EQ-5D] index values) in subjects with prior TB. Among 1466 subjects with prior TB, 29% and 16% had obstructive ventilatory disorders and restrictive ventilatory disorders, respectively. Mild and moderate obstructive ventilatory disorders were not associated with respiratory symptoms, physical activity limitations, or EQ-5D index value compared with normal ventilation; however, severe obstructive ventilatory disorders were associated with more respiratory symptoms (adjusted odds ratio [aOR] = 13.62, 95% confidence interval [CI] = 4.64–39.99), more physical activity limitation (aOR = 218.58, 95% CI = 26.82–1781.12), and decreased EQ-5D index (adjusted coefficient = −0.06, 95% CI = (−0.12–−0.10) compared with normal ventilation. Mild restrictive ventilatory disorders were associated with more respiratory symptoms (aOR = 2.10, 95% CI = 1.07–4.14) compared with normal ventilation, while moderate (aOR = 5.71, 95% CI = 1.14–28.62) and severe restrictive ventilatory disorders (aOR = 9.17, 95% CI = 1.02–82.22) were associated with physical activity limitation compared with normal ventilation. In conclusion, among subjects with prior TB, 29% and 16% developed obstructive and restrictive ventilatory disorders, respectively. Severe obstructive ventilatory disorder was associated with more respiratory symptoms, more physical activity limitation, and poorer quality of life, while severe restrictive ventilatory disorder was associated with more physical activity limitations. Full article

Purpose: Cytochrome P450 (CYP) is involved in the metabolism of statins; CYP3A5 is the main enzyme responsible for lipophilic statin metabolism. However, the evidence of the association between CYP3A5*3 polymorphism and the risk of statin-induced adverse events remains unclear. Therefore, this study aimed to perform a systematic review and meta-analysis to investigate the relationship between the CYP3A5*3 polymorphism and the risk of statin-induced adverse events. Methods: The PubMed, Web of Science, and EMBASE databases were searched for qualified studies published until August 2020. Observational studies that included the association between statin-induced adverse events and the CYP3A5*3 polymorphism were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated to assess the strength of the relationship. The Mantel–Haenszel method was used to provide the pooled ORs. Heterogeneity was estimated with I² statistics and publication bias was determined by Begg’s and Egger’s test of the funnel plot. Data analysis was performed using Review Manager (version 5.4) and R Studio (version 3.6). Results: In total, data from 8 studies involving 1614 patients were included in this meta-analysis. The CYP3A5*3 polymorphism was found to be associated with the risk of statin-induced adverse events (*3/*3 vs. *1/*1 + *1/*3: OR = 1.40, 95% CI = 1.08–1.82). For myopathy, the pooled OR was 1.30 (95% CI: 0.96–1.75). The subgroup analysis of statin-induced myopathy revealed a trend, which did not achieve statistical significance. Conclusions: This meta-analysis demonstrated that the CYP3A5*3 polymorphism affected statin-induced adverse event risk. Therefore, CYP3A5 genotyping may be useful to predict statin toxicity. Full article

In pediatric acquired brain injury, heterogeneity of functional response to specific rehabilitation treatments is a key confound to medical decisions and outcome prediction. We aimed to identify patient subgroups sharing comparable trajectories, and to implement a method for the early prediction of the long-term recovery course from clinical condition at first discharge. 600 consecutive patients with acquired brain injury (7.4 years ± 5.2; 367 males; median GCS = 6) entered a standardized rehabilitation program. Functional Independent Measure scores were measured yearly, until year 7. We classified the functional trajectories in clusters, through a latent class model. We performed single-subject prediction of trajectory membership in cases unseen during model fitting. Four trajectory types were identified (post.prob. > 0.95): high-start fast (N = 92), low-start fast (N = 168), slow (N = 130) and non-responders (N = 210). Fast responders were older (chigh = 1.8; clow = 1.1) than non-responders and suffered shorter coma (chigh = −14.7; clow = −4.3). High-start fast-responders had shorter length of stay (c = −1.6), and slow responders had lower incidence of epilepsy (c = −1.4), than non-responders (p < 0.001). Single-subject trajectory could be predicted with high accuracy at first discharge (accuracy = 0.80). In conclusion, we stratified patients based on the evolution of their response to a specific treatment program. Data at first discharge predicted the response over 7 years. This method enables early detection of the slow responders, who show poor post-acute functional gains, but achieve recovery comparable to fast responders by year 7. Further external validation in other rehabilitation programs is warranted. Full article

Sorafenib and lenvatinib are the only multikinase inhibitors (MKIs) approved for the treatment of radioactive iodine refractory differentiated thyroid cancer (RR-DTC). Although they have been demonstrated to improve progression free survival and overall response rate, the risk of toxicities is very high, worsening patients’ quality of life. Therefore, predicting MKI treatment outcomes in the setting of RR-DTC is very challenging for optimizing patients’ management. The current review provides an overview of the predictive factors for the response and survival of sorafenib and lenvatinib in RR-DTC. In this setting, a systemic therapy should be considered after conducting a multidisciplinary discussion aimed at evaluating the risk-benefit ratio of the treatment and taking into account several clinical, biochemical, and molecular factors. Age, performance status, and cancer-related symptoms are the most important clinical markers to be considered prior to starting MKI treatment, together with tumor burden. Some tissue and circulating biomarkers have been investigated, those involved in the angiogenic pathways being the most promising. Finally, prospective clinical trials aimed at evaluating predictive markers for therapeutic response are needed for tailoring patient management and allowing more appropriate treatment choices. Full article

The psoas-to-lumbar index (PLVI) has been reported as a simple and easy way to measure central sarcopenia. However, only few studies have evaluated the association between PLVI and survival in surgical patients. This study evaluated the association between preoperative PLVI and mortality in elderly patients who underwent hip fracture surgery. We retrospectively analyzed 615 patients who underwent hip fracture surgery between January 2014 and December 2018. The median value of each PLVI was calculated according to sex, and the patients were categorized into two groups on the basis of the median value (low PLVI group vs. high PLVI group). Cox regression analysis was performed to evaluate the risk factors for 1 year and overall mortalities. The median values of PLVI were 0.62 and 0.50 in men and women, respectively. In the Cox regression analysis, low PLVI was significantly associated with higher 1 year (hazard ratio (HR): 1.87, 95% confidence interval (CI): 1.18–2.96, p = 0.008) and overall mortalities (HR: 1.51, 95% CI: 1.12–2.03, p = 0.006). Low PLVI was significantly associated with a higher mortality. Therefore, PLVI might be an independent predictor of mortality in elderly patients undergoing hip fracture surgery. Full article

Ensuring multiple sclerosis (MS) patients’ adherence to therapy is often challenging, but it is crucial to their survival and health-related quality of life (HRQoL). The aim of the present study was to outline connections between adherence, physical and mental HRQoL, levels of psychological readiness to engage in a treatment, levels of social support, anthropometric, socio-demographic and clinical factors in patients suffering from MS. This cross-sectional study involved a sample of 237 Italian MS patients. A survey was conducted with a structured self-administered online questionnaire using validated measures of quality of life, adherence to therapy and anthropometric, socio-demographic, psychological and clinical variables. A path analysis was used to test the overall structure of the associations between the variables. The pathway indicates a positive association between mental health index and a stronger degree of engagement and being or having been in a long-term relationship. Physical health index was positively associated with age, having an occupation, and having a specific form of MS. Having had relapses in the previous year raised the odds of better adherence to therapy, while an increase in Body Mass Index (BMI) reduced them. Our findings could help in the management of MS patients, promoting behavioral interventions that take the psychological and socio-demographic peculiarities of each patient into account with a view to improving their adherence to therapy. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons (MNs) and severe muscle atrophy without effective treatment. Most research on ALS has been focused on the study of MNs and supporting cells of the central nervous system. Strikingly, the recent observations of pathological changes in muscle occurring before disease onset and independent from MN degeneration have bolstered the interest for the study of muscle tissue as a potential target for delivery of therapies for ALS. Skeletal muscle has just been described as a tissue with an important secretory function that is toxic to MNs in the context of ALS. Moreover, a fine-tuning balance between biosynthetic and atrophic pathways is necessary to induce myogenesis for muscle tissue repair. Compromising this response due to primary metabolic abnormalities in the muscle could trigger defective muscle regeneration and neuromuscular junction restoration, with deleterious consequences for MNs and thereby hastening the development of ALS. However, it remains puzzling how backward signaling from the muscle could impinge on MN death. This review provides a comprehensive analysis on the current state-of-the-art of the role of the skeletal muscle in ALS, highlighting its contribution to the neurodegeneration in ALS through backward-signaling processes as a newly uncovered mechanism for a peripheral etiopathogenesis of the disease. Full article

Oxaliplatin (OXA) is a platinum compound primarily used in the treatment of gastrointestinal cancer. OXA-induced peripheral neurotoxicity (OXAIPN) is the major non-hematological dose-limiting toxicity of OXA-based chemotherapy and includes acute transient neurotoxic effects that appear soon after OXA infusion, and chronic non-length dependent sensory neuronopathy symmetrically affecting both upper and lower limbs in a stocking-and-glove distribution. No effective strategy has been established to reverse or treat OXAIPN. Thus, it is necessary to early predict the occurrence of OXAIPN during treatment and possibly modify the OXA-based regimen in patients at high risk as an early diagnosis and intervention may slow down neuropathy progression. However, identifying which patients are more likely to develop OXAIPN is clinically challenging. Several objective and measurable early biomarkers for OXAIPN prediction have been described in recent years, becoming useful for informing clinical decisions about treatment. The purpose of this review is to critically review data on currently available or promising predictors of OXAIPN. Neurological monitoring, according to predictive factors for increased risk of OXAIPN, would allow clinicians to personalize treatment, by monitoring at-risk patients more closely and guide clinicians towards better counseling of patients about neurotoxicity effects of OXA. Full article

Current standard treatment of COVID-19 lacks in effective antiviral options. Plitidepsin, a cyclic depsipeptide authorized in Australia for patients with refractory multiple myeloma, has recently emerged as a candidate anti-SARS-CoV-2 agent. The aim of this review was to summarize current knowledge on plitidepsin’s clinical profile, anti-tumour and anti-SARS-CoV-2 mechanisms and correlate this with available or anticipated, preclinical or clinical evidence on the drug’s potential for COVID-19 treatment.PubMed, Scopus, CENTRAL, clinicaltrials.gov, medRxiv and bioRxiv databases were searched.Plitidepsinexerts its anti-tumour and antiviral properties primarily through acting on isoforms of the host cell’s eukaryotic-translation-elongation-factor-1-alpha (eEF1A). Through inhibiting eEF1A and therefore translation of necessary viral proteins, it behaves as a “host-directed” anti-SARS-CoV-2 agent. In respect to its potent anti-SARS-CoV-2 properties, the drug has demonstrated superior ex vivo efficacy compared to other host-directed agents and remdesivir, and it might retain its antiviral effect against the more transmittable B.1.1.7 variant. Its well-studied safety profile, also in combination with dexamethasone, may accelerate its repurposing chances for COVID-19 treatment. Preliminary findings in hospitalized COVID-19 patients, have suggested potential safety and efficacy of plitidepsin, in terms of viral load reduction and clinical resolution. However, the still incomplete understanding of its exact integration into host cell–SARS-CoV-2 interactions, its intravenous administration exclusively purposing it for hospital settings the and precocity of clinical data are currently considered its chief deficits. A phase III trial is being planned to compare the plitidepsin–dexamethasone regimen to the current standard of care only in moderately affected hospitalized patients. Despite plitidepsin’s preclinical efficacy, current clinical evidence is inadequate for its registration in COVID-19 patients.Therefore, multicentre trials on the drug’s efficacy, potentially also studying populations of emerging SARS-CoV-2 lineages, are warranted. Full article

In schizophrenia, social cognitive impairment is considered one of the greatest obstacles to social participation. Although numerous measures have been developed to assess social cognition, only a limited number of them have become available in Japan. We are therefore planning this evaluation study for social cognition measures in Japan (ESCoM) to confirm their psychometric characteristics and to promote research focused on social cognition. Participants in the cross-sectional observational study will be 140 patients with schizophrenia recruited from three Japanese facilities and 70 healthy individuals. In our primary analysis, we will calculate several psychometric indicators with a focus on whether they can independently predict social functioning. In secondary analyses, we will assess the reliability and validity of the Japanese translations of each measure and conduct an exploratory investigation of patient background, psychiatric symptoms, defeatist performance belief, and gut microbiota as determinants of social cognition. The protocol for this study is registered in UMIN-CTR, unique ID UMIN000043777. Full article

MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental carcinogens to lung cancer in 64 non-smokers living in Sicily and Catania city near to the Etna volcano. MicroRNAs were extracted from cancer lung biopsies, and from the surrounding lung normal tissue. The expression of 2549 human microRNAs was analyzed by microarray. Benzo(a)Pyrene-DNA adducts levels were analyzed in the patients’ blood by HPLC−fluorescence detection. Correlations between tetrols and environmental exposures were calculated using Pearson coefficients and regression variable plots. Compared with the healthy tissue, 273 microRNAs were downregulated in lung cancer. Tetrols levels were inversely related both with the distance from Etna and years since smoking cessation, but they were not significantly correlated to environmental exposures. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analyzed lung cancers in the following decreasing rank: (a) car traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to retrospectively investigate the contribution of environmental factors in human lung cancer occurring in non-smokers. Full article

Background: The substantial burden of kidney disease fosters interest in new ways of screening for early disease diagnosis, especially by non-invasive imaging. Increasing evidence for an association between retinal microvascular signs and kidney disease prompted us to investigate the relevant current literature on such an association systematically by performing a meta-analysis of our findings. Methods: We scrutinized the current literature by searching PubMed and Embase databases from for clinical studies of the association between retinal microvascular signs and prevalent or incident kidney disease. After excluding cases that did not meet our criteria, we extracted relevant data from 42 published studies (9 prospective, 32 cross-sectional, and 1 retrospective). Results: Our investigation yielded significant associations between retinal vascular changes (including retinopathy and retinal vascular diameter) and kidney dysfunction (including chronic kidney disease (CKD), end-stage renal disease (ESRD), albuminuria, and estimated glomerular filtration rate (eGFR) decline). According to our meta-analysis, retinopathy was associated with ESRD (hazard ratio (HR) 2.12 (95% confidence interval CI; 1.39–3.22)) and with CKD prevalence in the general population (odds ratio (OR) 1.31 (95% CI; 1.14–1.50)), and specifically in type 2 diabetic patients (OR 1.68 (95% CI; 1.68–2.16)). CRAE was associated with prevalent CKD (OR 1.41 (95% CI; 1.09–1.82)). Conclusions: Our findings suggest that the retinal microvasculature can provide essential data about concurrent kidney disease status and predict future risk for kidney disease development and progression. Full article

Worldwide, prostate cancer (PC) is the second-most-frequently diagnosed male cancer and the fifth-most-common cause of all cancer-related deaths. Suspicion of PC in a patient is largely based upon clinical signs and the use of prostate-specific antigen (PSA) levels. Although PSA levels have been criticised for a lack of specificity, leading to PC over-diagnosis, it is still the most commonly used biomarker in PC management. Unfortunately, PC is extremely heterogeneous, and it can be difficult to stratify patients whose tumours are unlikely to progress from those that are aggressive and require treatment intensification. Although PC-specific biomarker research has previously focused on disease diagnosis, there is an unmet clinical need for novel prognostic, predictive and treatment response biomarkers that can be used to provide a precision medicine approach to PC management. In particular, the identification of biomarkers at the time of screening/diagnosis that can provide an indication of disease aggressiveness is perhaps the greatest current unmet clinical need in PC management. Largely through advances in genomic and proteomic techniques, exciting pre-clinical and clinical research is continuing to identify potential tissue, blood and urine-based PC-specific biomarkers that may in the future supplement or replace current standard practices. In this review, we describe how PC-specific biomarker research is progressing, including the evolution of PSA-based tests and those novel assays that have gained clinical approval. We also describe alternative diagnostic biomarkers to PSA, in addition to biomarkers that can predict PC aggressiveness and biomarkers that can predict response to certain therapies. We believe that novel biomarker research has the potential to make significant improvements to the clinical management of this disease in the near future. Full article

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is associated with both obesity and type 2 diabetes. Our objective was to investigate the relation between DISH and visceral adipose tissue (VAT) in particular, as this would support a causal role of insulin resistance and low grade inflammation in the development of DISH. Methods: In 4334 patients with manifest vascular disease, the relation between different adiposity measures and the presence of DISH was compared using z-scores via standard deviation logistic regression analyses. Analyses were stratified by sex and adjusted for age, systolic blood pressure, diabetes, non-HDL cholesterol, smoking status, and renal function. Results: DISH was present in 391 (9%) subjects. The presence of DISH was associated with markers of adiposity and had a strong relation with VAT in males (OR: 1.35; 95%CI: 1.20–1.54) and females (OR: 1.43; 95%CI: 1.06–1.93). In males with the most severe DISH (extensive ossification of seven or more vertebral bodies) the association between DISH and VAT was stronger (OR: 1.61; 95%CI: 1.31–1.98), while increased subcutaneous fat was negatively associated with DISH (OR: 0.65; 95%CI: 0.49–0.95). In females, increased subcutaneous fat was associated with the presence of DISH (OR: 1.43; 95%CI: 1.14–1.80). Conclusion: Markers of adiposity, including VAT, are strongly associated with the presence of DISH. Subcutaneous adipose tissue thickness was negatively associated with more severe cases of DISH in males, while in females, increased subcutaneous adipose tissue was associated with the presence of DISH. Full article

Introduction: Image-based robotic assistance appears to be a promising tool for individualizing alignment in total knee arthroplasty (TKA). The patient-specific model of the knee enables a preoperative 3D planning of component position. Adjustments to the individual soft-tissue situation can be done intraoperatively. Based on this, we have established a standardized workflow to implement the idea of kinematic alignment (KA) for robotic-assisted TKA. In addition, we have defined limits for its use. If these limits are reached, we switch to a restricted KA (rKA). The aim of the study was to evaluate (1) in what percentage of patients a true KA or an rKA is applicable, (2) whether there were differences regarding knee phenotypes, and (3) what the differences of philosophies in terms of component position, joint stability, and early patient outcome were. Methods: The study included a retrospective analysis of 111 robotic-assisted primary TKAs. Based on preoperative long leg standing radiographs, the patients were categorized into a varus, valgus, or neutral subgroup. Initially, all patients were planned for KA TKA. When the defined safe zone had been exceeded, adjustments to an rKA were made. Intraoperatively, the alignment of the components and joint gaps were recorded by robotic software. Results and conclusion: With our indication for TKA and the defined boundaries, “only” 44% of the patients were suitable for a true KA with no adjustments or soft tissue releases. In the varus group, it was about 70%, whereas it was 0% in the valgus group and 25% in the neutral alignment group. Thus, significant differences with regard to knee morphotypes were evident. In the KA group, a more physiological knee balance reconstructing the trapezoidal flexion gap (+2 mm on average laterally) was seen as well as a closer reconstruction of the surface anatomy and joint line in all dimensions compared to rKA. This resulted in a higher improvement in the collected outcome scores in favor of KA in the very early postoperative phase. Full article

Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis. Germinomas are highly radiosensitive tumours, with survival rates >90% in the context of chemoradiotherapy. However, patients with resistant disease have limited therapeutic options and poor survival. The aim of this review is to highlight the genetic, epigenetic, and immunologic features, which could provide the basis for targeted therapy. Intracranial germinomas present genetic and epigenetic alterations (chromosomal aberrations, KIT, MAPK and PI3K pathways mutations, DNA hypomethylation, miRNA dysregulation) that may represent targets for therapy. Tyrosine kinase and mTOR inhibitors warrant further investigation in these cases. Immune markers, PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1), are expressed in germinomas, representing potential targets for immune checkpoint inhibitors. Resistant cases should benefit from a personalized management: genetic and immunological testing and enrolment in trials evaluating targeted therapies in intracranial germinomas. Full article

The objective of the study is to identify and evaluate possible factors that influence the ability to run before and after single event multi-level surgery (SEMLS). Young patients (6–25 years) with spastic cerebral palsy (GMFCSI-II) were retrospectively included. Type and number of surgical procedures, time for recovery and 3D gait analysis variables were analyzed with respect to the ability to run. In total, 98 patients (38 females; 60 males) who received SEMLS (12 years, SD 3.4) were included and compared to a control group of 71 conservatively treated patients. Of 60 runners pre-surgery, 17 (28%) lost the ability, while gained in 8 of 38 (21%) non-runners. The number of surgical procedures was a significant predictor and those who lost their ability to run had significantly more (mean = 5.9, SD = 1.7), compared to the patients who gained the ability (mean = 3.5, SD = 0.9). Further, pre-surgical function (e.g., gait speed) was significantly different (p < 0.001). Pre-surgical function and the number of surgical procedures seem to play an important role for the gain or loss of the ability to run after surgery. Caution is warranted in patients with lower pre-surgical function and the ability to run, as they seem at a higher risk to lose the ability. Full article

Endometrial cancer is one of the most common gynaecological malignancies worldwide. Histologically, two types of endometrial cancer with morphological and molecular differences and also therapeutic implications have been identified. Type I endometrial cancer has an endometrioid morphology and is estrogen-dependent, while Type II appears with non-endometrioid differentiation and follows an estrogen-unrelated pathway. Understanding the molecular biology and genetics of endometrial cancer is crucial for its prognosis and the development of novel therapies for its treatment. However, until now, scant attention has been paid to environmental components like the microbiome. Recently, due to emerging evidence that the uterus is not a sterile cavity, some studies have begun to investigate the composition of the endometrial microbiome and its role in endometrial cancer. In this review, we summarize the current state of this line of investigation, focusing on the relationship between gut and endometrial microbiome and inflammation, estrogen metabolism, and different endometrial cancer therapies. Full article

Introduction: Adverse effects on personalized care and outcomes of cardiovascular diseases (CVD) could occur if health systems do not work in an efficient manner. The pandemic caused by COVID-19 has opened new perspectives for the execution and advancement of cardiovascular tests through telemedicine platforms. Objective: This study aimed to analyze the usefulness of telemedical systems for providing personal care in the prevention of CVD. Methods: A systematic review analysis was conducted on the literature available from libraries such as PubMed (Medline), Scopus (Embase), and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Data available in the last 10 years (2011–2020) were also examined by PRISMA guidelines. The selected studies were divided into two categories: (1) benefits of telemedicine in CVD prevention, and (2) recent progress in telemedical services for personalized care of CVD. Results: The literature search produced 587 documents, and 19 articles were considered in this review. Results highlighted that the timely delivery of preventive care for CVD which can be implemented virtually can benefit and modify morbidity and mortality. This could also reduce the pressure on hospitals by decreasing acute CVD occurrence among the general population. The use of these technologies can also help to reduce access to hospitals and other medical devices when not necessary. Conclusions: Telemedicine platforms can be used for regular checkups for CVD and contribute to preventing the occurrence of acute events and more in general the progression of CVD. Full article

Patients with end-stage renal disease have a higher risk of cardiovascular morbidity and mortality. In this study, we investigated the predictive ability of a combination of cardiothoracic ratio (CTR) and aortic arch calcification (AoAC) for overall and cardiovascular mortality in patients receiving hemodialysis. We also evaluated the predictive power of AoAC and CTR for clinical outcomes. A total of 365 maintenance hemodialysis patients were included, and AoAC and CTR were measured using chest radiography at enrollment. We stratified the patients into four groups according to a median AoAC score of three and CTR of 50%. Multivariable Cox proportional hazards analysis was used to identify the risk factors of mortality. The predictive performance of the model for clinical outcomes was assessed using the χ2 test. Multivariable analysis showed that, compared to the AoAC < 3 and CTR < 50% group, the AoAC ≥ 3 and CTR < 50% group (hazard ratio [HR], 4.576; p < 0.001), and AoAC ≥ 3 and CTR ≥ 50% group (HR, 5.912; p < 0.001) were significantly associated with increased overall mortality. In addition, the AoAC < 3 and CTR ≥ 50% (HR, 3.806; p = 0.017), AoAC ≥ 3 and CTR < 50% (HR, 4.993; p = 0.002), and AoAC ≥ 3 and CTR ≥ 50% (HR, 8.614; p < 0.001) groups were significantly associated with increased cardiovascular mortality. Furthermore, adding AoAC and CTR to the basic model improved the predictive ability for overall and cardiovascular mortality. The patients who had a high AoAC score and cardiomegaly had the highest overall and cardiovascular mortality among the four groups. Furthermore, adding AoAC and CTR improved the predictive ability for overall and cardiovascular mortality in the hemodialysis patients. Full article

Breast magnetic resonance imaging (MRI) is currently a widely used clinical examination tool. Recently, MR diffusion-related technologies, such as intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI), have been extensively studied by breast cancer researchers and gradually adopted in clinical practice. In this study, we explored automatic tumor detection by IVIM-DWI. We considered the acquired IVIM-DWI data as a hyperspectral image cube and used a well-known hyperspectral subpixel target detection technique: constrained energy minimization (CEM). Two extended CEM methods—kernel CEM (K-CEM) and iterative CEM (I-CEM)—were employed to detect breast tumors. The K-means and fuzzy C-means clustering algorithms were also evaluated. The quantitative measurement results were compared to dynamic contrast-enhanced T1-MR imaging as ground truth. All four methods were successful in detecting tumors for all the patients studied. The clustering methods were found to be faster, but the CEM methods demonstrated better performance according to both the Dice and Jaccard metrics. These unsupervised tumor detection methods have the advantage of potentially eliminating operator variability. The quantitative results can be measured by using ADC, signal attenuation slope, D*, D, and PF parameters to classify tumors of mass, non-mass, cyst, and fibroadenoma types. Full article

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and exhibits an overall poor outcome. Due to the lack of targeted therapy, conventional systemic chemotherapy has been the main strategy for the treatment of TNBC. Further evidence has shown that combining radiation with chemotherapy is also a suitable treatment based on DNA repair deficiencies in patients with TNBC. However, the preferred treatment for metastatic TNBC remains unclear. Therefore, identification of biomarkers is an unmet need in personalized therapy for TNBC. RNF8 (ring finger protein 8) is a ubiquitin ligase implicated in TNBC metastasis; however, its role in TNBC pathogenesis is unclear. The purpose of the present study was to investigate the roles of the RNF8–CDH1(Cadherin 1) axis in node-positive TNBC patients. We found that the RNF8^high/CDH1^low index was significantly higher in patients with TNBC than in patients without TNBC. Furthermore, patients with an RNF8^high/CDH1^low index displayed poorer outcomes than those with an RNF8^low-medium/CDH1^medium-high index. Notably, as compared to patients with an RNF8^low-medium/CDH1^medium-high index, those with an RNF8^high/CDH1^low index had a poorer survival rate with chemotherapy treatment alone. The combination of radiation and chemotherapy resulted in a better survival rate than chemotherapy alone in patients with an RNF8^high/CDH1^low index. Taken together, the RNF8^high/CDH1^low index not only functions as a prognostic and therapeutic marker but may also act as a target in the development of anti-cancer agents for patients with TNBC. Full article

Breast Cancer (BC) is the leading cause of death due to cancer in women. Ensuring equitable, quality-assured and effective care has increased the complexity of BC management. This systematic review reports on the state-of-the art of available literature investigating the enactment of personalized treatment and patient-centered care models in BC clinical practice, building a framework for the delivery of personalized BC care within a Patient-Centered model. Databases were searched for articles (from the inception to December 2020) reporting on Patient-Centered or Personalized Medicine BC management models, assessing success factors or limits. Out of 1885 records, 25 studies were included in our analysis. The main success factors include clearly defined roles and responsibilities within a multi-professional collaboration, appropriate training programs and adequate communication strategies and adopting a universal genomic language to improve patients’ involvement in the decision-making process. Among detected barriers, delays in the use of genetic testing were linked to the lack of public reimbursement schemes and of clear indications in timing and appropriateness. Overall, both care approaches are complementary and necessary to effectively improve BC patient management. Our framework attempts to bridge the gap in assigning a central role played by shared decision-making, still scarcely investigated in literature. Full article

Personalized tongue pressure (TP) training focuses on improving swallowing. This study aims to establish the TP values of different age levels and compare changes between different swallowing status among community-dwelling elders. In this cross-sectional study, 1000 participants, aged 60 years old and above, were recruited from community care centers. All participants were classified into non chewing and/or swallowing difficulties (NCSD) and with chewing and/or swallowing difficulties (CSD) groups and their diseases and dieting status were recorded using a structured questionnaire. A disposable oral probe was used to measure TP by asking participants to compress it against the hard palate with maximum voluntary effort. Among 1000 elders, 63.10% had CSD and their TP (from 31.76 to 18.20 kPa) was lower than the NCSD group (from 33.56 to 24.51 kPa). Both groups showed the same tendency for TP decline with increasing age. Decline of TP makes CSD elderly have a poor appetite, eat a soft or liquid diet, and take longer to eat a meal (all p < 0.050). The secondary risk factor dominating TP decline for NCSD and CSD elders is having an education level less than primary school and an abnormal eating assessment, respectively. Our results demonstrated that TP decline has a significant relationship with age changes. Education level and an abnormal eating assessment score are closely associated with TP decline. A series of TP values can be used as a reference indicator of personalized medicine during the aging process among community-dwelling older adults. Full article