J. Pers. Med., Volume 13, Issue 10 (October 2023) – 99 articles

Motivation: Digital therapeutics (DTX), i.e., health interventions that are provided through digital means, are increasingly available for use; in some countries, physicians can even prescribe selected DTX following a reimbursement by health insurances. This results in an increasing need for methodologies to consider and monitor DTX’s negative consequences, their risks to patient safety, and possible adverse events. However, it is completely unknown which aspects should be subject to surveillance given the missing experiences with the tools and their negative impacts. Objective: Our aim is to develop a tool—the DTX Risk Assessment Canvas—that enables researchers, developers, and practitioners to reflect on the negative consequences of DTX in a participatory process. Method: Taking the well-established business model canvas as a starting point, we identified relevant aspects to be considered in a risk assessment of a DTX. The aspects or building blocks of the canvas were constructed in a two-way process: first, we defined the aspects relevant for discussing and reflecting on how a DTX might bring negative consequences and risks for its users by considering ISO/TS 82304-2, the scientific literature, and by reviewing existing DTX and their listed adverse effects. The resulting aspects were grouped into thematic blocks and the canvas was created. Second, six experts in health informatics and mental health provided feedback and tested the understandability of the initial canvas by individually applying it to a DTX of their choice. Based on their feedback, the canvas was modified. Results: The DTX Risk Assessment Canvas is organized into 15 thematic blocks which are in turn grouped into three thematic groups considering the DTX itself, the users of the DTX, and the effects of the DTX. For each thematic block, questions have been formulated to guide the user of the canvas in reflecting on the single aspects. Conclusions: The DTX Risk Assessment Canvas is a tool to reflect the negative consequences and risks of a DTX by discussing different thematic blocks that together constitute a comprehensive interpretation of a DTX regarding possible risks. Applied during the DTX design and development phase, it can help in implementing countermeasures for mitigation or means for their monitoring. Full article

One of the most promising advancements in healthcare is the application of digital twin technology, offering valuable applications in monitoring, diagnosis, and development of treatment strategies tailored to individual patients. Furthermore, digital twins could also be helpful in finding novel treatment targets and predicting the effects of drugs and other chemical substances in development. In this review article, we consider digital twins as virtual counterparts of real human patients. The primary aim of this narrative review is to give an in-depth look into the various data sources and methodologies that contribute to the construction of digital twins across several healthcare domains. Each data source, including blood glucose levels, heart MRI and CT scans, cardiac electrophysiology, written reports, and multi-omics data, comes with different challenges regarding standardization, integration, and interpretation. We showcase how various datasets and methods are used to overcome these obstacles and generate a digital twin. While digital twin technology has seen significant progress, there are still hurdles in the way to achieving a fully comprehensive patient digital twin. Developments in non-invasive and high-throughput data collection, as well as advancements in modeling and computational power will be crucial to improve digital twin systems. We discuss a few critical developments in light of the current state of digital twin technology. Despite challenges, digital twin research holds great promise for personalized patient care and has the potential to shape the future of healthcare innovation. Full article

Breast cancer is one of the main causes of death worldwide. Lately, there is great interest in developing methods that assess individual sensitivity and/or resistance of tumors to antineoplastics to provide personalized therapy for patients. In this study we used organotypic culture of human breast tumor slices to predict the experimental effect of antineoplastics on the viability of tumoral tissue. Samples of breast tumor were taken from 27 patients with clinically advanced breast cancer; slices were obtained and incubated separately for 48 h with paclitaxel, docetaxel, epirubicin, 5-fluorouracil, cyclophosphamide, and cell culture media (control). We determined an experimental tumor sensitivity/resistance (S/R) profile by evaluating tissue viability using the Alamar Blue^® metabolic test, and by structural viability (histopathological analyses, necrosis, and inflammation). These parameters were related to immunohistochemical expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The predominant histological type found was infiltrating ductal carcinoma (85.2%), followed by lobular carcinoma (7.4%) and mixed carcinoma (7.4%). Experimental drug resistance was related to positive hormone receptor status in 83% of samples treated with cyclophosphamide (p = 0.027). Results suggest that the tumor S/R profile can help to predict personalized therapy or optimize chemotherapeutic treatments in breast cancer. Full article

Background: Micronutrients are vital for general and oral health, and their potential anti-cancer properties are documented. We explore beneficial vitamins for oral potentially malignant disorders (OPMDs) and oral cancer (OC), assessing the therapeutic impacts of essential vitamin supplementation. Methods: We systematically review evidence on vitamin supplementation’s therapeutic effects for OPMDs and OC. Relevant studies were identified through comprehensive searches of MEDLINE, Evidence-Based Medicine, and Web of Science until 16 May 2023. All studies underwent risk of bias using criteria modified from the Office of Health Assessment and Translation (OHAT) tool. Results: We analysed 80 papers. Vitamin K, studied in vitro, shows promising therapeutic potential. Vitamin C, investigated in vivo (animals and humans), demonstrated mixed animal results and generally positive human trial effects. Vitamin A’s efficacy varied, with positive monotherapy or adjunct effects. Vitamins B and D showed therapeutic benefits. Oral cancer research was extensive, with a focus on oral lichen planus and oral leukoplakia among the 11 OPMDs. All bias levels were reported in ‘selective reporting’ and ‘performance’, except for “definitely high” in the ‘selection’, ‘detection’, and ‘attrition/exclusion’ domains. Conclusions: Evidence of vitamin interventions for OPMDs and OC ranges from mixed to promising. Standardizing the study design and outcomes would enhance future research. Full article

Introduction: Strokes continue to be considered public health problems due to the great social and health impact they entail. They are the second cause of death in the world, with a high incidence and prevalence. They are time-dependent diseases, and more than 80% of cases could be avoidable with greater management of risk factors. Objective: to analyze the factors that influence prehospital time in a stroke code. Assess the population’s knowledge of stroke symptoms and teach them how to act when a case is suspected. Document the continued training of health professionals for the early identification of patients with a suspected stroke. Demonstrate the importance of calling EMS as the first contact to reduce delays in prehospital time in a stroke. Methodology: A bibliographic review was carried out focusing on articles published between December 2014 and August 2023. The following databases were consulted: Pubmed (Medline), Dialnet, Google Scholar, Web of Science (WOS), Scielo, Scopus, and ScienceDirect. Results: After applying the article selection criteria and evaluating the quality of the methodology, a total of 18 articles were obtained. The results affirm that the importance of achieving a reduction in prehospital time is based mainly on knowledge of the symptoms and the use of new technologies. Conclusions: The evidence supports that the prehospital time of action in the stroke code is affected by numerous factors. These factors are determining factors in the time of action to achieve good effectiveness in the treatment of the pathology. Full article

This retrospective study aims to investigate the impact of cone-beam computed tomography (CBCT) viewing parameters such as contrast, slice thickness, and sharpness on the identification of the inferior alveolar nerve (IAC). A total of 25 CBCT scans, resulting in 50 IACs, were assessed by two investigators using a three-score system (good, average, and poor) on cross-sectional images. Slice thicknesses of 0.25 mm, 0.5 mm, and 1 mm were tested, along with varying sharpness (0, 6, 8, and 10) and contrast (0, 400, 800, and 1200) settings. The results were statistically analyzed to determine the optimal slice thickness for improved visibility of IAC, followed by evaluating the influence of sharpness and contrast using the optimal thickness. The identified parameters were then validated by performing semi-automated segmentation of the IACs and structure overlapping to evaluate the mean distance. Inter-rater and intra-rater reliability were assessed using Kappa statistics, and inferential statistics used Pearson’s Chi-square test. Inter-rater and intra-rater reliability for all parameters were significant, ranging from 69% to 83%. A slice thickness of 0.25 mm showed consistently “good” visibility (80%). Sharpness values of zero and contrast values of 1200 also demonstrated high frequencies of “good” visibility. Overlap analysis resulted in an average mean distance of 0.295 mm and a standard deviation of 0.307 mm across all patients’ sides. The study revealed that a slice thickness of 0.25 mm, zero sharpness value, and higher contrast value of 1200 improved the visibility and accuracy of IAC segmentation in CBCT scans. The individual patient’s characteristics, such as anatomical variations, decreased bone density, and absence of canal walls cortication, should be considered when using these parameters. Full article

This retrospective study aimed to: (1) investigate the surgical accuracy of maxillomandibular advancement (MMA) in obstructive sleep apnea (OSA) patients, with a specific focus on maxillary and mandibular advancement and counter-clockwise rotation and (2) investigate the correlation between the amount of achieved advancement and the reduction in the relative apnea hypopnea index (AHI). Sixteen patients, for whom a three-dimensional virtual surgical plan was generated preoperatively and a computed tomography scan (CT) or cone-beam computer tomography (CBCT) was acquired postoperatively, were included. The postoperative CT or CBCT was compared to the virtual surgical plan, and differences in the mandibular and maxillary advancement and counter-clockwise rotation were assessed. Maxillary and mandibular advancement (median 3.1 mm, p = 0.002 and 2.3 mm, p = 0.03, respectively) and counter-clockwise rotation (median 3.7°, p = 0.006 and 4.7°, p = 0.001, respectively) were notably less than intended. A significant correlation was found between the planned maxillary advancement and the difference between the planned and actual maxillary advancement (p = 0.048; adjusted R² = 0.1979) and also between the planned counter-clockwise rotation and the difference between the planned and actual counter-clockwise rotation for the mandible (p = 0.012; adjusted R² = 0.3261). Neither the maxilla-first nor the mandible-first surgical sequence proved to be superior in terms of the ability to achieve the intended movements (p > 0.45). Despite a significant reduction (p = 0.001) in the apnea hypopnea index (AHI) from a median of 62.6 events/h to 19.4 events/h following MMA, no relationship was found between the extent of maxillary or mandibular advancement and AHI improvement in this small cohort (p = 0.389 and p = 0.387, respectively). This study underlines the necessity for surgeons and future research projects to be aware of surgical inaccuracies in MMA procedures for OSA patients. Additionally, further research is required to investigate if sufficient advancement is an important factor associated with MMA treatment outcome. Full article

Background and objectives: Secondary prevention after acute coronary syndrome (ACS) is essential to reduce cardiovascular mortality and hospital readmission, ensuring patients return to normal with an improved quality of life. Thus, we investigate the benefits of a comprehensive cardiac rehabilitation (CR) program on lifestyle, risk factors and adherence to guideline-directed medical therapy (GDMT) in patients after ACS and myocardial revascularization through coronary artery by-pass grafting (CABG) or percutaneous coronary intervention (PCI). Methods: This is a prospective, longitudinal study in consecutive post-CABG or PCI patients after ACS that participated or not in a comprehensive CR. Cardiovascular risk factors, quality of life and adherence to GDMT were analyzed in terms of assessing the benefit of 12 months of comprehensive CR on reaching guidelines secondary prevention targets. Results: At the inclusion in comprehensive CR of all patients (n = 480), 85% had hypertension; 86% had elevated total cholesterol values; 69% were characterized by metabolic syndrome; 43% were obese; 31% were active smokers and 29% had type 2 diabetes mellitus. Only 26.66% (n = 128) followed the entire program for 12 months. No statistically significant differences in the prescription of GDMT at hospital discharge after myocardial revascularization between the CR (+) group (n = 128) versus CR (−) group (n = 352) (p > 0.05) were observed. After 12 moths, a significant adherence to GDMT in the CR (+) group vs. CR (−) group was recorded, as follows: antiplatelet agents (100% versus 96%, p = 0.001), beta-blockers (99% versus 92%, p = 0.02), ACE inhibitors/ARAB (89% versus 79%, p = 0.04), lipid-lowering drugs (100% versus 89%, p = 0.001). In total, 82% of the CR (+) patients had a significantly higher adherence at GDMT (82% versus 64%, p = 0.001). At 12 moths, the CR (+) group was characterized by significantly lower values than at the inclusion but some values still increased: systolic blood pressure (139.25 + 19.20 mmHg (p < 0.03)), total cholesterol (171.07 + 48.59 mg/dL (p = 0.0001)) and LDL-cholesterol (102.83 + 41.30 mg/dL (p = 0.009)). At the same time, the analysis of psychosocial factors using the HAD questionnaire revealed a statistically significant improvement in anxiety and depression scores: HAD-A score (9.1 ± 3.7 at T0 vs. 7.1 ± 4.2 at T1, p = 0.001) and HAD-D score (7.7 ± 3.19 at T0 vs. 6.4 ± 4.3 at T1, p = 0.003). A multivariable analysis, following GDMT, showed the actual value or information and training of patients regarding optimal cardiovascular risk factor control was independently associated with lower values of systolic blood pressure (R² = 0.48), diastolic (R² = 0.38), serum glucose (R² = 0.48), glycated hemoglobin (R² = 0.50), total cholesterol (R² = 0.31), LDL-cholesterol (R² = 0.30), HDL-cholesterol (R² = 0.19) and serum triglycerides (R² = 0.20). Conclusion: The twelve-month participation of post-ACS patients in comprehensive CR resulted in excellent post-revascularization management, as well as good adherence to guideline-directed medical therapy, provided further confirmation of the benefit of secondary prevention. Despite high adherence to drug treatments, targets for blood pressure, total cholesterol and LDL-cholesterol are inadequately achieved. Therefore, in the era of personalized medicine, patients with ACS should benefit from specific, comprehensive cardiovascular recovery programs that contain physiotherapists, psychologists, nutritionists and an experienced cardiologist in cardiovascular rehabilitation. Full article

In current practice, single-shot spinal anesthesia has traditionally been performed using the conventional surface-anatomic-Landmark-Guided technique. This “blind” technique has significant critical issues such as a high risk of complications due to the numerous attempts at spinal needle placement and the negative impact on the learning curve of the trainees. Ultrasound-Assisted spinal anesthesia could reduce these critical issues and allow trainees to perform the procedure more easily and with fewer complications for the patient. We performed a before-and-after monocentric retrospective comparative study at the University of Naples “Federico II” (Naples, Italy). Inclusion criteria were as follows: patients aged 18 years or older; ASA physical status between I and IV; and elective orthopedic surgery under single-shot spinal anesthesia performed by supervised trainees between January 2022 and December 2022. In the selected cohort, 88 patients were included in group A (Landmark-Guided spinal anesthesia) and 91 in group B (Ultrasound-Assisted spinal anesthesia). The number of attempts by trainees (p-value < 0.005), procedure performing time (<0.001), and patient discomfort (<0.001) were significantly lower in group B than in group A. Ultrasound-Assisted single-shot spinal anesthesia performed by novice trainees reduces the number of attempts, complication rate, periprocedural pain, and patient discomfort. Full article

Background: Irradiation plays an important role in the oncological treatment of various tumor entities. The aim of the study was to investigate the influence of different irradiation regimens on random-pattern flaps at the molecular and histopathological levels. Methods: Twenty-five rats underwent harvesting of bilateral random-pattern fasciocutaneous flaps. The right flaps received irradiation, while the left flaps served as non-irradiated intraindividual controls. Five rats served as a non-irradiated control group. Four different irradiation regimens with give rats each were tested: 20 Gy postoperatively, 3 × 12 Gy postoperatively, 20 Gy preoperatively, and 3 × 12 Gy preoperatively. Two weeks after surgery, HE staining and immunohistochemical staining for CD68 and ERG, as well as PCR analysis to detect Interleukin 6, HIF-1α, and VEGF, were performed. Results: A postoperative cumulative higher dose of irradiation appeared to result in an increase in necrosis, especially in the superficial layers of the flap compared to preoperative or single-stage irradiation. In addition, we observed increased expression of VEGF and HIF-1α in all irradiation groups. Conclusion: Even though no statistically significant differences were found between the different groups, there was a tendency for fractional postoperative irradiation with a higher total dose to have a more harmful effect compared to preoperative or single-dose irradiation. Full article

Autism spectrum disorder (ASD), characterized by social, communication, and behavioral abnormalities, affects 1 in 36 children according to the CDC. Several co-occurring conditions are often associated with ASD, including sleep and immune disorders and gastrointestinal (GI) problems. ASD is also associated with sensory sensitivities. Some individuals with ASD exhibit episodes of challenging behaviors that can endanger themselves or others, including aggression and self-injurious behavior (SIB). In this work, we explored the use of artificial intelligence models to predict behavior episodes based on past data of co-occurring conditions and environmental factors for 80 individuals in a residential setting. We found that our models predict occurrences of behavior and non-behavior with accuracies as high as 90% for some individuals, and that environmental, as well as gastrointestinal, factors are notable predictors across the population examined. While more work is needed to examine the underlying connections between the factors and the behaviors, having reasonably accurate predictions for behaviors has the potential to improve the quality of life of some individuals with ASD. Full article

The role of nutrition in the management of asthma in obese patients is of increasing interest due to their limited response to inhaled corticosteroids. Some studies note that through diet and lifestyle, there can be an improvement in asthma control. The aim of the present study was to investigate the adherence to the Mediterranean Diet and its association with asthma severity and quality of life in patients with bronchial asthma. This is a cross-sectional study of 85 patients (70.6% female), with a mean age of 57 years, from the General University Hospital of Larissa and, more specifically, patients of the outpatient asthma clinic. Data were collected with the use of specific questionnaires. In relation to BMI, 12.9% of participants were of a normal weight, 45.9% were overweight, 25.9% were obese level I, 5.9% were obese level II, and 9.4% were in the morbidly obese range. Based on the Med Diet Score (ranging from 21 to 35), most participants (85.9%) reported moderate adherence to the Mediterranean Diet. Further analysis examined the correlations of the PCS-12 score with the frequency of consumption of each of the 11 food categories, as well as all demographic and health behavior variables. The ranked correlations indicated a significant relationship between PCS-12 score and Med Diet adherence and the consumption of alcoholic beverages (r = 0.437, p < 0.05), in accordance with the Mediterranean Diet suggestions, as well as a negative relationship with BMI score (r = −0.454, p < 0.010). Moreover, significant correlations were also present between the physical quality of life and AQLQ score and work type, as well as gender, age, and marital status. The results of our study showed a high rate of obesity in patients with asthma at the General University Hospital of Larissa and moderate adherence to the Mediterranean Diet. Increased BMI and alcoholic beverage consumption in asthma patients were significant predictors of lower physical health-related quality of life. In conclusion, personal and society-level interventions are required to effectively address obesity and poor diet in patients with asthma. Full article

Background: Therapeutic exercise (TE) recommendations for non-specific low back pain (LBP) are meant to support therapy choices for people who suffer from this condition. The aim of this study was to reach an agreement on the definition and use of TE in the care of people with LBP. Methods: A Delphi study was carried out with a formal consensus procedure and sufficient scientific evidence, using an established methodology. Four rounds of anonymous questionnaires were administered to create useful suggestions and instructions in terms of the therapeutic activity for patients with LBP, and a group consensus conference. Results: A consensus was reached on most of the questions after 35 physiotherapists completed the questionnaires. Participants agreed that proper TE requires correct posture, body awareness, breathing, movement control, and instruction. Patients with LBP were advised to participate in supervised sessions twice a week for 30 to 60 min for a period of 3 to 6 months. Participants added that tailored evaluation and exercise prescription, monitoring, and functional integration of exercise, as well as using specific equipment, would benefit patients with LBP. Conclusions: TE recommendations for patients with LBP should be dosed and customized based on their personal psychological needs, level of fitness, and kinesiophobia. Full article

Myocardial bridging (MB) is a congenital coronary artery anomaly and an important cause of angina. The genetic basis of MB is currently unknown. This study used a whole-exome sequencing technique and analyzed genotypic differences. Eight coronary angiography-confirmed cases of severe MB and eight age- and sex-matched control patients were investigated. In total, 139 rare variants that are potentially pathogenic for severe MB were identified in 132 genes. Genes with multiple rare variants or co-predicted by ClinVar and CADD/REVEL for severe MB were collected, from which heart-specific genes were selected under the guidance of tissue expression levels. Functional annotation indicated significant genetic associations with abnormal skeletal muscle mass, cardiomyopathies, and transmembrane ion channels. Candidate genes were reviewed regarding the functions and locations of each individual gene product. Among the gene candidates for severe MB, rare variants in DMD, SGCA, and TTN were determined to be the most crucial. The results suggest that altered anchoring proteins on the cell membrane and intracellular sarcomere unit of cardiomyocytes play a role in the development of the missed trajectory of coronary vessels. Additional studies are required to support the diagnostic application of cardiac sarcoglycan and dystroglycan complexes in patients with severe MB. Full article

Endoscopic surgery of the cervical spine is constantly evolving and the spectrum of its indications has expanded in recent decades. Full-endoscopic techniques have standardized the procedures for posterior and anterior access. The full-endoscopic approach was developed to treat degenerative diseases with the least possible invasion and without causing instability of the cervical spine. The posterior full-endoscopic approach is indicated for the treatment of diseases of the lateral part of the vertebral segment, such as herniations and stenoses of the lateral recess and vertebral foramen. There has been little discussion of this approach to the treatment of central stenosis of the cervical spine. This technical note describes a step-by-step surgical technique for central and over-the-top full-endoscopic decompression in the cervical spine, using a 3.7 mm working channel endoscope. This technique has already been shown to be effective in a recent case series with a 4.7 mm working channel endoscope, and may represent a new treatment option for central or bilateral lateral recess stenosis. There is also the possibility of a bilateral full-endoscopic approach, but this may be associated with greater muscle damage and a longer operative time. Case series and comparative studies should be encouraged to confirm the safety and utility of this technique. Full article

Non-invasive scar management typically involves pressure therapy, hydration with silicones or moisturizers, and UV protection. Moisture loss from scars can lead to hypertrophic scar formation. Pressure therapy reduces blood flow, fibroblast activity, and transforming growth factor beta 1 (TGF-β1) release. This study examined various moisturizers and liquid silicone gel’s impact on microcirculation. 40 volunteers participated in a study where superficial abrasions were created to induce trans epidermal water loss (TEWL). Five moisturizers (TEDRA^®, TEDRA^® NT1, TEDRA^® NT3, Alhydran^®, Lipikar^®) and BAP Scar Care^® silicone gel were tested. TEWL, hydration, and blood flow were measured up to 4 h post-application. Results showed that silicone had the least impact on occlusion and hydration. Alhydran^® reduced blood flow the most, while Lipikar^® increased it the most. TEDRA^® NT1 had reduced flow compared to TEDRA^® and TEDRA^® NT3. All TEDRA^® products exhibited high hydration, and all but silicone showed good occlusion. Moisturizers influenced skin microcirculation, with some causing decrease, while others increased flow. However, the clinical impact on scarring remains unclear compared to the evident effects of hydration and occlusion. More research is necessary to study moisturizers alone and with pressure therapy on scars, along with potential adverse effects of increased microcirculation on scars. Full article

Patients undergoing coronary revascularization with extracorporeal circulation or cardiopulmonary bypass (CPB) may develop several biochemical changes in the microcirculation that lead to a systemic inflammatory response. Surgical incision, post-CPB reperfusion injury and blood contact with non-endothelial membranes can activate inflammatory signaling pathways that lead to the production and activation of inflammatory cells, with cytokine production and oxidative stress. This inflammatory storm can cause damage to vital organs, especially the heart, and thus lead to complications in the postoperative period. In addition to the organic pathophysiology during and after the period of exposure to extracorporeal circulation, this review addresses new perspectives for intraoperative treatment and management that may lead to a reduction in this inflammatory storm and thereby improve the prognosis and possibly reduce the mortality of these patients. Full article

Current research primarily emphasizes the generalized correlations between airborne pollution and respiratory diseases, seldom considering the differential impacts of particular particulate matter sizes on chronic obstructive pulmonary disease (COPD) exacerbations in distinct Global Initiative for Obstructive Lung Disease (GOLD) categories. This study hypothesizes a critical association between particulate matter sizes (PM 1.0, PM 2.5, and PM 10) and exacerbation frequency in COPD patients categorized under GOLD 3 and GOLD 4, with a potential augmenting role played by proximity to main roads and industrial areas. This research aspires to offer a nuanced perspective on the exacerbation patterns in these groups, setting the stage for targeted intervention strategies. Utilizing a prospective design, this study followed 79 patients divided into GOLD 3 (n = 47) and GOLD 4 (n = 32) categories. The participants were monitored for ten days for daily activity levels, symptoms, living conditions, and airborne particulate matter concentrations, with spirometric evaluations employed to measure lung function. Statistical analyses were used to identify potential risk factors and significant associations. The analysis revealed substantial disparities in airborne particulate matter sizes between the two groups. The mean PM 1.0 concentration was notably higher in GOLD 4 patients (26 µg/m³) compared to GOLD 3 patients (18 µg/m³). Similarly, elevated PM 2.5 levels were observed in the GOLD 4 category (35 µg/m³) in contrast to the GOLD 3 category (24 µg/m³). A vital finding was the increased frequency of exacerbations in individuals residing within 200 m of main roads compared to those living further away (OR = 2.5, 95% CI: 1.5–4.1). Additionally, patients residing in homes smaller than 50 square meters demonstrated a greater frequency of exacerbations. Spirometry results corroborated the exacerbated condition in GOLD 4 patients, indicating a significant decline in lung function parameters compared to the GOLD 3 group. This study substantiates a significant association between airborne particulate matter sizes and exacerbation frequencies in COPD patients, particularly accentuating the increased risk in GOLD 4 patients. Our findings underscore the pivotal role of environmental factors, including the size of living areas and proximity to main roads, in influencing COPD exacerbations. These results suggest the need for personalized healthcare strategies and interventions, which account for environmental risk factors and the distinctions between GOLD 3 and GOLD 4 categories of COPD patients. Full article

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed βIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger βIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and βIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility. Full article

The relationship between spinal alignment, particularly degenerative thoracolumbar kyphosis (DTLK) combined with lumbar spine stenosis (LSS), and paraspinal muscle content remains underexplored. This study aimed to elucidate the characteristics of paraspinal muscle distribution in DTLK patients and its association with lumbar lordosis (LL) and body mass index (BMI). Methods: A case–control study was conducted comparing 126 patients with DTLK and LSS against 87 control patients. The lumbar crossing indentation value (LCIV) was introduced as a novel measurement for paraspinal muscle content, and its relationship with thoracolumbar kyphosis (TLK), BMI, and LL was assessed. Results: LCIV in DTLK patients was found to be lower than in the control group, with a progressive increase from the upper to lower lumbar spine. In the control group, paraspinal muscle content was observed to increase with age and BMI, and LCIV was higher in males. However, the DTLK group showed no gender difference. LCIV in the DTLK group was more pronounced in patients with increased LL. The degree of TLK was not influenced by BMI but was associated with the content of the paravertebral muscle. Conclusions: Paraspinal muscle content, as measured by LCIV, is significantly associated with DTLK and LSS. The study emphasizes the importance of considering paraspinal muscle health in DTLK patients and offers valuable insights for diagnosis and therapeutic interventions. Full article

With the recent diffusion of access to publicly available large language models (LLMs), common interest in generative artificial-intelligence-based applications for medical purposes has skyrocketed. The increased use of these models by tech-savvy patients for personal health issues calls for a scientific evaluation of whether LLMs provide a satisfactory level of accuracy for treatment decisions. This observational study compares the concordance of treatment recommendations from the popular LLM ChatGPT 3.5 with those of a multidisciplinary tumor board for breast cancer (MTB). The study design builds on previous findings by combining an extended input model with patient profiles reflecting patho- and immunomorphological diversity of primary breast cancer, including primary metastasis and precancerous tumor stages. Overall concordance between the LLM and MTB is reached for half of the patient profiles, including precancerous lesions. In the assessment of invasive breast cancer profiles, the concordance amounts to 58.8%. Nevertheless, as the LLM makes considerably fraudulent decisions at times, we do not identify the current development status of publicly available LLMs to be adequate as a support tool for tumor boards. Gynecological oncologists should familiarize themselves with the capabilities of LLMs in order to understand and utilize their potential while keeping in mind potential risks and limitations. Full article

The increase in the prevalence of overweight, obesity and associated diseases is a serious problem. The aim of the study was to identify rare variants in obesity-associated genes in young adults with abdominal obesity in our population and to analyze information about these variants in other populations. Targeted high-throughput sequencing of obesity-associated genes was performed (203 young adults with an abdominal obesity phenotype). In our study, all of the 203 young adults with abdominal obesity had some rare variant in the genes associated with obesity. The widest range of rare and common variants was presented in ADIPOQ, FTO, GLP1R, GHRL, and INS genes. The use of targeted sequencing and clinical criteria makes it possible to identify carriers of rare clinically significant variants in a wide range of obesity-associated genes and to investigate their influence on phenotypic manifestations of abdominal obesity. Full article

Ewing Sarcoma (ES) is an aggressive, mesenchymal malignancy associated with a poor prognosis in the recurrent or metastatic setting with an estimated overall survival (OS) of <30% at 5 years. ES is characterized by a balanced, reciprocal chromosomal translocation involving the EWSR1 RNA-binding protein and ETS transcription factor gene (EWS-FLI being the most common). Interestingly, murine ES models have failed to produce tumors phenotypically representative of ES. Genomic alterations (GA) in ES are infrequent and may work synergistically with EWS-ETS translocations to promote oncogenesis. Aberrations in fibroblast growth factor receptor (FGFR4), a receptor tyrosine kinase (RTK) have been shown to contribute to carcinogenesis. Mouse embryonic fibroblasts (MEFs) derived from knock-in strain of homologous Fgfr4G385R mice display a transformed phenotype with enhanced TGF-induced mammary carcinogenesis. The association between the FGFRG388R SNV in high-grade soft tissue sarcomas has previously been demonstrated conferring a statistically significant association with poorer OS. How the FGFR4G388R SNV specifically relates to ES has not previously been delineated. To further define the genomic landscape and corresponding pathway alterations in ES, comprehensive genomic profiling (CGP) was performed on the tumors of 189 ES patients. The FGFR4G388R SNV was identified in a significant proportion of the evaluable cases (n = 97, 51%). In line with previous analyses, TP53 (n = 36, 19%), CDK2NA/B (n = 33, 17%), and STAG2 (n = 22, 11.6%) represented the most frequent alterations in our cohort. Co-occurrence of CDK2NA and STAG2 alterations was observed (n = 5, 3%). Notably, we identified a higher proportion of TP53 mutations than previously observed. The most frequent pathway alterations affected MAPK (n = 89, 24% of pathological samples), HRR (n = 75, 25%), Notch1 (n = 69, 23%), Histone/Chromatin remodeling (n = 57, 24%), and PI3K (n = 64, 20%). These findings help to further elucidate the genomic landscape of ES with a novel investigation of the FGFR4G388R SNV revealing frequent aberration. Full article

Primary lung cancer is a devastating disease with high morbidity and mortality rates. Patients with a previous oncological history may present with multiple comorbidities, unique clinical features, and unique outcomes after surgical intervention for primary lung cancer. This study aimed to compare the clinical features and outcomes of patients with a previous oncological history who underwent video-assisted thoracoscopic surgery (VATS) or open surgery (OS) for primary lung cancer. A retrospective analysis was conducted on 84 patients with a previous oncological history who underwent surgical intervention for primary lung cancer between January 2018 and January 2023. Among them, 55 patients underwent VATS, while 29 patients underwent OS. Demographic and clinical characteristics, perioperative variables, and postoperative outcomes of the two surgical groups were collected and compared. Most of the 84 patients were women (58.4%) with a high smoking prevalence (44.1%) and a median of 32.3 packs-year. The patients’ histories were most predominant for gynecologic cancers (44.4%) and colorectal cancers (18.6%). The results showed that the VATS group had a significantly shorter median hospital stay than the OS group (6.0 days vs. 12.0 days, p-value < 0.001). Additionally, the VATS group had lower incidences of air leaks 24 h post-surgery (12.7% vs. 48.3%, p-value < 0.001) and intractable pain (3.6% vs. 17.2%, p-value = 0.031), as well as significantly lower operative times (270 min vs. 350 min, p-value = 0.046). However, there were no significant differences between the VATS and OS groups in overall survival (log-rank p-value = 0.447). Furthermore, although the 3-month survival was significantly higher in the VATS group (98.2% vs. 79.3%, p-value = 0.003), only one patient from the VATS group (1.8%) and two patients from the OS group (6.9%) were still alive five years after the intervention. In conclusion, VATS is a safe and effective surgical option for patients with a previous oncological history who require surgical intervention for primary lung cancer, with shorter operative times, shorter hospital stays, and lower rates of complications compared to those of OS patients, without compromising oncological outcomes. Nevertheless, both surgical options failed to improve the 5-year survival rate, probably due to the high prevalence of comorbidities and the burden of previous cancer in this population. Full article

Spontaneous pneumothorax and pneumomediastinum (SP–SPM) are relatively rare medical conditions that can occur with or independently of COVID-19. We conducted a retrospective analysis of SP–SPM cases presented to the emergency departments (EDs) of two University-affiliated tertiary hospitals from 1 March 2020 to 31 October 2022. A total of 190 patients were identified: 52 were COVID-19 cases, and 138 were non-COVID-19 cases. The primary outcome we were looking for was in-hospital mortality. The secondary outcomes concerned the disease severity assessed by (a) days of hospitalization; (b) required mechanical ventilation (MV); and (c) required intensive care (IC). All were investigated in the context of the five pandemic waves and the patients’ age and comorbidities. The pandemic waves had no significant effect on the outcomes of these patients. Logistic regression found age (OR = 1.043; 95%CI 1.002–1.085), COVID-19 (OR = 6.032; 95%CI 1.757–20.712), number of comorbidities (OR = 1.772; 95%CI 1.046–3.001), and ground-glass opacities over 50% (OR = 5.694; 95%CI 1.169–27.746) as significant risk predictors of in-hospital death while controlling for gender, smoking, the pandemic wave, and the extension of SP–SPM. The model proved good prediction performance (Nagelkerke R-square = 0.524) and would hold the same significant predictors for MV and IC. Full article

Multimodal neuroimaging has gained traction in Alzheimer’s Disease (AD) diagnosis by integrating information from multiple imaging modalities to enhance classification accuracy. However, effectively handling heterogeneous data sources and overcoming the challenges posed by multiscale transform methods remains a significant hurdle. This article proposes a novel approach to address these challenges. To harness the power of diverse neuroimaging data, we employ a strategy that leverages optimized convolution techniques. These optimizations include varying kernel sizes and the incorporation of instance normalization, both of which play crucial roles in feature extraction from magnetic resonance imaging (MRI) and positron emission tomography (PET) images. Specifically, varying kernel sizes allow us to adapt the receptive field to different image characteristics, enhancing the model’s ability to capture relevant information. Furthermore, we employ transposed convolution, which increases spatial resolution of feature maps, and it is optimized with varying kernel sizes and instance normalization. This heightened resolution facilitates the alignment and integration of data from disparate MRI and PET data. The use of larger kernels and strides in transposed convolution expands the receptive field, enabling the model to capture essential cross-modal relationships. Instance normalization, applied to each modality during the fusion process, mitigates potential biases stemming from differences in intensity, contrast, or scale between modalities. This enhancement contributes to improved model performance by reducing complexity and ensuring robust fusion. The performance of the proposed fusion method is assessed on three distinct neuroimaging datasets, which include: Alzheimer’s Disease Neuroimaging Initiative (ADNI), consisting of 50 participants each at various stages of AD for both MRI and PET (Cognitive Normal, AD, and Early Mild Cognitive); Open Access Series of Imaging Studies (OASIS), consisting of 50 participants each at various stages of AD for both MRI and PET (Cognitive Normal, Mild Dementia, Very Mild Dementia); and whole-brain atlas neuroimaging (AANLIB) (consisting of 50 participants each at various stages of AD for both MRI and PET (Cognitive Normal, AD). To evaluate the quality of the fused images generated via our method, we employ a comprehensive set of evaluation metrics, including Structural Similarity Index Measurement (SSIM), which assesses the structural similarity between two images; Peak Signal-to-Noise Ratio (PSNR), which measures how closely the generated image resembles the ground truth; Entropy (E), which assesses the amount of information preserved or lost during fusion; the Feature Similarity Indexing Method (FSIM), which assesses the structural and feature similarities between two images; and Edge-Based Similarity (EBS), which measures the similarity of edges between the fused and ground truth images. The obtained fused image is further evaluated using a Mobile Vision Transformer. In the classification of AD vs. Cognitive Normal, the model achieved an accuracy of 99.00%, specificity of 99.00%, and sensitivity of 98.44% on the AANLIB dataset. Full article

Background: Intraoral orthodontic elastics (IOE), typically referred to as rubber bands, are important tools for correcting malocclusion, and they are classified into latex and synthetic (elastomeric-based) elastics. They have different strengths and sizes, depending on their intended use, that provide clinicians with the ability to correct both anteroposterior and vertical discrepancies. Clinical use, together with saliva, alters the physical characteristics of both latex and synthetic elastics, causing declines in strength over time. Aim: The aim of the study was to assess, through a systematic review of in vitro studies, the properties of intraoral elastics. The primary goal was to evaluate how IOEs behave in terms of tension strength and duration. The secondary goal was to investigate the force loss during the first hours of wear. The tertiary goal was to assess how these forces decayed. Materials and methods: The following electronic databases were searched from December 2020 to April 2021: Medline Full Text, PubMed, Cochrane Clinical Trials Register, Science Direct, and Literature Review. Out of 8505 initial articles, 10 were selected for the systematic review. Results: The force-degradation property was found in all types of IOEs. The loss of strength was directly proportional to time, with the highest value during the first 3 h after extension, regardless of the elastic band size and manufacturer. The forces generated by the latex bands were higher than in those of the elastomeric-based elastics, but they did not consistently correspond to the loads specified by the manufacturers. The retention forces in the latex IOEs were significantly higher than those in the nonlatex bands, suggesting that elastomeric-based bands need to be changed more frequently and at regular intervals throughout a 24 h period. Conclusion: This systematic review indicates that intraoral orthodontic elastics have the greatest loss of force during the first 3 h, that latex rubber bands have the highest strength during the first hour, that the forces generated are not always consistent with the manufacturer’s specifications, and that nonlatex (elastomeric-based) IOEs need to be changed frequently and regularly during a 24-h cycle. Full article

Hereditary conditions that affect tooth enamel in quantity and/or quality are called amelogenesis imperfecta (AI). AI can occur as an isolated condition or as a symptom of a syndrome. An OMIM search with the term “AI” yielded 79 result entries. Mutations in the same gene cause syndromic or non-syndromic AI, depending on the nature of the mutations. In this study, we recruited two AI families and performed mutational analysis using whole-exome sequencing. The proband of family 1, with hypoplastic pitted AI and mild localized atopic dermatitis, had compound heterozygous COL17A1 mutations (paternal NM_000494.4: c.3598G>T, p.Asp1200Tyr and maternal c.1700G>A, p.Gly567Glu). The proband of family 2, with hypoplastic pitted AI and Jervell and Lange-Nielsen syndrome, had a recurrent LAMB3 mutation (NM_000228.3: c.3463_3475del, p.(Glu1155Thrfs*51)) in addition to compound heterozygous mutations in the KCNQ1 gene. Full article