J. Pers. Med., Volume 14, Issue 1 (January 2024) – 126 articles

Despite the increased frequency of endometriosis, it remains one of the most enigmatic disorders regarding its effects on pregnancy. Endometriosis adversely affects both natural and assisted conception. Impaired folliculogenesis, which causes follicular dysfunction and low egg quality, as well as luteal phase problems, reduced fertilization, and abnormal embryogenesis, are some of the mechanisms advocated to explain reproductive dysfunction. There is a rising need for a comprehensive study of the potential negative consequences of this condition on pregnancy outcomes, including the postpartum period, as more women with a medical history of endometriosis become pregnant. Obstetrical complications (small for gestational age [SGA], cesarean section [CS], miscarriage, hemorrhage, low placental adhesion, and preterm delivery) are statistically elevated in women with endometriosis. Furthermore, ruptured ovarian endometrioma, appendicitis, intestinal perforation, and hemoperitoneum have been described in pregnancy. Obstetricians are largely unfamiliar with these complications, as they have not been thoroughly investigated. The development and pathogenesis of endometriosis is an important field of study and has not yet been fully elucidated. Finding these mechanisms is crucial for the development of new and more effective strategies to treat this condition. Endometriosis can have an impact on obstetric and neonatal outcomes of pregnancy, in addition to its potential effects on conception. To date, no additional monitoring is recommended for pregnancies with a history of endometriosis. However, more studies are urgently needed to assess the need for the tailored pregnancy monitoring of women with endometriosis. Full article

Purpose: The treatment of childhood myopia often involves the use of topical atropine, which has been demonstrated to be effective in decelerating the progression of myopia. It is crucial to monitor intraocular pressure (IOP) to ensure the safety of topical atropine. This study aims to identify the optimal machine learning IOP-monitoring module and establish a precise baseline IOP as a clinical safety reference for atropine medication. Methods: Data from 1545 eyes of 1171 children receiving atropine for myopia were retrospectively analyzed. Nineteen variables including patient demographics, medical history, refractive error, and IOP measurements were considered. The data were analyzed using a multivariate adaptive regression spline (MARS) model to analyze the impact of different factors on the End IOP. Results: The MARS model identified age, baseline IOP, End Spherical, duration of previous atropine treatment, and duration of current atropine treatment as the five most significant factors influencing the End IOP. The outcomes revealed that the baseline IOP had the most significant effect on final IOP, exhibiting a notable knot at 14 mmHg. When the baseline IOP was equal to or exceeded 14 mmHg, there was a positive correlation between atropine use and End IOP, suggesting that atropine may increase the End IOP in children with a baseline IOP greater than 14 mmHg. Conclusions: MARS model demonstrates a better ability to capture nonlinearity than classic multiple linear regression for predicting End IOP. It is crucial to acknowledge that administrating atropine may elevate intraocular pressure when the baseline IOP exceeds 14 mmHg. These findings offer valuable insights into factors affecting IOP in children undergoing atropine treatment for myopia, enabling clinicians to make informed decisions regarding treatment options. Full article

Background: Dyslipidemia is a known risk factor for cardiac dysfunction, and lipid-lowering therapy with statins reduces symptoms and reduces hospitalization related to left ventricular heart failure. Acute myocardial infarction (AMI) is a cause of morbidity and mortality worldwide. In this study, we aimed to determine the real-world AMI treatment drug combination used in Taiwan by using the NHI database to understand the treatment outcomes of current clinical medications prescribed for hyperlipidemia patients with AMI. Methods: Using the NHI Research Database (NHIRD), we conducted a retrospective cohort study that compared different treatments for AMI in hyperlipidemia patients in the period from 2016 to 2018. We compared the survival outcomes between those treated with and without organic nitrates in this cohort. Results: We determined that most hyperlipidemia patients were aged 61–70 y (29.95–31.46% from 2016 to 2018), and the annual AMI risk in these patients was <1% (0.42–0.68% from 2016 to 2018). The majority of hyperlipidemia patients with AMI were women, and 25.64% were aged 61–70 y. Receiving organic nitrates was associated with lower all-cause mortality rates (HR, 95% CI, p-value = 0.714, 0.674–0.756, p < 0.0001). After multivariate analysis, the overall survival in four groups (beta-blockers, beta-blocker + diuretics, diuretics, and others) receiving an organic nitrate treatment was significantly higher than in the groups that were not treated with organic nitrates (beta-blockers HR = 0.536, beta-blocker + diuretics HR = 0.620, diuretics HR = 0.715, and others HR = 0.690). Conclusions: The survival benefit was significantly greater in patients treated with organic nitrates than in those treated without organic nitrates, especially when combined with diuretics. A combination of organic nitrates could be a better treatment option for hyperlipidemia patients with AMI. Full article

Dysautonomias are conditions in which altered functions of one or more components of the autonomic nervous system (ANS) adversely affect health. This essay is about how elucidating mechanisms of dysautonomias may rationalize personalized treatments. Emphasized here are two relatively new ideas—the “extended” autonomic system (EAS) and the “homeostat” theory as applied to the pathophysiology and potential treatments of dysautonomias. The recently promulgated concept of the EAS updates Langley’s ANS to include neuroendocrine, immune/inflammatory, and central components. The homeostat theory builds on Cannon’s theory of homeostasis by proposing the existence of comparators (e.g., a thermostat, glucostat, carbistat, barostat) that receive information about regulated variables (e.g., core temperature, blood glucose, blood gases, delivery of blood to the brain). Homeostats sense discrepancies between the information and response algorithms. The presentation links the EAS with the homeostat theory to understand pathophysiological mechanisms of dysautonomias. Feed-forward anticipatory processes shift input–output curves and maintain plateau levels of regulated variables within different bounds of values—“allostasis”. Sustained allostatic processes increase long-term wear-and-tear on effectors and organs—allostatic load. They decreaseing thresholds for destabilizing and potentially fatal positive feedback loops. The homeostat theory enables mathematical models that define stress, allostasis, and allostatic load. The present discussion applies the EAS and homeostat concepts to specific examples of pediatric, adolescent/adult, and geriatric dysautonomias—familial dysautonomia, chronic orthostatic intolerance, and Lewy body diseases. Computer modeling has the potential to take into account the complexity and dynamics of allostatic processes and may yield testable predictions about individualized treatments and outcomes. Full article

Background: Mesotherapy is a procedure or a process of injecting drugs into the skin. This technique can help decrease the total drug dose due to its drug-sparing effect on the systemic route and can be utilized to treat nonspecific neck pain that occurs in the lateral and posterior neck. Methods: Ten patients with bilateral cervicobrachial pain were recruited and evaluated at T0 before treatments, T1 at the end of the treatment (42 days after T0), and T2 (72 days after T0). Assessments consisted of performing the Visual Analogue Scale (VAS) to evaluate pain evolution; a range of movement (ROM) and Bilateral trapezius’ tone, elasticity, and dynamic stiffness mensuration were performed using MyotonPro^®. All patients underwent mesotherapy treatment in the trapezius muscles with 1 cc of Diclofenac Sodium and 1 cc of lidocaine diluted in 3 cc of saline for a total of 6 weeks. Results: VAS value statistically decreased at T1 and T2; ROM of neck flexion statistically increased at T1 and T2, and miometric tone and stiffness value statistically improved at T1 and T2. Conclusion: mesotherapy with Diclofenac Sodium reduced pain intensity and improved functional outcomes, with no significant adverse effects in patients with myofascial pain syndrome of cervicobrachial localization. Full article

Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann–Whitney U test was used to assess statistical significance differences between groups. Results: No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p = 0.0151 and p = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant (p > 0.05). Neoangiogenesis (p = 0.0073) and anastomotic area epithelialization (p = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Discussion: The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses. Full article

Accurate minimally invasive anatomic liver (sub)segmentectomy (MIAS) is technically demanding and not yet standardized, and its surgical outcomes are undefined. To study the impact of the minimally invasive approach on perioperative outcomes of anatomic liver (sub)segmentectomy (AS), we retrospectively studied and compared perioperative outcomes of 99 open AS (OAS) and 112 MIAS (laparoscopic 77, robotic 35) cases using the extrahepatic Glissonean approach, based on the 1:1 propensity score matched analyses. After matching (71:71), MIAS was superior to OAS in terms of blood loss (p < 0.0001), maximum postoperative serum total bilirubin (p < 0.0001), C-reactive protein (p = 0.034) levels, R0 resection rate (p = 0.021), bile leak (p = 0.049), and length of hospital stay (p < 0.0001). The matched robotic and laparoscopic AS groups (30:30) had comparable outcomes in terms of operative time, blood loss, transfusion, open conversion, postoperative morbidity and mortality, R0 resection, and hospital stay, although the rate of Pringle maneuver application (p = 0.0002) and the postoperative aspartate aminotransferase level (p = 0.002) were higher in the robotic group. Comparing the matched posterosuperior (sub)segmentectomy cases or unmatched repeat hepatectomy cases between MIAS and OAS, we observed significantly less blood loss and shorter hospital stays in MIAS. Robotic AS yielded comparable outcomes with laparoscopic AS in the posterosuperior (sub)segmentectomy and repeat hepatectomy settings, despite the worse tumor and procedural backgrounds in robotic AS. In conclusion, various types of MIAS standardized by the extrahepatic Glissonean approach were feasible and safe with more favorable perioperative outcomes than those of OAS. Although robotic AS had almost comparable outcomes with laparoscopic AS, robotics may serve to decrease the surgical difficulty of MIAS in selected patients undergoing posterosuperior (sub)segmentectomy and repeat hepatectomy. Full article

(1) Background: Although vitamin D has many known biological effects, very little research has been conducted on how vitamin D may be related or play a role in endometriosis. The aim of our study was to perform an evaluation regarding vitamin D levels and possible implications in endometriosis through a statistical analysis of the data collected from the included studies. (2) Methods: For this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PubMed/Internet portal of the National Library of Medicine databases using several keywords related to our topic. (3) Results: Only nine articles were identified as complete or possessing the capacity to compute all available data. We totalized a number of 976 patients with endometriosis and 674 controls. From the nine studies included in our analysis, three of them claim there is no difference between women with and without endometriosis concerning 25(OH) vitamin D levels; however, the other six studies found significant differences regarding this aspect. (4) Conclusions: Our results underscored the complexity of analyzing the role of the vitamin D complex in a challenging condition like endometriosis and suggest that focusing on the tissue level might be essential to obtain accurate answers to our inquiries. Full article

The relationship between sleep and epilepsy is bidirectional. Certain epilepsy syndromes predominantly or exclusively manifest during sleep, with seizures frequently originating from non-rapid eye movement (NREM) sleep. Interictal epileptiform discharges observed on electroencephalograms are most likely to be activated during the deep NREM sleep stage known as N3. Conversely, epileptiform discharges, anti-seizure medications (ASMs), as well as other anti-seizure therapies can exert detrimental effects on sleep architecture. Moreover, the co-occurrence of sleep disorders has the potential to exacerbate seizure control. Understating the relationship between sleep and epilepsy is crucial for healthcare providers. Addressing and managing sleep-related problems in individuals with epilepsy can potentially contribute to improved seizure control and overall well-being. At the same time, improving seizure control can improve sleep quality and quantity, thus further improving the health of individuals with epilepsy. Full article

Lung cancer is the leading cause of cancer-related deaths among both men and women. African Americans (AAs) experience disproportionately higher incidence and mortality compared to other ethnic groups. Cytokines play multifaceted and crucial roles in the initiation, progression, and spread of cancer. Our aim was to identify cytokine biomarkers for the early detection of lung cancer in AAs. We examined eight key cytokines (Interleukin-1, IL-6, IL-8, IL-10, IL-12p70, monocyte chemotactic protein-1 (MCP-1), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)) in the plasma of 104 lung cancer patients and 48 cancer-free individuals using the FirePlex Immunoassay. These findings were subsequently validated in a separate cohort of 58 cases and 58 controls. IL-8, IFN-γ, and TNF-α exhibited elevated levels in both AA and White American (WA) lung cancer cases. Notably, IL-10 and MCP-1 displayed significant increases specifically in AA lung cancer patients, with MCP-1 levels associated with lung adenocarcinoma cases. Conversely, WA lung cancer patients showed heightened IL-6 levels, particularly linked to lung adenocarcinoma. The combined use of specific cytokines showed promise in lung cancer diagnosis, with IL-8, IL-10, and MCP-1 achieving 76% sensitivity and 79% specificity in AAs and IL-6 and IL-8 combined offering 76% sensitivity and 74% specificity in WAs. These diagnostic biomarkers were validated in the independent cohort. The ethnicity-related cytokine biomarkers hold promise for diagnosing lung cancer in AAs and WAs, potentially addressing the observed racial disparity. Full article

Internally rotated and adducted shoulder is a common posture in upper limb spasticity. Selective peripheral neurectomy is a useful and viable surgical technique to ameliorate spasticity, and the lateral pectoral nerve (LPN) could be a potential good target to manage shoulder spasticity presenting with internal rotation. However, there are some limitations related to this procedure, such as potential anatomical variability and the necessity of intraoperative surgical exploration to identify the target nerve requiring wide surgical incisions. This could result in higher post-surgical discomfort for the patient. Therefore, the aim of our study was to describe a modification of the traditional selective peripheral neurectomy procedure of the LPN through the perioperative ultrasound-guided marking of the target nerve with methylene blue. The details of the localization and marking procedure are described, as well as the surgical technique of peripheral selective neurectomy and the potential advantages in terms of nerve localization, surgical precision and patients’ post-surgical discomfort. We suggest that the proposed modified procedure could be a valid technique to address some current limitations and move the surgical treatment of spasticity toward increasingly tailored management due to the ease of nerve identification, the possibility of handling potential anatomical variability and the resulting smaller surgical incisions. Full article

Population aging and multimorbidity challenge health system sustainability, but the role of assistance-related variables rather than individual pathophysiological factors in determining patient outcomes is unclear. To identify assistance-related determinants of sustainable hospital healthcare, all patients hospitalised in an Internal Medicine Unit (n = 1073) were enrolled in a prospective year-long observational study and split 2:1 into a training (n = 726) and a validation subset (n = 347). Demographics, comorbidities, provenance setting, estimates of complexity (cumulative illness rating scale, CIRS: total, comorbidity, CIRS-CI, and severity, CIRS-SI subscores) and intensity of care (nine equivalents of manpower score, NEMS) were analysed at individual and Unit levels along with variations in healthcare personnel as determinants of in-hospital mortality, length of stay and nosocomial infections. Advanced age, higher CIRS-SI, end-stage cancer, and the absence of immune-mediated diseases were correlated with higher mortality. Admission from nursing homes or intensive care units, dependency on activity of daily living, community- or hospital-acquired infections, oxygen support and the number of exits from the Unit along with patient/physician ratios were associated with prolonged hospitalisations. Upper gastrointestinal tract disorders, advanced age and higher CIRS-SI were associated with nosocomial infections. In addition to demographic variables and multimorbidity, physician number and assistance context affect hospitalisation outcomes and healthcare sustainability. Full article

Lack of equitable representation of global genetic diversity has hampered the implementation of genomic medicine in under-represented populations, including those on the African continent. Data from the multi-national Pre-emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE) study suggest that genotype guidance for prescriptions reduced the incidence of clinically relevant adverse drug reactions (ADRs) by 30%. In this study, hospital dispensary trends from a tertiary South African (SA) hospital (Steve Biko Academic Hospital; SBAH) were compared with the drugs monitored in the PREPARE study. Dispensary data on 29 drugs from the PREPARE study accounted for ~10% of total prescriptions and ~9% of the total expenditure at SBAH. VigiLyze data from the South African Health Products Regulatory Authority were interrogated for local ADRs related to these drugs; 27 were listed as being suspected, concomitant, or interacting in ADR reports. Furthermore, a comparison of pharmacogene allele frequencies between African and European populations was used to frame the potential impact of pre-emptive pharmacogenetic screening in SA. Enumerating the benefit of pre-emptive pharmacogenetic screening in SA will only be possible once we initiate its full application. However, regional genomic diversity, disease burden, and first-line treatment options could be harnessed to target stratified PGx today. Full article

In the context of advancing healthcare, the diagnosis and treatment of cognitive disorders, particularly Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD), pose significant challenges. This review explores Artificial Intelligence (AI) and Machine Learning (ML) in neuropsychological assessment for the early detection and personalized treatment of MCI and AD. The review includes 37 articles that demonstrate that AI could be an useful instrument for optimizing diagnostic procedures, predicting cognitive decline, and outperforming traditional tests. Three main categories of applications are identified: (1) combining neuropsychological assessment with clinical data, (2) optimizing existing test batteries using ML techniques, and (3) employing virtual reality and games to overcome the limitations of traditional tests. Despite advancements, the review highlights a gap in developing tools that simplify the clinician’s workflow and underscores the need for explainable AI in healthcare decision making. Future studies should bridge the gap between technical performance measures and practical clinical utility to yield accurate results and facilitate clinicians’ roles. The successful integration of AI/ML in predicting dementia onset could reduce global healthcare costs and benefit aging societies. Full article

Parkinson’s disease is the second most common neurodegenerative disease and is increasing in incidence. The combination of motor and non-motor symptoms makes this a devastating disease for people with Parkinson’s disease and their care givers. Parkinson’s disease is characterised by mitochondrial dysfunction and neuronal death in the substantia nigra, a reduction in dopamine, accumulation of α-synuclein aggregates and neuroinflammation. The microbiome–gut–brain axis is also important in Parkinson’s disease, involved in the spread of inflammation and aggregated α-synuclein. The mainstay of Parkinson’s disease treatment is dopamine replacement therapy, which can reduce some of the motor signs. There is a need for additional treatment options to supplement available medications. Photobiomodulation (PBM) is a form of light therapy that has been shown to have multiple clinical benefits due to its enhancement of the mitochondrial electron transport chain and the subsequent increase in mitochondrial membrane potential and ATP production. PBM also modulates cellular signalling and has been shown to reduce inflammation. Clinically, PBM has been used for decades to improve wound healing, treat pain, reduce swelling and heal deep tissues. Pre-clinical experiments have indicated that PBM has the potential to improve the clinical signs of Parkinson’s disease and to provide neuroprotection. This effect is seen whether the PBM is directed to the head of the animal or to other parts of the body (remotely). A small number of clinical trials has given weight to the possibility that using PBM can improve both motor and non-motor clinical signs and symptoms of Parkinson’s disease and may potentially slow its progression. Full article

We sought to better understand the utility and role of animal models of infection for Food and Drug Administration (FDA)-approved antibiotics for the indications of community-, hospital-acquired-, and ventilator-associated bacterial pneumonia (CABP, HABP, VABP), complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), and acute bacterial skin and structural infections (ABSSSIs). We reviewed relevant documents from new drug applications (NDA) of FDA-approved antibiotics from 2014–2019 for the above indications. Murine neutropenic thigh infection models supported the choice of a pharmacokinetic-pharmacodynamic (PKPD) target in 11/12 NDAs reviewed. PKPD targets associated with at least a 1-log bacterial decrease were commonly considered ideal (10/12 NDAs) to support breakpoints. Plasma PK, as opposed to organ specific PK, was generally considered most reliable for PKPD correlation. Breakpoint determination was multi-disciplinary, accounting at minimum for epidemiologic cutoffs, non-clinical PKPD, clinical exposure-response and clinical efficacy. Non-clinical PKPD targets in combination with probability of target attainment (PTA) analyses generated breakpoints that were consistent with epidemiologic cutoffs and clinically derived breakpoints. In 6/12 NDAs, there was limited data to support clinically derived breakpoints, and hence the non-clinical PKPD targets in combination with PTA analyses played a heightened role in the final breakpoint determination. Sponsor and FDA breakpoint decisions were in general agreement. Disagreement may have arisen from differences in the definition of the optimal PKPD index or the ability to extrapolate protein binding from animals to humans. Overall, murine neutropenic thigh infection models supported the reviewed NDAs by providing evidence of pre-clinical efficacy and PKPD target determination, and played, in combination with PTA analysis, a significant role in breakpoint determination for labeling purposes. Full article

The cytogenomics-based methodology of directional genomic hybridization (dGH) enables the detection and quantification of a more comprehensive spectrum of genomic structural variants than any other approach currently available, and importantly, does so on a single-cell basis. Thus, dGH is well-suited for testing and/or validating new advancements in CRISPR-Cas9 gene editing systems. In addition to aberrations detected by traditional cytogenetic approaches, the strand specificity of dGH facilitates detection of otherwise cryptic intra-chromosomal rearrangements, specifically small inversions. As such, dGH represents a powerful, high-resolution approach for the quantitative monitoring of potentially detrimental genomic structural rearrangements resulting from exposure to agents that induce DNA double-strand breaks (DSBs), including restriction endonucleases and ionizing radiations. For intentional genome editing strategies, it is critical that any undesired effects of DSBs induced either by the editing system itself or by mis-repair with other endogenous DSBs are recognized and minimized. In this paper, we discuss the application of dGH for assessing gene editing-associated structural variants and the potential heterogeneity of such rearrangements among cells within an edited population, highlighting its relevance to personalized medicine strategies. Full article

Background: In recent years, increasingly complex ALI protocols involving specialized, albeit laboratory-specific media have been established, while at the same time, many studies compile the data of only a few ALI donors in spite of site-, protocol- and donor-specific differentiation. Methods: We describe a simple morphology scoring protocol using histology material derived from epithelia grown on ALI inserts in parallel to other, more complex readouts. Results: Among more than 100 ALI inserts derived from different donors, significant differences in layer score (p = 0.001) and goblet cell score (p = 0.002) were observed when ALI epithelia derived from explanted lung material were compared to trachea-derived ALI cultures. Cortisol withdrawal for the final 2 days of ALI cultures influenced goblet cell density (p = 0.001). Conclusions: While the histology score provides less resolution than FACS- or OMICs- based single cell analyses, the use of a subportion of the ALI epithelia grown on inserts makes it feasible to combine morphology assessment and other readouts of the same insert. This allows us to control for basic ALI morphology in research and personalized medicine settings in order to assess and, if desired, control for the impact of ALI culture protocols, site- and donor-specific influences on outcome of studies of ALI-derived epithelia. Full article

Colorectal cancer (CRC) is the third most prevalent and second most lethal cancer globally, with gene mutations and tumor metastasis contributing to its poor prognosis. Single-cell sequencing technology enables high-throughput analysis of the genome, transcriptome, and epigenetic landscapes at the single-cell level. It offers significant insights into analyzing the tumor immune microenvironment, detecting tumor heterogeneity, exploring metastasis mechanisms, and monitoring circulating tumor cells (CTCs). This article provides a brief overview of the technical procedure and data processing involved in single-cell sequencing. It also reviews the current applications of single-cell sequencing in CRC research, aiming to enhance the understanding of intratumoral heterogeneity, CRC development, CTCs, and novel drug targets. By exploring the diverse molecular and clinicopathological characteristics of tumor heterogeneity using single-cell sequencing, valuable insights can be gained into early diagnosis, therapy, and prognosis of CRC. Thus, this review serves as a valuable resource for identifying prognostic markers, discovering new therapeutic targets, and advancing personalized therapy in CRC. Full article

Accurate information regarding oxalate levels in foods is essential for managing patients with hyperoxaluria, oxalate nephropathy, or those susceptible to calcium oxalate stones. This study aimed to assess the reliability of chatbots in categorizing foods based on their oxalate content. We assessed the accuracy of ChatGPT-3.5, ChatGPT-4, Bard AI, and Bing Chat to classify dietary oxalate content per serving into low (<5 mg), moderate (5–8 mg), and high (>8 mg) oxalate content categories. A total of 539 food items were processed through each chatbot. The accuracy was compared between chatbots and stratified by dietary oxalate content categories. Bard AI had the highest accuracy of 84%, followed by Bing (60%), GPT-4 (52%), and GPT-3.5 (49%) (p < 0.001). There was a significant pairwise difference between chatbots, except between GPT-4 and GPT-3.5 (p = 0.30). The accuracy of all the chatbots decreased with a higher degree of dietary oxalate content categories but Bard remained having the highest accuracy, regardless of dietary oxalate content categories. There was considerable variation in the accuracy of AI chatbots for classifying dietary oxalate content. Bard AI consistently showed the highest accuracy, followed by Bing Chat, GPT-4, and GPT-3.5. These results underline the potential of AI in dietary management for at-risk patient groups and the need for enhancements in chatbot algorithms for clinical accuracy. Full article

The main recent change observed in the field of critical patient infection has been universal awareness of the need to make better use of antimicrobials, especially for the most serious cases, beyond the application of simple and effective formulas or rigid protocols. The increase in resistant microorganisms, the quantitative increase in major surgeries and interventional procedures in the highest risk patients, and the appearance of a significant number of new antibiotics in recent years (some very specifically directed against certain mechanisms of resistance and others with a broader spectrum of applications) have led us to shift our questions from “what to deal with” to “how to treat”. There has been controversy about how best to approach antibiotic treatment of complex cases of sepsis. The individualized and adjusted dosage, the moment of its administration, the objective, and the selection of the regimen are pointed out as factors of special relevance in a critically ill patient where the frequency of resistant microorganisms, especially among the Enterobacterales group, and the emergence of multiple and diverse antibiotic treatment alternatives have made the appropriate choice of antibiotic treatment more complex, requiring a constant updating of knowledge and the creation of multidisciplinary teams to confront new infections that are difficult to treat. In this article, we have reviewed the phenomenon of the emergence of resistance to antibacterials and we have tried to share some of the ideas, such as stewardship, sparing carbapenems, and organizational, microbiological, pharmacological, and knowledge tools, that we have considered most useful and effective for individualized decision making that takes into account the current context of multidrug resistance. The greatest challenge, therefore, of decision making in this context lies in determining an effective, optimal, and balanced empirical antibiotic treatment. Full article

The study’s aim was to examine alcohol consumption patterns and predictors of consumption across time among Hispanics with traumatic brain injury (TBI) in the U.S. within ten years post-injury. This longitudinal cohort study included 1342 Hispanic individuals (77.6% males) from the multi-site, longitudinal TBI Model Systems (TBIMS) database. The main outcome measures were consumption information, demographic, and injury characteristics. Across the full sample, alcohol consumption variables generally demonstrated quadratic movement characterized by an initial increase followed by a plateau or slight decrease over the ten years post-injury. The predictors of higher consumption were being men, single, with a history of excessive alcohol use, with a nonviolent mechanism of injury, shorter duration of PTA, and higher levels of education. Participants had a greater number of 5+ drinks/episode occurrences in the past month if they were men and had had a greater number of 5+ drinks/episode occurrences in the month before injury. There was no differential change in alcohol consumption over time as a function of these predictors. This study identified a profile of at-risk Hispanics with TBI for increased alcohol consumption. These individuals should be identified and targeted for early evidence-based alcohol intervention after TBI when results might be most favorable. Full article

The aim of our study was to evaluate the potential role of Artificial Intelligence tools like ChatGPT in patient education. To do this, we assessed both the quality and readability of information provided by ChatGPT 3.5 and 4 in relation to Anterior Cruciate Ligament (ACL) injury and treatment. ChatGPT 3.5 and 4 were used to answer common patient queries relating to ACL injuries and treatment. The quality of the information was assessed using the DISCERN criteria. Readability was assessed with the use of seven readability formulae: the Flesch–Kincaid Reading Grade Level, the Flesch Reading Ease Score, the Raygor Estimate, the SMOG, the Fry, the FORCAST, and the Gunning Fog. The mean reading grade level (RGL) was compared with the recommended 8th-grade reading level, the mean RGL among adults in America. The perceived quality and mean RGL of answers given by both ChatGPT 3.5 and 4 was also compared. Both ChatGPT 3.5 and 4 yielded DISCERN scores suggesting “good” quality of information, with ChatGPT 4 slightly outperforming 3.5. However, readability levels for both versions significantly exceeded the average 8th-grade reading level for American patients. ChatGPT 3.5 had a mean RGL of 18.08, while the mean RGL of ChatGPT 4 was 17.9, exceeding the average American reading grade level by 10.08 grade levels and 9.09 grade levels, respectively. While ChatGPT can provide both reliable and good quality information on ACL injuries and treatment options, the readability of the content may limit its utility. Additionally, the consistent lack of source citation represents a significant area of concern for patients and clinicians alike. If AI is to play a role in patient education, it must reliably produce information which is accurate, easily comprehensible, and clearly sourced. Full article

Cutaneous squamous cell carcinoma (cSCC) arising from the malignant proliferation of epidermal keratinocytes is the second most common skin cancer. Actinic keratosis (AK), which is considered cSCC in situ, may progress into invasive tumors. Currently, there are no serum markers that can differentiate cSCC from AK. The aim of our study was to assess angiogenesis and oxidative stress in patients with cSCC and patients with AK and find reliable serum markers useful in the diagnosis of cSCC. We have determined the serum levels of a group of proangiogenic factors (MMP-2, MMP-9, VEGF, FGF2), the total antioxidative status/capacity (TAS/TAC), ImAnOx, a marker of oxidative stress, and HIF-1 alpha, an indicator of hypoxia. We have identified higher serum levels of MMP-2. MMP-9, VEGF, FGF2 and HIF-1 alpha and lower levels of ImAnOx in cSCC patients compared to AK patients and controls. There were no statistically significant differences between AK patients and controls. We have found positive correlations between proangiogenic markers and HIF-1 alpha and negative correlations between proangiogenic markers and ImAnOx. Our results suggest that MMP-2, MMP-9, VEGF, FGF2, ImAnOx and HIF-1 may be promising markers for differentiating AK from cSCC, and there is a link between angiogenesis, oxidative stress and hypoxia. Full article

Background: Various predictive models have been published to identify outpatients with inadequate colonic cleansing who may benefit from intensified preparations to improve colonoscopy quality. The main objective of this study was to compare the accuracy of three predictive models for identifying poor bowel preparation in outpatients undergoing colonoscopy. Methods: This cross-sectional study included patients scheduled for outpatient colonoscopy over a 3-month period. We evaluated and compared three predictive models (Models 1–3). The quality of colonic cleansing was assessed using the Boston Bowel Preparation Scale. We calculated the area under the curve (AUC) and the corresponding 95% confidence interval for each model. Additionally, we performed simple and multiple logistic regression analyses to identify variables associated with inadequate colonic cleansing and developed a new model. Results: A total of 649 consecutive patients were included in the study, of whom 84.3% had adequate colonic cleansing quality. The AUCs of Model 1 (AUC = 0.67, 95% CI [0.63–0.70]) and Model 2 (AUC = 0.62, 95% CI [0.58–0.66]) were significantly higher than that of Model 3 (AUC = 0.54, 95% CI [0.50–0.58]; p < 0.001). Moreover, Model 1 outperformed Model 2 (p = 0.013). However, the new model did not demonstrate improved accuracy compared to the older models (AUC = 0.671). Conclusions: Among the three compared models, Model 1 showed the highest accuracy for predicting poor bowel preparation in outpatients undergoing colonoscopy and could be useful in clinical practice to decrease the percentage of inadequately prepared patients. Full article

Depression is the disorder with the greatest socioeconomic burdens. Its diagnosis is still based on an operational diagnosis derived from symptoms, and no objective diagnostic indicators exist. Thus, the present study aimed to develop an artificial intelligence (AI) model to aid in the diagnosis of depression from electroencephalography (EEG) data by applying machine learning to resting-state EEG and transcranial magnetic stimulation (TMS)-evoked EEG acquired from patients with depression and healthy controls. Resting-state EEG and single-pulse TMS-EEG were acquired from 60 patients and 60 healthy controls. Power spectrum analysis, phase synchronization analysis, and phase-amplitude coupling analysis were conducted on EEG data to extract feature candidates to apply different types of machine learning algorithms. Furthermore, to address the limitation of the sample size, dimensionality reduction was performed in a manner to increase the quality of information by featuring robust neurophysiological metrics that showed significant differences between the two groups. Then, nine different machine learning models were applied to the data. For the EEG data, we created models combining four modalities, including (1) resting-state EEG, (2) pre-stimulus TMS-EEG, (3) post-stimulus TMS-EEG, and (4) differences between pre- and post-stimulus TMS-EEG, and evaluated their performance. We found that the best estimation performance (a mean area under the curve of 0.922) was obtained using receiver operating characteristic curve analysis when linear discriminant analysis (LDA) was applied to the combination of the four feature sets. This study showed that by using TMS-EEG neurophysiological indices as features, it is possible to develop a depression decision-support AI algorithm that exhibits high discrimination accuracy. Full article

Background: Previous studies indicated common thyroid dysfunction in various kidney diseases. This study aimed to investigate the thyroid function in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with renal injury. Methods: Briefly, 174 patients diagnosed as having AAV with renal injury and without previous thyroid disease history were included in the retrospective and prospective study. The clinical parameters were collected and compared between different groups. Results: Of the patients included, 24 exhibited normal thyroid function, while 150 had thyroid dysfunction, including 55 (36.67%) with hypothyroidism. Those AAV patients with thyroid dysfunction showed different clinical parameters from those with normal thyroid function. The patients were followed up for a median of 68.6 (64.3; 72.8) months. Those with thyroid dysfunction were more prone to progressing to dialysis dependence compared to the group with normal thyroid function. Logistic regression analysis showed advanced age and decreased albumin as independent risk factors for thyroid dysfunction in patients with AAV. Survival analysis and multivariate Cox regression analysis showed that thyroid dysfunction was a risk factor for AAV patients with renal injury to progress to the endpoint of dialysis dependence. Conclusion: Thyroid dysfunction, predominantly hypothyroidism, was commonly complicated in AAV patients with renal injury. AAV patients with thyroid dysfunction were presented with different clinical parameters and more prone to progressing to dialysis dependence compared to those with normal thyroid function. Full article

PM2.5 is one of the most harmful components of airborne pollution and includes particles with diameters of less than 2.5 μm. Almost 90% of the world’s population lives in areas with poor air quality exceeding the norms established by the WHO. PM2.5 exposure affects various organs and systems of the human body including the upper respiratory tract which is one of the most prone to its adverse effects. PM2.5 can disrupt nasal epithelial cell metabolism, decrease the integrity of the epithelial barrier, affect mucociliary clearance, and alter the inflammatory process in the nasal mucosa. Those effects may increase the chance of developing upper respiratory tract diseases in areas with high PM2.5 pollution. PM2.5’s contribution to allergic rhinitis (AR) and rhinosinusitis was recently thoroughly investigated. Numerous studies demonstrated various mechanisms that occur when subjects with AR or rhinosinusitis are exposed to PM2.5. Various immunological changes and alterations in the nasal and sinonasal epithelia were reported. These changes may contribute to the observations that exposure to higher PM2.5 concentrations may increase AR and rhinosinusitis symptoms in patients and the number of clinical visits. Thus, studying novel strategies against PM2.5 has recently become the focus of researchers’ attention. In this review, we summarize the current knowledge on the effects of PM2.5 on healthy upper respiratory tract mucosa and PM2.5’s contribution to AR and rhinosinusitis. Finally, we summarize the current advances in developing strategies against PM2.5 particles’ effects on the upper respiratory tract. Full article

Long COVID is a recently described entity that is responsible for significant morbidity and that has consequences ranging from mild to life-threatening. The underlying mechanisms are not completely understood, and treatment options are currently limited, as existing data focus more on risk factors and predictors. Smoking has been reported as a risk factor for poor outcomes of acute SARS-CoV-2 infection and seems to also play a role in mediating post-COVID-19 symptoms. We aimed to review relevant work addressing the interaction between smoking and long COVID in order to characterize smoking’s role as a risk factor and possibly identify new research directions. Methods: The PubMed/MEDLINE database was searched using the keywords ‘smoking’, ‘long COVID’, and ‘post-acute COVID’ to identify relevant English-language articles published up to October 2023. Results and conclusions: From the 374 initial hits, a total of 36 papers were deemed relevant to the aim of the review. There was significant variability concerning the ways in which tobacco usage was quantified and reported; still, there is compelling evidence linking smoking to an increased risk of developing manifestations of post-acute-COVID disease. Some clinical conditions, such as dyspnea, cardiovascular symptoms, and cognitive or mental-health impairment, seem to be relatively strongly associated with smoking, while the connection between smoking and upper-airway involvement seems less certain. The available data support recommending smoking cessation as a clinical tool for the prevention of long COVID. Full article

Background: The treatment of choice for tumors located in the parotid gland is surgery. Nevertheless, postoperative complications are not infrequent. Regardless of the type of surgical procedure, the most common complication is Frey’s syndrome (FS). Traditionally, FS includes unilateral gustatory sweating and flushing of the facial skin lining the parotid compartment. Recent research describes atypical discomfort associated with FS. The aim of this study was to assess the late prevalence and severity of both usual and atypical symptoms after parotidectomy for benign tumors. Methods: We conducted a cross-sectional study involving 86 subjects who underwent superficial parotidectomy at least one year before the study. The questionnaire included the sweating–flushing–itch–paresthesia–pain (SFIPP) Frey scale supplemented by specific questions about symptoms. Results: Sixty-seven out of eighty-six (77.9%) cases reported almost one symptom. The most frequent symptom was itch (36/67—53.7%), followed by pain (35/67—52.2%), while 28/67 (41.8%) subjects complained of atypical symptoms without flushing or sweating. A desire to treat the discomfort was reported by 50/67 (74.6%) subjects. Conclusions: Late postparotidectomy local discomfort is not infrequent and includes both usual and “unusual” symptoms almost equally. Our results suggest the importance of informing patients about the occurrence of the syndrome and the available treatment options during pre- and postoperative counseling. Full article