J. Pers. Med., Volume 14, Issue 5 (May 2024) – 51 articles

This study aimed to investigate whether baroreflex sensitivity (BRS) could serve as a reliable metric for assessing cardiovascular autonomic neuropathy (CAN) and concurrently act as a surrogate biomarker for evaluating the severity of arterial stiffness and CAN in individuals diagnosed with type 2 diabetes mellitus (T2DM). Participants underwent brachial–ankle pulse wave velocity (baPWV) as well as autonomic function evaluations encompassing the Sudoscan-based modified composite autonomic scoring scale (CASS), baroreflex sensitivity, and heart rate variability in time domains and frequency domains. Linear regression analysis was performed to evaluate the influence of independent variables on baPWV and modified CASS. Participants with higher baPWV values were older, with longer diabetes duration, lower body weight, body mass index, waist circumference, elevated systolic and diastolic blood pressure, and mean arterial blood pressure. They also exhibited a higher prevalence of retinopathy as the underlying disease and reduced estimated glomerular filtration rate. Multiple linear regression analysis revealed that age and BRS were significantly associated with baPWV while diabetes duration, UACR, and BRS were significantly associated with modified CASS. Our study confirms the significant association of BRS with baPWV and modified CASS in T2DM, highlighting its pivotal role in linking microvascular and macrovascular complications. This supports BRS as a surrogate marker for assessing both the severity of arterial stiffness and cardiovascular autonomic neuropathy in T2DM, enabling the early identification of complications. Full article

Two-stage revision with an antibiotic-loaded cement articulating spacer is a standard treatment for chronic prosthetic knee infection (PKI); however, mechanical complications can occur during the spacer period. There is limited evidence on the association between surgeon volume and mechanical complications after resection arthroplasty (RA) using an articulating spacer. This study aimed to compare the rates of mechanical complications and reoperation after RA with articulating spacers by surgeons with high volumes (HV) and low volumes (LV) of RA performed and analyzed the risk factors for mechanical failure. The retrospective study investigated 203 patients treated with PKIs who underwent RA with articulating spacers and were divided according to the number of RAs performed by the surgeons: HV (≥14 RAs/year) or LV (<14 RAs/year). Rates of mechanical complications and reoperations were compared. Risk factors for mechanical complications were analyzed. Of the 203 patients, 105 and 98 were treated by two HV and six LV surgeons, respectively. The mechanical complication rate was lower in HV surgeons (3.8%) than in LV surgeons (36.7%) (p < 0.001). The reoperation rate for mechanical complications was lower in HV surgeons (0.9%) than in LV surgeons (24.5%) (p < 0.001). Additionally, 47.2% of patients required hinge knees after mechanical spacer failure. Medial proximal tibial angle < 87°, recurvatum angle > 5°, and the use of a tibial spacer without a cement stem extension were risk factors for mechanical complications. Based on these findings, we made the following three conclusions: (1) HV surgeons had a lower rate of mechanical complications and reoperation than LV surgeons; (2) mechanical complications increased the level of constraint in final revision knee arthroplasty; and (3) all surgeons should avoid tibial spacer varus malalignment and recurvatum deformity and always use a cement stem extension with a tibial spacer. Full article

Exercise promotes health and wellness, including its operation as a protective factor against a variety of psychological, neurological, and chronic diseases. Selenium and its biomarker, selenoprotein P (SEPP1), have been implicated in health, including cancer prevention, neurological function, and dopamine signaling. SEPP1 blood serum levels were compared with a one-way ANOVA between sedentary (SED), moderately exercised (MOD) [10 m/min starting at 10 min, increasing to 60 min], and high-intensity interval training (HIIT) exercised rats [30 min in intervals of 2-min followed by a 1-min break, speed progressively increased from 10 to 21 m/min]. HIIT rats showed significantly higher serum SEPP1 concentrations compared to MOD and SED. More specifically, HIIT exercise showed an 84% increase in SEPP1 levels compared to sedentary controls. MOD rats had greater serum SEPP1 concentrations compared to SED, a 33% increase. The results indicated that increased exercise intensity increases SEPP1 levels. Exercise-induced increases in SEPP1 may indicate an adaptive response to the heightened oxidative stress. Previous studies found a significant increase in dopamine D2 receptor (D2R) binding in these same rats, suggesting a potential association between SEPP1 and dopamine signaling during exercise. Modulating antioxidants like SEPP1 through personalized therapies, including exercise, has broad implications for health, disease, and addiction. Full article

Interleukin-8 (IL-8/CXCL8), an essential CXC chemokine, significantly influences psychoneuroimmunological processes and affects neurological and psychiatric health. It exerts a profound effect on immune cell activation and brain function, suggesting potential roles in both neuroprotection and neuroinflammation. IL-8 production is stimulated by several factors, including reactive oxygen species (ROS) known to promote inflammation and disease progression. Additionally, CXCL8 gene polymorphisms can alter IL-8 production, leading to potential differences in disease susceptibility, progression, and severity across populations. IL-8 levels vary among neuropsychiatric conditions, demonstrating sensitivity to psychosocial stressors and disease severity. IL-8 can be detected in blood circulation, cerebrospinal fluid (CSF), and urine, making it a promising candidate for a broad-spectrum biomarker. This review highlights the need for further research on the diverse effects of IL-8 and the associated implications for personalized medicine. A thorough understanding of its complex role could lead to the development of more effective and personalized treatment strategies for neuropsychiatric conditions. Full article

Metabolically healthy obesity (MHO) refers to obese individuals with a favorable metabolic profile, without severe metabolic abnormalities. This study aimed to investigate the potential of follistatin, a regulator of metabolic balance, as a biomarker to distinguish between metabolically healthy and unhealthy obesity. This cross-sectional study included 30 metabolically healthy and 32 metabolically unhealthy individuals with obesity. Blood samples were collected to measure the follistatin levels using an enzyme-linked immunosorbent assay (ELISA). While follistatin did not significantly differentiate between metabolically healthy (median 41.84 [IQR, 37.68 to 80.09]) and unhealthy (median 42.44 [IQR, 39.54 to 82.55]) individuals with obesity (p = 0.642), other biochemical markers, such as HDL cholesterol, triglycerides, C-peptide, and AST, showed significant differences between the two groups. Insulin was the most significant predictor of follistatin levels, with a coefficient of 0.903, followed by C-peptide, which exerted a negative influence at −0.624. Quantile regression analysis revealed nuanced associations between the follistatin levels and metabolic parameters in different quantiles. Although follistatin may not serve as a biomarker for identifying MHO and metabolically unhealthy obesity, understanding the underlying mechanisms that contribute to metabolic dysfunction could provide personalized strategies for managing obesity and preventing associated complications. Full article

This study aimed to categorize contrast media images associated with epidural, subdural, and combined epidural–subdural anesthesia in patients who had undergone fluoroscopy-guided epidural anesthesia using contrast media combined with monitored anesthesia care (MAC) targeted at deep sedation, incorporating capnography over 5 years. Additionally, a correlation was established between the anesthetic effects and radiographic findings according to the categorized imaging appearances. This study included 628 patients who underwent endoscopic, open, or fusion surgery under epidural anesthesia at Nanoori Hospital in Gangnam between March 2018 and September 2023. Fluoroscopy-guided epidural anesthesia using contrast media combined with MAC and capnography was used. The dataset included detailed radiographic imaging, nursing, and anesthesia records. Distinct patterns of anesthesia administration were observed, with 49%, 19.6%, and 31% of patients receiving epidural, subdural, and combined epidural–subdural anesthesia, respectively. The incidence and duration of motor block were significantly different among the three groups. Additionally, subdural anesthesia displayed a higher incidence of motor block and a prolonged motor deficit duration than epidural anesthesia. Fluoroscopic guidance using a contrast medium for epidural and subdural anesthesia ensures precise space identification and prevents serious anesthetic complications. Our findings suggest the potential to achieve stable anesthesia, particularly using subdural and combined epidural–subdural anesthesia. Full article

Severe cancer pain substantially affects patients’ quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD). Oxycodone/naloxone combination therapy has emerged as a promising approach to mitigate opioid-induced constipation (OIC) while providing effective pain relief. This review provides an updated analysis of the literature of the last decade regarding the use of oxycodone/naloxone in the management of severe cancer pain. Through a comprehensive search of databases, studies focusing on the efficacy, safety, and patient experience of oxycodone/naloxone’s prolonged release in severe cancer pain management were identified. Furthermore, the literature discusses the mechanism of action of naloxone in mitigating OIC without compromising opioid analgesia. Overall, the evidence suggests that oxycodone/naloxone combination therapy offers a valuable option for effectively managing severe cancer pain while minimizing opioid-induced constipation, thereby improving patients’ quality of life. However, further research is needed to optimize dosing regimens, evaluate long-term safety, and assess patient outcomes in diverse cancer populations. Full article

Background: Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs. Objective: To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS. Materials and Methods: We measured autoantibodies against the gnAChR α3 and β4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD. Results: Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID. Conclusions: We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies. Full article

Radiotherapy is focused on the tumor but also reaches healthy tissues, causing toxicities that are possibly related to genomic factors. In this context, radiogenomics can help reduce the toxicity, increase the effectiveness of radiotherapy, and personalize treatment. It is important to consider the genomic profiles of populations not yet studied in radiogenomics, such as the indigenous Amazonian population. Thus, our objective was to analyze important genes for radiogenomics, such as ATM, TGFB1, RAD51, AREG, XRCC4, CDK1, MEG3, PRKCE, TANC1, and KDR, in indigenous people and draw a radiogenomic profile of this population. The NextSeq 500^® platform was used for sequencing reactions; for differences in the allelic frequency between populations, Fisher’s Exact Test was used. We identified 39 variants, 2 of which were high impact: 1 in KDR (rs41452948) and another in XRCC4 (rs1805377). We found four modifying variants not yet described in the literature in PRKCE. We did not find any variants in TANC1—an important gene for personalized medicine in radiotherapy—that were associated with toxicities in previous cohorts, configuring a protective factor for indigenous people. We identified four SNVs (rs664143, rs1801516, rs1870377, rs1800470) that were associated with toxicity in previous studies. Knowing the radiogenomic profile of indigenous people can help personalize their radiotherapy. Full article

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces “enhanced exosomes”, a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HtrA1, PAM, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified the altered expression of various miRNAs, such as miR-125b-5p and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women’s reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders. Full article

Background: KEYNOTE-522 resulted in FDA approval of the immune checkpoint inhibitor pembrolizumab in combination with neoadjuvant chemotherapy for patients with early-stage, high-risk, triple-negative breast cancer (TNBC). Unfortunately, pembrolizumab is associated with several immune-related adverse events (irAEs). We aimed to identify potential tumor microenvironment (TME) biomarkers which could predict patients who may attain pathological complete response (pCR) with chemotherapy alone and be spared the use of anti-PD-1 immunotherapy. Methods: Comprehensive immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on matched FFPE tumor samples from 22 stage I-III TNBC patients (14 patients treated with neoadjuvant chemotherapy alone (NAC) and 8 treated with neoadjuvant chemotherapy combined with pembrolizumab (NAC+I)). Results: Differential gene expression analysis revealed that in the NAC group, IL12B and IL13 were both significantly associated with pCR. In the NAC+I group, LCK and TP63 were significantly associated with pCR. Patients in both treatment groups exhibiting pCR tended to have greater tumor inflammation than non-pCR patients. In the NAC+I group, patients with pCR tended to have greater cell proliferation and higher PD-L1 expression, while in the NAC group, patients with pCR tended to have lower cancer testis antigen expression. Additionally, the NAC+I group trended toward a lower relative dose intensity averaged across all chemotherapy drugs, suggesting that more dose reductions or treatment delays occurred in the NAC+I group than the NAC group. Conclusions: A comprehensive understanding of immunologic factors could potentially predict pCR to chemotherapy alone, enabling the avoidance of the unnecessary treatment of these patients with checkpoint inhibitors. Full article

The fetal splenic artery pulsatility index is a parameter that reflects fetal well-being and has been used as a predictor of adverse pregnancy outcomes. The aim of this study was to investigate the predictive value of the splenic artery pulsatility index in gestational diabetes mellitus class A1 cases for intensive care unit admission. In this prospective case-controlled study, only sixty single pregnancy cases diagnosed with gestational diabetes mellitus class A1 were evaluated. Fetal splenic artery Doppler parameters such as peak systolic velocity, pulsatility index, resistivity index, and end-diastolic velocity were measured in all cases. The rate of requirements for the neonatal intensive care unit was noted. In cases requiring fetal intensive care, the fetal splenic pulsatility index was found to be statistically significantly lower than in healthy cases without it (0.94 ± 0.29 vs. 1.70 ± 0.53, respectively, p < 0.001, Student’s t-test). When the fetal splenic PI cutoff value was selected as 1.105 cm3, the sensitivity was calculated as 97.9% and the specificity as 58.3% for predicting the need for fetal intensive care (AUC 0.968, p < 0.001, 95% CI 0.929–0.998). The use of a low fetal splenic artery PI parameter is a significant and good indicator for predicting the need for fetal intensive care according to the binary logistic regression analysis result (p = 0.006). This study suggests that evaluation of fetal splenic artery Doppler in mothers with gestational diabetes mellitus may be used to predict neonates requiring a newborn intensive care unit. Therefore, it is recommended that obstetricians use this simple, rapid, and valuable evaluation of fetal splenic artery Doppler and alert the neonatologist that a newborn intensive care unit may be required. Full article

The purpose of this study was to conduct a cross-sectional analysis of the association between hearing aid use and cognitive decline in community-dwelling older adults with hearing impairment, stratified by cardiovascular risk level. This cross-sectional study covers 1857 hearing-impaired individuals selected among 10,674 community-dwelling older adults (≥65 years of age) in Japan. We investigate the association between hearing aid use and cognitive decline stratified by cardiovascular risk level, by assessing self-reported hearing impairment and hearing aid use, absolute cardiovascular risk, cognitive function, and potential confounding factors. The association between hearing impairment severity and increased cardiovascular risk, and the benefit of hearing aid use in preventing cognitive decline, were examined in a binomial logistic regression analysis, with the presence of cognitive decline as the objective variable. In the low cardiovascular risk group, hearing aid users had a lower odds ratio for decline in executive function than non-users (odds ratio = 0.61, 95% confidence interval: 0.39–0.98). However, there was no significant association between hearing aid use and cognitive decline in the high cardiovascular risk group (p > 0.05). Among older adults with hearing impairment, hearing aid use was associated with the maintenance of executive function in individuals of low cardiovascular risk. Full article

PD-L1 immunohistochemistry (IHC) has become an established method for predicting cancer response to targeted anti-PD1 immunotherapies, including breast cancer (BC). The alternative PD-1 ligand, PD-L2, remains understudied but may be a complementary predictive marker. Prospective analysis of 32 breast cancers revealed divergent expression patterns of PD-L1 and PD-L2. PD-L1-positivity was higher in immune cells than in cancer cells (median = 5.0% vs. 0.0%; p = 0.001), whereas PD-L2-positivity was higher in cancer cells than immune cells (median = 30% vs. 5.0%; p = 0.001). Percent positivity of PD-L1 and PD-L2 were not correlated, either in cancer cells or immune cells. Based on a cut-point of >1% positivity, ER+ tumors (n = 23) were frequently PD-L2-positive (73.9%), whereas only 40.9% were PD-L1-positive. These data suggest differential control of cellular PD-L1 and PD-L2 expression in BC and a potential role for PD-L2 IHC as a complementary marker to PD-L1 to improve selection of aggressive ER+ BC that may benefit from anti-PD-1 therapy. Full article

Background: Acute compartment syndrome is a major surgical emergency with complex pathophysiology and a highly unpredictable pattern of evolution. We hypothesized that the onset of acute compartment syndrome of the leg or forearm is associated with variations in the surface temperature of the distal segment (foot or hand) with a distinct pattern, which acts as an early warning sign. Materials and Methods: We developed a monitoring device that consists of two thermic sensors attached to a modular limb splint, which continuously measure the temperature difference between the proximal and distal regions of the limb (i.e., arm–hand, thigh–foot). Firstly, we investigated both the arm–hand and thigh–foot temperature gradients of hospitalized patients’ healthy limbs (43 patients, 56 upper limbs, 64 lower limbs) in order to establish a baseline. Secondly, we examined the correlation between the thermic gradients and intracompartmental pressure values in compartment syndrome limbs (20 patients, 6 upper limbs, 14 lower limbs). Results: For the control group, the mean values for the normal limb thermic gradients were −0.17 °C for the upper limbs. and 0.03 °C for the lower limbs. In the impending compartment syndrome group (defined by intracompartmental pressure values), the mean index was −0.38 °C. In the fully developed compartment syndrome group, the mean value was 4.11 °C. Discussions: Analysis was performed using the ANOVA one-way statistical method. This showed significant differences between the compartment syndrome group and the impending and control groups. A decreasing trend in the thermic gradient in patients with impending compartment syndrome compared with the control group was noted. Conclusions: The thermic gradient of limbs presenting signs of impending compartment syndrome decreases as a result of the increased temperature of the distal segment. This pattern can be used as an early diagnostic method for acute compartment syndrome. This technique is non-invasive and bears no risk to the patient, allowing facile continuous monitoring during immobilization. Full article

(1) Background: This study evaluates the predictive effectiveness of biomarkers in diagnosing newborn sepsis. (2) Methods: This was a case–control study conducted on neonates hospitalized at the Clinical Hospital “Louis Turcanu”, Timisoara, Romania, from October 2018 to July 2023. Using a vacutainer collection device, venous blood was collected at admission for complete blood tests, including ferritin, hemoglobin, LDH, and blood culture analysis. Neonates were divided into two groups: sepsis-positive and sepsis-negative. The outcome of interest was a diagnosis of sepsis. (3) Results: Data from 86 neonates, 51 of whom had been confirmed to have sepsis, were analyzed. This study found no significant difference in gestational age, infant weight, fetal growth restriction, or APGAR score between neonates with and without sepsis. However, there was a higher incidence of sepsis among neonates delivered via cesarean section. Neonatal patients with sepsis showed significantly higher levels of neonatal serum ferritin and LDH compared to those without sepsis. Ferritin and LDH biomarkers demonstrated excellent discriminatory capabilities in diagnosing neonatal sepsis. Logistic regression analysis revealed a significant association between elevated ferritin and LDH levels and the likelihood of neonatal sepsis, while anemia did not show a significant association. (4) Conclusions: LDH and ferritin concentrations are found to be predictive biomarkers for neonatal sepsis, indicating a potential role in detecting susceptible neonates and implementing prompt interventions to improve patient outcomes. Full article

The massive amount of human biological, imaging, and clinical data produced by multiple and diverse sources necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell-signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels, as well as their orchestration and links, are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof-of-concept study cases. Personalized simulations of the actual anatomy of a patient have been conducted. The hypermodel has also been applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin-based clinical decision support system and as the core of future in silico trial platforms, although additional retrospective adaptation and validation are necessary. Full article

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s′), can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognosis of PH. Full article

Background: Understanding the dynamics of conduction velocity (CV) and voltage amplitude (VA) is crucial in cardiac electrophysiology, particularly for substrate-based catheter ablations targeting slow conduction zones and low voltage areas. This study utilizes ultra-high-density mapping to investigate the impact of heart rate and pacing location on changes in the wavefront direction, CV, and VA of healthy pig hearts. Methods: We conducted in vivo electrophysiological studies on four healthy juvenile pigs, involving various pacing locations and heart rates. High-resolution electroanatomic mapping was performed during intrinsic normal sinus rhythm (NSR) and electrical pacing. The study encompassed detailed analyses at three levels: entire heart cavities, subregions, and localized 5-mm-diameter circular areas. Linear mixed-effects models were used to analyze the influence of heart rate and pacing location on CV and VA in different regions. Results: An increase in heart rate correlated with an increase in conduction velocity and a decrease in voltage amplitude. Pacing influenced conduction velocity and voltage amplitude. Pacing also influenced conduction velocity and voltage amplitude, with varying effects observed based on the pacing location within different heart cavities. Pacing from the right atrium (RA) decreased CV in all heart cavities. The overall CV and VA changes in the whole heart cavities were not uniformly reflected in all subregions and subregional CV and VA changes were not always reflected in the overall analysis. Overall, there was a notable variability in absolute CV and VA changes attributed to pacing. Conclusions: Heart rate and pacing location influence CV and VA within healthy juvenile pig hearts. Subregion analysis suggests that specific regions of the heart cavities are more susceptible to pacing. High-resolution mapping aids in detecting regional changes, emphasizing the substantial physiological variations in CV and VA. Full article

Background: Reducing a child’s level of anxiety before magnetic resonance imaging (MRI) procedures allows for better behavioral outcomes. The aim of this retrospective study was to evaluate anxiolytic efficacy of Midazolam/γ-cyclodextrin oral formulation. Methods: We retrospectively reviewed 100 medical charts of children who, between 1 February and 31 July 2022, underwent MRI under general anesthesia with or without premedication with midazolam/γ-cyclodextrin. Primary outcome was comparison of behavior to facemask positioning, while secondary endpoints were degree of drugs acceptance, anxiolytic effect evaluation, child’s behavior on separation, and sevoflurane need. Results: Facemask positioning was accepted by 58% of the midazolam/γ-cyclodextrin group compared to 22% of children in the control group. The rate of acceptance was >90%. At the moment of separation from parent, none of the premedicated children needed to be restrained compared to 18% in the control group. A lower percentage of sevoflurane was needed for eye-closure at induction of anesthesia and for anesthesia maintenance. At emergence from anesthesia, 46% of children in the premedicated group compared to 66% of children in the control group showed transient agitation. Conclusions: Midazolam/γ-cyclodextrin showed a good profile of acceptance, satisfactory anxiolytic properties, and reduced need for anesthetics when administered to children before MRI under general anesthesia. Full article

Aim: To investigate inflammation indices and erythropoietin levels for their potential role in distinguishing polycythemia vera from secondary polycythemia and to compare different parameter combinations in terms of the diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. Polycythemia vera diagnosis was made according to the 2016 World Health Organization criteria (n = 145). Those who did not fulfill the criteria were defined as having secondary polycythemia (n = 84). Results: The neutrophil lymphocyte ratio, platelet lymphocyte ratio and systemic immune-inflammation index were significantly higher in the polycythemia vera group (p < 0.001 for all). Erythropoietin had the highest area under the curve in the analysis to distinguish groups, followed by the systemic immune-inflammation index. The platelet lymphocyte ratio (≥135) had the highest specificity to detect polycythemia vera, followed closely by the systemic immune-inflammation index. The sensitivity for polycythemia vera detection was highest with the erythropoietin and systemic immune-inflammation index combination, followed by erythropoietin and the neutrophil lymphocyte ratio. All the single and combinatory variables exhibited significant performance in predicting polycythemia vera after adjusting for age and sex. However, the erythropoietin and systemic immune-inflammation index combination had the highest odds ratio, followed by erythropoietin alone. Conclusion: These are promising findings supporting the usability of these biomarkers, especially the systemic immune-inflammation index, as minor criteria in the diagnosis of polycythemia vera. It is especially crucial to note that using erythropoietin in combination with these markers may improve diagnostic accuracy. Full article

The primary goal of this study was to investigate the knowledge, prevalence, and risk factors of cardiovascular diseases among individuals in the Najran region of Saudi Arabia. In the Najran region of Saudi Arabia, an online cross-sectional survey was conducted. Between September and October 2023, a self-administered questionnaire was distributed to a random sample of the general population aged 18 and up. The survey instrument asked about history and exposure, physician-diagnosed illnesses, cardiovascular diseases (CVDs), medication use, and other risk factors. This research had a total of 2046 individuals. Around one-fifth of the study participants reported that they or a family member suffered from CVD, and arrhythmia was the most commonly reported; blood tests, cardiac catheterization, and ECG were the most commonly reported tests performed for CVD patients, around one-tenth of CVD patients reported that they do not have any chronic diseases other than CVD, and the vast majority of the patients confirmed their regular medical appointments. This is one of the first studies to investigate the knowledge, prevalence, and use of CVD drugs among individuals in the Najran region of Saudi Arabia. The study participants’ lack of knowledge about CVD could lead to ineffective preventive measures and poor patient outcomes. The study’s findings underscore the crucial need for more extensive and efficient educational initiatives that consider the targeted population’s talents, attitudes, and perceptions. Full article

A cesarean scar ectopic pregnancy (CSP) represents an uncommon yet potentially life-threatening condition requiring immediate and efficient management. We present a case of a 32-year-old woman diagnosed with a scar pregnancy at 8 weeks of gestation. Laparoscopic surgical management was chosen due to its minimally invasive nature and potential for preserving fertility. During the procedure, temporary clipping of uterine arteries was employed to control intraoperative bleeding. The patient recovered well postoperatively with no complications. This case highlights the feasibility and effectiveness of laparoscopic intervention combined with temporary uterine artery clipping in the management of scar pregnancies, offering a valuable approach for clinicians faced with similar cases. Through this report, we aim to contribute to the existing literature on the optimal management of CSP and highlight the efficacy of laparoscopic surgery in this context. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with Dupilumab in different rhinological units were considered for this study via their evaluation at the baseline at first and the consequential follow-up at 6-, 12-, and 24 months from the first administration. At baseline (T0) and at each follow-up, patients underwent NPS, Sinonasal Outcome Test (SNOT)-22, Visual Analogue Scale (VAS) for smell, and Sniffin’ sticks identification test (SSIT). The SNOT-22 domains for function and emotion were also analysed separately. Two hundred and seventeen patients with at least 6 months of follow-up were included. All parameters have improved during treatment (p < 0.0001). Noticeably, both the function and emotion SNOT-22 domains have improved within 6 months of treatment and have continued to progress during every interval within 12 months from the baseline, positively influencing patients’ emotivity and augmenting their social and economic performances. Dupilumab improves the QoL of CRSwNP patients with good effects on the reported productivity and emotional health. Clinicians should pay attention to these two aspects when dealing with patients affected by severe CRSwNP. Full article

The article discusses the importance of accurately distinguishing HER2-low from HER2-negative breast cancer, as novel ADCs have demonstrated activity in a large population of patients with HER2-low-expressing BC. While current guidelines recommend a dichotomous classification of HER2 as either positive or negative, the emergence of the HER2-low concept calls for standardization of HER2 testing in breast cancer, using currently available assays to better discriminate HER2 levels. This review covers the evolution and latest updates of the ASCO/CAP guidelines relevant to this important biomarker in breast cancer, including still-evolving concepts such as HER2 low, HER2 heterogeneity, and HER2 evolution. Our group presents the latest Mexican recommendations for HER2 status evaluation in breast cancer, considering the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, accurate HER2 status assessment remains one of the most important biomarkers in breast cancer, and the commitment of Mexican pathologists to theragnostic biomarker quality is crucial for providing the most efficient care in oncology. Full article

Endometriosis is a chronic gynecological disorder with a multifactorial etiology that has not yet been fully elucidated. What is known, however, are the pathological tissue dynamics that lead to the complex symptoms that women suffer from. The known symptoms are mainly fertility problems and pain. Both dimensions have an impact that varies from case to case, but that is certainly decisive concerning a woman’s health, specifically by affecting the overall quality of life (QoL). In this publication, we will deal with the descriptive aspects of endometriosis’s pathology and then present a review of the aspects impacting QoL and their psycho-social consequences. Finally, the experience of pain in the context of the mind–brain–body relationship will be discussed, describing the complexity of this dimension and emphasizing the importance of a multi-professional approach that considers the relevance of the contribution that a psychotherapy intervention based on up-to-date neurobiological models can make for women with endometriosis. A review of the literature and current knowledge on the neural and psychological aspects of pain lead to the conclusion that it is of the utmost importance to provide informed psychological support, alongside medical treatments and sexual counseling, to patients with endometriosis. Full article

Background: Spontaneous orbital cephaloceles are a rare condition. The purpose of this study is to provide a description of a clinical case and to carry out a systematic literature review. Methods: A systematic review of the English literature published on the Pubmed, Scopus, and Web of Science databases was conducted, according to the PRISMA recommendations. Results: A 6-year-old patient was admitted for right otomastoiditis and thrombosis of the sigmoid and transverse sinuses, as well as the proximal portion of the internal jugular vein. Radiological examinations revealed a left orbital mass (22 × 14 mm) compatible with asymptomatic orbital meningocele (MC) herniated from the superior orbital fissure (SOF). The child underwent a right mastoidectomy. After the development of symptoms and signs of intracranial hypertension (ICH), endovascular thrombectomy and transverse sinus stenting were performed, with improvement of the clinical conditions and reduction of the orbital MC. The systematic literature review encompassed 29 publications on 43 patients with spontaneous orbital MC. In the majority of cases, surgery was the preferred treatment. Conclusions: The present case report and systematic review highlight the importance of ICH investigation and a pathophysiological-oriented treatment approach. The experiences described in the literature are limited, making the collection of additional data paramount. Full article

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2−) early-stage breast cancer (esBC) is still to be confirmed. Methods: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. Results: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). Conclusions: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2− esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits. Full article

Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The aim of this review is to identify HER2 membrane overexpression in relation to pancreatic cancer pathways that can be used in order to develop a targeted therapy. After searching the keywords, 174 articles were found during a time span of 10 years, between 2013 and 2023, but only twelve scientific papers were qualified for this investigation. The new era of biomolecular research found a significant relationship between HER2 overexpression and pancreatic cancer cells in 25–30% of cases. The variables are dependent on tumor-derived cells, with differences in receptor overexpression between PDAC (pancreatic ductal adenocarcinoma), BTC (biliary tract cancer), ampullary carcinoma, and PNETs (pancreatic neuroendocrine tumors). HER2 overexpression is frequently encountered in human pancreatic carcinoma cell lines, and the ERBB family is one of the targets in the near future of therapy, with good results in phase I, II, and III studies evaluating downregulation and tumor downstaging, respectively. Full article

Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application. Full article