Bilateral Spigelian Hernias Robotic Repair: A Novel Approach to a Rare Surgical Entity.

Spigelian hernias are an uncommon protrusion defect noted between the rectus abdominis and the transversus abdominis muscles, at the semilunar line, with a low incidence of approximately 0.12% to 2% of all ventral hernias. Furthermore, the incidence of bilateral cases is noted to be even lower in the general population. They are associated with bowel incarceration and strangulation; hence surgical repair is indicated. Therapeutic alternatives for Spigelian hernias include open repair, however laparoscopic repair stands as the standard of care in these cases. Feasible and successful robotic repair has been reported, with associated advantages in terms of visualization and surgical instrument dexterity. We present the first ever reported cases of bilateral Spigelian hernias repaired using robotic approach. Two female Puerto Rican patients referred to our institution complaining of abdominal pain, where imaging studies found bilateral Spigelian hernias. In both cases, a transabdominal preperitoneal repair was performed using the Da Vinci Surgical System. Both patients were discharged home tolerating oral intake with adequate wound healing. On follow up visits, patients denied abdominal discomfort and had adequate wound healing. Robotic surgery for Spigelian hernias poses an advantage over laparoscopic repair as improved visualization, mobility, and precision in movements allow for more gentle tissue manipulation. Furthermore, this is the first evidence of safe and effective repair in the uncommon entity of bilateral cases, providing a newer alternative in the setting of such presentation.

Exploring the Integrated Role of miRNAs and lncRNAs in Regulating the Transcriptional Response to Amino Acids and Insulin-like Growth Factor 1 in Gilthead Sea Bream (Sparus aurata) Myoblasts.

In this study, gilthead sea bream (Sparus aurata) fast muscle myoblasts were stimulated with two pro-growth treatments, amino acids (AA) and insulin-like growth factor 1 (Igf-1), to analyze the transcriptional response of mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and to explore their possible regulatory network using bioinformatic approaches. AA had a higher impact on transcription (1795 mRNAs changed) compared to Igf-1 (385 mRNAs changed). Both treatments stimulated the transcription of mRNAs related to muscle differentiation (GO:0042692) and sarcomere (GO:0030017), while AA strongly stimulated DNA replication and cell division (GO:0007049). Both pro-growth treatments altered the transcription of over 100 miRNAs, including muscle-specific miRNAs (myomiRs), such as miR-133a/b, miR-206, miR-499, miR-1, and miR-27a. Among 111 detected lncRNAs (>1 FPKM), only 30 were significantly changed by AA and 11 by Igf-1. Eight lncRNAs exhibited strong negative correlations with several mRNAs, suggesting a possible regulation, while 30 lncRNAs showed strong correlations and interactions with several miRNAs, suggesting a role as sponges. This work is the first step in the identification of the ncRNAs network controlling muscle development and growth in gilthead sea bream, pointing out potential regulatory mechanisms in response to pro-growth signals.

Early automated cerebral edema assessment following endovascular therapy: impact on stroke outcome.

BACKGROUND: Cerebral edema (CED) is associated with poorer outcome in patients with acute ischemic stroke (AIS). The aim of the study was to investigate the factors contributing to greater early CED formation in patients with AIS who underwent endovascular therapy (EVT) and its association with functional outcome. METHODS: We conducted a multicenter cohort study of patients with an anterior circulation AIS undergoing EVT. The volume of cerebrospinal fluid (CSF) was extracted from baseline and 24-hour follow-up CT using an automated algorithm. The severity of CED was quantified by the percentage reduction in CSF volume between CT scans (∆CSF). The primary endpoint was a shift towards an unfavorable outcome, assessed by modified Rankin Scale (mRS) score at 3 months. Multivariable ordinal logistic regression analyses were performed. The ∆CSF threshold that predicted unfavorable outcome was selected using receiver operating characteristic curve analysis. RESULTS: We analyzed 201 patients (mean age 72.7 years, 47.8% women) in whom CED was assessable for 85.6%. Higher systolic blood pressure during EVT and failure to achieve modified Thrombolysis In Cerebral Infarction (mTICI) 3 were found to be independent predictors of greater CED. ∆CSF was independently associated with the probability of a one-point worsening in the mRS score (common odds ratio (cOR) 1.05, 95% CI 1.03 to 1.08) after adjusting for age, baseline mRS, National Institutes of Health Stroke Scale (NIHSS), and number of passes. Displacement of more than 25% of CSF was associated with an unfavorable outcome (OR 6.09, 95% CI 3.01 to 12.33) and mortality (OR 6.72, 95% CI 2.94 to 15.32). CONCLUSIONS: Early CED formation in patients undergoing EVT was affected by higher blood pressure and incomplete reperfusion. The extent of early CED, measured by automated ∆CSF, was associated with worse outcomes.

Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Vasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850 K CpG sites) in whole-blood samples collected at hospital admission. We identified differentially methylated positions (DMPs) at the CpG level using Cox regression models adjusted for potential confounders, and then we used the DMP results to find differentially methylated regions (DMRs) and enriched biological pathways. A total of 145 patients (51%) experienced vasospasm. In the DMP analysis, we identified 31 CpGs associated with vasospasm at p-value < 10-5. One of them (cg26189827) was significant at the genome-wide level (p-value < 10-8), being hypermethylated in patients with vasospasm and annotated to SUGCT gene, mainly expressed in arteries. Region analysis revealed 13 DMRs, some of them annotated to interesting genes such as POU5F1, HLA-DPA1, RUFY1, and CYP1A1. Functional enrichment analysis showed the involvement of biological processes related to immunity, inflammatory response, oxidative stress, endothelial nitric oxide, and apoptosis. Our findings show, for the first time, a distinctive epigenetic signature of vasospasm in aSAH, establishing novel links with essential biological pathways, including inflammation, immune responses, and oxidative stress. Although further validation is required, our results provide a foundation for future research into the complex pathophysiology of vasospasm.

Stroke-associated pneumonia according to mCDC criteria: impact on prognosis and antibiotic therapy.

Objective: The modified Centers for Disease Control and Prevention (mCDC) criteria have been proposed for diagnosing and managing stroke-associated pneumonia (SAP). The objective was to investigate the impact of SAP on stroke outcome depending on whether or not it conforms to mCDC criteria. Our secondary objective was to identify the responsible factors for antibiotic initiation in stroke patients. Methods: We conducted a prospective, multicenter, observational study of ischemic stroke patients with moderate to severe stroke (NIHSS≥4) admitted within 24 h. For 7 days, mCDC criteria were assessed daily, and infections and antibiotics were recorded. Pneumonias were divided into those fulfilling mCDC criteria (mCDC-SAP) or not (other pneumonias, OPn). The effect of each type of pneumonia on 3-month outcome was evaluated in separated logistic regression models. Factors associated with antibiotic initiation were explored using a random forest analysis. Results: Of the 342 patients studied, infections were diagnosed in 72 (21.6%), including 39 (11.7%) cases of pneumonia. Of them, 25 (7.5%) fulfilled mCDC criteria. Antibiotics were used in 92% of mCDC-SAP and 64.3% of OPn. In logistic regression analysis, mCDC-SAP, but not OPn, was an independent predictor of poor outcome [OR, 4.939 (1.022-23.868)]. The random forest analysis revealed that fever had the highest importance for antibiotic initiation. Interpretation: The mCDC criteria might be useful for detecting clinically relevant SAP, which is associated with poor outcomes. Isolated signs of infection were more important for antibiotic initiation than compliance with pre-defined criteria. Therefore, adherence to mCDC criteria might result in antibiotic saving without compromising clinical outcome.

The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review.

This comprehensive review explores the emerging field of epigenetics in intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (aSAH). Despite recent advancements, the high mortality of aSAH needs an understanding of its underlying pathophysiology, where epigenetics plays a crucial role. This review synthesizes the current knowledge, focusing on three primary epigenetic mechanisms: DNA methylation, non-coding RNA (ncRNA), and histone modification in IA and aSAH. While DNA methylation studies are relatively limited, they suggest a significant role in the pathogenesis and prognosis of IA and aSAH, highlighting differentially methylated positions in genes presumably involved in these pathologies. However, methodological limitations, including small sample sizes and a lack of diverse population studies, temper these results. The role of ncRNAs, particularly miRNAs, has been more extensively studied, but there are still few studies focused on histone modifications. Despite methodological challenges and inconsistent findings, these studies underscore the involvement of miRNAs in key pathophysiological processes, including vascular smooth muscle regulation and the inflammatory response. This review emphasizes methodological challenges in epigenetic research, advocating for large-scale epigenome-wide association studies integrating genetic and environmental factors, along with longitudinal studies. Such research could unravel the complex mechanisms behind IA and aSAH, guiding the development of targeted therapeutic approaches.

Platinum iodido drugs show potential anti-tumor activity, affecting cancer cell metabolism and inducing ROS and senescence in gastrointestinal cancer cells.

Cisplatin-based chemotherapy has associated clinical disadvantages, such as high toxicity and resistance. Thus, the development of new antitumor metallodrugs able to overcome different clinical barriers is a public healthcare priority. Here, we studied the mechanism of action of the isomers trans and cis-[PtI2(isopropylamine)2] (I5 and I6, respectively) against gastrointestinal cancer cells. We demonstrate that I5 and I6 modulate mitochondrial metabolism, decreasing OXPHOS activity and negatively affecting ATP-linked oxygen consumption rate. Consequently, I5 and I6 generated Reactive Oxygen Species (ROS), provoking oxidative damage and eventually the induction of senescence. Thus, herein we propose a loop with three interconnected processes modulated by these iodido agents: (i) mitochondrial dysfunction and metabolic disruptions; (ii) ROS generation and oxidative damage; and (iii) cellular senescence. Functionally, I5 reduces cancer cell clonogenicity and tumor growth in a pancreatic xenograft model without systemic toxicity, highlighting a potential anticancer complex that warrants additional pre-clinical studies.

Application of Nuclear Medicine Techniques in Musculoskeletal Infection: Current Trends and Future Prospects.

Nuclear medicine has become an indispensable discipline in the diagnosis and management of musculoskeletal infections. Radionuclide tests serve as a valuable diagnostic tool for patients suspected of having osteomyelitis, spondylodiscitis, or prosthetic joint infections. The choice of the most suitable imaging modality depends on various factors, including the affected area, potential extra osseous involvement, or the impact of previous bone/joint conditions. This review provides an update on the use of conventional radionuclide imaging tests and recent advancements in fusion imaging scans for the differential diagnosis of musculoskeletal infections. Furthermore, it examines the role of radionuclide scans in monitoring treatment responses and explores current trends in their application. We anticipate that this update will be of significant interest to internists, rheumatologists, radiologists, orthopedic surgeons, rehabilitation physicians, and other specialists involved in musculoskeletal pathology.

Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis.

Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, ß-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.

The influence of epigenetic biological age on key complications and outcomes in aneurysmal subarachnoid haemorrhage.

BACKGROUND: We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality. METHODS: We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum's, Horvath's, Levine's and both versions of Zhang's clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3-5) and mortality using linear regression models adjusted for confounders. RESULTS: Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath's and Levine's clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum's clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks. CONCLUSIONS: Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes.

[Consensus on criteria and minimum data set for the referral of candidate patients for home enteral nutrition teleconsultation: TELENUT project]. / Consenso sobre criterios y conjunto mínimo de datos para la derivación de pacientes candidatos a teleconsulta de nutrición enteral domiciliaria: proyecto TELENUT.

INTRODUCTION: teleconsultation is a useful healthcare tool in the multidisciplinary management of patients with indications of home enteral nutrition (HEN). The use of different teleconsultation platforms, as it happens in the Andalusian Health System (SAS), results in heterogeneous referral processes between Primary Care and hospital services in the same region. OBJECTIVES: to establish a consensus on patient profiles and the minimum data set necessary to guarantee an adequate referral to NED teleconsultation regardless of the existing platform. These agreed aspects in Andalusia can serve as a reference in other regions. METHODS: three consecutive steps were followed: a) non-systematic review of the indexed literature on teleconsultation in clinical nutrition in Spain; b) survey to know the implementation and unmet needs of teleconsultation platforms in Andalusian public hospitals; and c) working meetings and consensus of 14 health professionals of Primary Care (n = 4) and endocrinology and hospital clinical nutrition (n = 10). RESULTS: three referral forms were agreed in which three patient profiles were defined, with the corresponding minimum set of data necessary to request NED teleconsultation. The Primary Care team should provide this set of data to the clinical nutrition specialist via a teleconsultation platform, implemented in the SAS. CONCLUSIONS: three agreed forms between healthcare professionals involved in the referral process serve to standardize the request for teleconsultation of NED between healthcare teams based on patient profiles.

Factors associated with the use of medicines and self-medication during the COVID-19 pandemic in 12 Latin American countries.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has triggered a rise in the global phenomenon of self-medication. The use of medicines with unsubstantiated claims of benefit for the prevention and/or treatment of infected people has been widely adopted. Objective: To determine the factors associated with the use of medicines and self-medication by Latin American populations during the COVID-19 pandemic. Methods: This analytical cross-sectional study was conducted via an analysis of secondary data collected from 8777 responses from 12 Latin American countries obtained from a survey on the use of medicines and self-medication during the pandemic. Results: Respondents who reported using Paracetamol, Ibuprofen, or antibiotics (ABx) disclosed this as self-medication in 26.9%, 16.6%, and 9.7% of cases respectively. In our multivariate analysis, significant associations were found between: self-medication by individual choice and the use of Hydroxychloroquine, ABx, or non-steroidal anti-inflammatory drugs (NSAIDs) (p = 0.026, = 0.003, and <0.001 respectively); self-medication on the recommendation of a family member, with ABx, Paracetamol, Ibuprofen, or other NSAIDs (p <0.001, <0.001, <0.001, and <0.001 respectively); and self-medication on the recommendation of another person, with Chloroquine, Hydroxychloroquine, Azithromycin, Penicillin, other ABx, Warfarin, Ivermectin, Paracetamol, Ibuprofen, or other NSAIDs (p <0.001, <0.001, <0.001, = 0.001, <0.001, <0.001, = 0.004, <0.001, <0.001, and <0.001 respectively). Conclusion: There was a significantly high prevalence of self-medication in our Latin American study population, including the use of medicines not recommended for COVID-19 treatment and/or prevention. The implementation of public health measures aimed at combating the worrying COVID-19 infodemic is essential to prevent this ongoing issue and its associated negative impacts on both current public health and future medication efficacy. This is especially important in the case of ABx due to the threat of a future antimicrobial resistance pandemic.

Improving the Access of Highly Sensitized Patients to Kidney Transplantation From Deceased Donors: The Spanish PATHI Program With Allocation Based on the Virtual Crossmatch.

BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018. One-year graft and patient survival and acute rejection were also measured. A Cox model was used to identify factors related to patient death and graft loss and logistical regression for those associated with rejection. RESULTS: One thousand eighty-nine patients were included, and 272 (25%) were transplanted. Transplant rate by cPRA was 54.9%, 40.5%, and 12.8% in patients with cPRA98%, cPRA99%, and cPRA100%, respectively. One-year patient survival was 92.5%. Recipient age ≥60, time under dialysis >7 y, and delayed graft function were mortality risk factors. One-year graft survival was 88.7%. The factor related to graft loss was delayed graft function. The rejection rate was 22%. Factors related to rejection were sex, older recipients, and posttransplant donor-specific antibodies. CONCLUSIONS: A prioritization approach increases transplant options for highly sensitized patients with appropriate short-term postransplant outcomes. Along with other programs, PATHI may inspire other countries to adopt strategies to meet transplant needs of these patients.

Implementation of pure shift 1 H NMR in metabolic phenotyping for structural information recovery of biofluid metabolites with complex spin systems.

NMR spectroscopy is a mainstay of metabolic profiling approaches to investigation of physiological and pathological processes. The one-dimensional proton pulse sequences typically used in phenotyping large numbers of samples generate spectra that are rich in information but where metabolite identification is often compromised by peak overlap. Recently developed pure shift (PS) NMR spectroscopy, where all J-coupling multiplicities are removed from the spectra, has the potential to simplify the complex proton NMR spectra that arise from biosamples and hence to aid metabolite identification. Here we have evaluated two complementary approaches to spectral simplification: the HOBS (band-selective with real-time acquisition) and the PSYCHE (broadband with pseudo-2D interferogram acquisition) pulse sequences. We compare their relative sensitivities and robustness for deconvolving both urine and serum matrices. Both methods improve resolution of resonances ranging from doublets, triplets and quartets to more complex signals such as doublets of doublets and multiplets in highly overcrowded spectral regions. HOBS is the more sensitive method and takes less time to acquire in comparison with PSYCHE, but can introduce unavoidable artefacts from metabolites with strong couplings, whereas PSYCHE is more adaptable to these types of spin system, although at the expense of sensitivity. Both methods are robust and easy to implement. We also demonstrate that strong coupling artefacts contain latent connectivity information that can be used to enhance metabolite identification. Metabolite identification is a bottleneck in metabolic profiling studies. In the case of NMR, PS experiments can be included in metabolite identification workflows, providing additional capability for biomarker discovery.

Cyber sexual harassment against women and impact on health. A cross-sectional study in a representative population sample.

BACKGROUND: This study focuses on the frequency of cyber sexual harassment (CSH) and examines its link with five health impact indicators (self-perceived health, medication, suicidal ideation, suicide attempts and use of health services). METHODS: Analyzing the data provided by the 2019 Macro-survey on violence against women in Spain, two items of which refer to CSH. It was conducted in Spain on a representative sample of 9568 women aged over 16 years old. RESULTS: A total of 9.15% of the women surveyed had experienced CSH at some point in their lives. Being under 25 years old, having higher education, not being in a relationship, having no religious beliefs and having a certified disability are sociodemographic characteristics associated with a higher risk of CSH. Women who have experienced other forms of gender-based violence also show an increased risk. Female victims of CSH reported higher rates of suicidal ideation (20% versus 9.79% in non-victims of CSH) and suicidal attempts (7.20% versus 1.74% in non-victims of CSH). CONCLUSIONS: These findings have significant implications for the design of preventive health polices, which should incorporate strategies to address CSH as part of the continuum of multiple interrelated forms of gender violence that affect women and girls throughout their lives.