High Morbidity Research Articles

Plasma proteometabolome in lung cancer: exploring biomarkers through bidirectional Mendelian randomization and colocalization analysis.

Unlike other cancers with widespread screening (breast, colorectal, cervical, prostate, and skin), lung nodule biopsies for positive screenings have higher morbidity with clinical complications. Development of non-invasive diagnostic biomarkers could thereby significantly enhance lung cancer management for at-risk patients. Here, we leverage Mendelian Randomization (MR) to investigate the plasma proteome and metabolome for potential biomarkers relevant to lung cancer. Utilizing bidirectional MR and co-localization analyses, we identify novel associations, highlighting inverse relationships between plasma proteins SFTPB and KDELC2 in lung adenocarcinoma (LUAD) and positive associations of TCL1A with lung squamous cell carcinoma (LUSC) and CNTN1 with small cell lung cancer (SCLC). Additionally, our work reveals significant negative correlations between metabolites such as theobromine and paraxanthine, along with paraxanthine-related ratios, in both LUAD and LUSC. Conversely, positive correlations are found in caffeine/paraxanthine and arachidonate (20:4n6)/paraxanthine ratios with these cancer types. Through single-cell sequencing data of normal lung tissue, we further explore the role of lung tissue-specific protein SFTPB in carcinogenesis. These findings offer new insights into lung cancer etiology, potentially guiding the development of diagnostic biomarkers and therapeutic approaches.

Childhood interstitial lung diseases: current understanding of the classification and imaging findings.

Childhood interstitial lung diseases (chILDs) encompass a diverse group of disorders with a high mortality rate and severe respiratory morbidities. Recent investigations have revealed that the classification of adult ILDs is not valid for chILDs, particularly for ILDs of early onset. Therefore, Children's Interstitial Lung Disease Research Cooperative of North America proposed a new classification of chILDs for affected children under 2years of age, and later another classification for affected individuals between 2 and 18years of age. In this review, we provide an overview of the imaging findings of chILDs by classification. Most infantile ILDs have unique clinical, radiological, and molecular findings, while the manifestation of pediatric ILDs overlaps with that of adult ILDs.

The dual role of FSP1 in programmed cell death: resisting ferroptosis in the cell membrane and promoting necroptosis in the nucleus of THP-1 cells

BackgroundAcute monocytic leukemia-M5 (AML-M5) remains a challenging disease due to its high morbidity and poor prognosis. In addition to the evidence mentioned earlier, several studies have shown that programmed cell death (PCD) serves a critical function in treatment of AML-M5. However, the role and relationship between ferroptosis and necroptosis in AML-M5 remains unclear.MethodsTHP-1 cells were mainly treated with Erastin and IMP-366. The changes of ferroptosis and necroptosis levels were detected by CCK-8, western blot, quantitative real-time PCR, and electron microscopy. Flow cytometry was applied to detect the ROS and lipid ROS levels. MDA, 4-HNE, GSH and GSSG were assessed by ELISA kits. Intracellular distribution of FSP1 was studied by immunofluorescent staining and western blot.ResultsThe addition of the myristoylation inhibitor IMP-366 to erastin-treated acute monocytic leukemia cell line THP-1 cell not only resulted in greater susceptibility to ferroptosis characterized by lipid peroxidation, glutathione (GSH) depletion and mitochondrial shrinkage, as the FSP1 position on membrane was inhibited, but also increased p-RIPK1 and p-MLKL protein expression, as well as a decrease in caspase-8 expression, and triggered the characteristic necroptosis phenomena, including cytoplasmic translucency, mitochondrial swelling, membranous fractures by FSP1 migration into the nucleus via binding importin α2. It is interesting to note that ferroptosis inhibitor fer-1 reversed necroptosis.ConclusionWe demonstrated that inhibition of myristoylation by IMP-366 is capable of switching ferroptosis and ferroptosis-dependent necroptosis in THP-1 cells. In these findings, FSP1-mediated ferroptosis and necroptosis are described as alternative mechanisms of PCD of THP-1 cells, providing potential therapeutic strategies and targets for AML-M5.

Enzymatic testing for mucopolysaccharidosis type I in Kuwaiti newborns: a preliminary study toward newborn screening

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in the IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and non-specific symptoms, which result in high morbidity and mortality. The incidence of MPS I is unknown in Kuwait. This pilot study was undertaken to screen MPS I in all Kuwaiti neonates born at Farwaniya Hospital (FH), a major center in Kuwait, over 12 months. This study examined the incidence of MPS I for inclusion in the national newborn screening (NBS) to enable its early detection and adequate treatment. All Kuwaiti neonates born at FH between December 2021 and December 2022 were screened for MPS I. The screening consisted of determining IDUA enzyme activity in dried blood spot-derived samples using tandem mass spectrometry. A follow-up genetic analysis of the IDUA gene has been planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. A total of 618 newborns, including 331 (54%) boys and 287 (46%) girls, were screened. Of them, 20 had deficient IDUA enzyme activity but showed negative genetic testing. However, we have diagnosed one additional female infant with MPS I who belonged to FH, but the parents chose to deliver in a private hospital. The molecular genetic study revealed the presence of a previously reported pathogenic nonsense variant in the IDUA c.1882C>T, which is associated with severe phenotype. That being included, MPS I is estimated to be approximately 0.2% of all screened cases in Kuwait. Our study is the first to evaluate the incidence of MPS I in Kuwait. Given the single center, small number of screened infants, and the short study duration thus far, it is premature to calculate the incidence. It is anticipated that as the study continues, we would be able to estimate the incidence in our population correctly. Screening newborns in all maternity hospitals in Kuwait is necessary to calculate the actual incidence of this severe disorder. Still, our preliminary data support the inclusion of MPS I in national NBS program to allow early initiation of treatment and thus improve disease outcome.

CD147 TagSNP is associated with the vulnerability to lung cancer in the Chinese population: a case–control study

BackgroundLung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of developing lung cancer in the Han Chinese population.MethodsA hospital-based case–control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses.ResultsBaseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype.ConclusionsCD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.

Exploring TRIM proteins’ role in antiviral defense against influenza A virus and respiratory coronaviruses

Numerous tripartite motif (TRIM) proteins, identified as E3 ubiquitin ligases, participate in various viral infections through ubiquitylation, ISGylation, and SUMOylation processes. Respiratory viruses, particularly influenza A virus (IAV) and respiratory coronaviruses (CoVs), have severely threatened public health with high morbidity and mortality, causing incalculable losses. Research on the regulation of TRIM proteins in respiratory virus infections is crucial for disease prevention and control. This review introduces TRIM proteins, summarizes recent discoveries regarding their roles and molecular mechanisms in IAV and CoVs infections, discusses current research gaps, and explores potential future trends in this rapidly developing field. It aims to enhance understanding of virus–host interactions and inform the development of new molecularly targeted therapies.

A contemporary view on vascular resections and reconstruction during hepatectomies.

Oncological hepatic surgery carries the possibility to perform vascular reconstructions for advanced tumours with vessel invasion since surgery often represents the only potentially curative approach for these tumours. An extended review was conducted in an attempt to understand and clarify the latest trends in hepatectomies with vascular resections. We searched bibliographic databases including PubMed, Scopus, references from bibliographies and Cochrane Library. Information and outcomes from worldwide clinical trials were collected from qualified institutions performing hepatectomies with vascular resection and reconstruction. Careful patient selection and thorough preoperative imaging remain crucial for correct and safe surgical planning. A literature analysis shows that vascular resections carry different indications in different diseases. Despite significant advances made in imaging techniques and technical skills, reports of hepatectomies with vascular resections are still associated with high postoperative morbidity and mortality. The trend of complex liver resection with vascular resection is constantly on the increase, but more profound knowledge as well as further trials are required. Recent technological developments in multiple fields could surely provide novel approaches and enhance a new era of digital imaging and intelligent hepatic surgery.

Ambulatory bariatric surgery: a prospective single-center experience.

Ambulatory bariatric surgery has recently gained interest especially as a potential way to improve access for eligible patients with severe obesity. Building on our previously published research, this follow-up study delves deeper in the evolving landscape of ambulatory bariatric surgery over a 3-year period, focusing on predictors of success/failure. In a prospective single-center follow-up study, we conducted a descriptive assessment of all eligible patients as per our established protocol, who underwent a planned same-day discharge (SDD) primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between 03/01/2021 and 02/29/2024. Trends in SDD surgeries over time were assessed over six discrete 6month intervals. Primary endpoint was defined as a successful discharge on the day of surgery without emergency department visit or readmission within 24h. Secondary outcomes included 30-day postoperative morbidity. A total of 811 primary SG and 325 RYGB procedures were performed during the study period. Among them, 30% (n = 244) were SDD-SGs and 6% (n = 21) were SDD-RYGBs, respectively. At baseline, median age of the entire SDD cohort was 43years old, 81% were females, and body mass index (BMI) was 44.5kg/m2. The planned SDD approach was successful in 89% after SG (n = 218/244) and in 90% after RYGB (n = 19/21). Nausea/vomiting was the main reason for a failed SDD approach after SG (46%). The 30-day readmission rate was 1.5% (n = 4) for the entire SDD cohort including only one readmission in the first 24h. The percentage of SDD-SGs performed as a proportion of total SGs increased over the initial five consecutive six-month intervals (14%, 25%, 24%, 38%, and 49%). Our SDD protocol for bariatric surgery demonstrates a favorable safety profile, marked by high success rate and low postoperative morbidity. These outcomes have led to a continued increase in ambulatory procedures performed over time especially SG.

Physical restraint and associated agitation.

Physical restraint of patients in intensive care units (ICUs) has an estimated prevalence of 50%. Many medical centres do not have specific protocols for physical restraint, and the decision of whether to physically restrain a patient is up to the nursing staff. Disadvantages of physical restraint include injuries, exacerbation of agitation and an increased risk of developing post-traumatic stress disorder (PTSD). To report prevalence and outcomes in terms of morbidity and mortality of physical restraint in general ICU patients in an 800-bed secondary medical centre. This retrospective study included 647 patients admitted to a general ICU in an 800-bed secondary medical centre in Kfar Saba, Israel, between January and December 2020. Data included demographics, medical history, length of stay, need for mechanical ventilation, number of ventilation days, 28-day mortality, reason for admission, agitation rate assessed by Richmond Agitation and Sedation Scale (RASS) score, need for physical restraint and need for anti-psychotics. Among the patients, 40% (256 of 647) required physical restraint. Older adult patients had a greater likelihood of being physically restrained along with those admitted because of sepsis or acute respiratory failure. Among the study sample, 11% (71 of 647) required anti-psychotics. Patients who were restrained had longer duration of ventilation (5.9 ± 8.2 vs. 0.36 ± 1.4 days; p < .001) and higher 28-day mortality (0.26 ± 0.45 vs. 0.07 ± 0.25, Z = 6.86, p < .001). There was no difference in medical history, except for chronic drug abuse, which was more frequent in the restraint group (18 [6.9%] vs. 11 [2.8%], respectively; p = .019), as well as the use of anti-psychotic medications (24 [9.3%] vs. 19 [4.8%], respectively; p = .034) and anti-depressants (55 [21.2%] vs. 59 [14.8%], respectively; p = .042). The restraint group had higher disease severity scores, as reflected in requirements for vasopressor support (174 [67.2%] vs. 69 [17.3%], respectively; p < .001) and need for dialysis (39 [15.1%] vs. 19 [4.8%], respectively; p < .001); higher frequency of in-hospital anti-psychotic treatment (60 [23.2%] vs. 11 [2.8%], respectively; p < .001); a greater tendency for agitation events and more severe agitation scores (episodes of RASS above zero [1.7 ± 4.0 vs. 0.04 ± 0.27, respectively; p < .001] and maximum RASS score [0.19 ± 1.6 vs. 0.01 ± 0.54, respectively; p < .001]). Overall, advanced age, number of ventilation days and need for dialysis were associated with increased 28-day mortality. In the restraint group, advanced age, chronic use of diuretics and the use of dialysis during ICU admission were associated with increased mortality risk. Restrained patients tended to have higher morbidity and mortality during ICU and hospital stays, as well as a greater tendency for agitation events and more severe agitation scores, with an increased need for in-hospital anti-psychotic treatment. These findings regarding patient characteristics might be used to formulate treatment plans to reduce the rate of physical restraint in the ICU. Because restrained ICU patients tend to have higher morbidity and mortality, treatment plans should be formulated to reduce the rate of physical restraint in the ICU. NCT04771793.

Re-evaluation of risk and oncological outcomes of resection of veins and arteries in the resection of pancreatic cancer.

Advances in chemotherapy have led to increasing major vascular resection during pancreatectomy which has been contraindicated due to high morbidity. This study aimed to verify the safety and oncological outcomes of vascular resection during pancreatectomy in the era of neoadjuvant therapy. Data from patients who underwent surgery for pancreatic cancer at Seoul National University Hospital between 2001 and 2021 were reviewed. Clinicopathological outcomes were analyzed according vessel resection. A propensity-score-matched (PSM) analysis was performed to evaluate survival outcomes. Of 1596 patients, the proportion of those who underwent vascular resection increased from 9.2% to 23.4% over time divided into 5-year intervals. There were no differences in major complications (15.6% vs. 13.0%; p = .266) and 30-day mortality rate (0.3% vs. 0.6%; p = .837) between the vascular and nonvascular resection groups. After PSM, the vascular resection group demonstrated comparable survival outcome with the nonvascular resection group (5 year-survival-rate 20.4 vs. 23.7%; p = .194). Arterial resection yielded comparable survival outcome with nonvascular resection (5 year-survival-rate 38.1% vs. 23.7%; p = .138). Appropriate vascular resection-even arterial-is safe and effective in patients carefully selected for radical surgery in the era of neoadjuvant therapy. Further studies are needed to determine the optimal indication and method for vascular resection in patients with pancreatic cancer.

Designing multi-epitope vaccine against human cytomegalovirus integrating pan-genome and reverse vaccinology pipelines

Human cytomegalovirus (HCMV) is accountable for high morbidity in neonates and immunosuppressed individuals. Due to the high genetic variability of HCMV, current prophylactic measures are insufficient. In this study, we employed a pan-genome and reverse vaccinology approach to screen the target for efficient vaccine candidates. Four proteins, envelope glycoprotein M, UL41A, US23, and US28, were shortlisted based on cellular localization, high solubility, antigenicity, and immunogenicity. A total of 29 B-cell and 44 T-cell highly immunogenic and antigenic epitopes with high global population coverage were finalized using immunoinformatics tools and algorithms. Further, the epitopes that were overlapping among the finalized B-cell and T-cell epitopes were linked with suitable linkers to form various combinations of multi-epitopic vaccine constructs. Among 16 vaccine constructs, Vc12 was selected based on physicochemical and structural properties. The docking and molecular simulations of VC12 were performed, which showed its high binding affinity (−23.35 kcal/mol) towards TLR4 due to intermolecular hydrogen bonds, salt bridges, and hydrophobic interactions, and there were only minimal fluctuations. Furthermore, Vc12 eliciting a good response was checked for its expression in Escherichia coli through in silico cloning and codon optimization, suggesting it to be a potent vaccine candidate.

Development of optimized resveratrol/piperine-loaded phytosomal nanocomplex for isoproterenol-induced myocardial infarction treatment

Cardiovascular disease is a significant and ever-growing concern, causing high morbidity and mortality worldwide. Conventional therapy is often very precarious and requires long-term usage. Several phytochemicals, including Resveratrol (RSV) and Piperine (PIP), possess significant cardioprotection and may be restrained in clinical settings due to inadequate pharmacokinetic properties. Therefore, this study strives to develop an optimized RSV phytosomes (RSVP) and RSV phytosomes co-loaded with PIP (RPP) via solvent evaporation method using Box-Behnken design to enhance the pharmacokinetic properties in isoproterenol-induced myocardial infarction (MI). The optimized particle size (20.976 ± 0.39 and 176.53 ± 0.88 nm), zeta potential (−33.33 ± 1.5 and −48.7 ± 1.6 mV), drug content (84.57 ± 0.9 and 87.16 ± 0.6%), and %EE (70.56 ± 0.7 and 67.60 ± 0.57%) of the prepared RSVP and RPP, respectively demonstrated enhanced solubility and control release in diffusion media. The oral administration of optimized RSVP and RPP in myocardial infarction-induced rats exhibited significant (p < 0.001) improvement in heart rate, ECG, biomarker, anti-oxidant levels, and no inflammation than pure RSV. The pharmacokinetic assessment on healthy Wistar rats exhibited prolonged circulation (>24 h) of RSVP and RPP compared to free drug/s. The enhanced ability of RSVP and RPP to penetrate bio-membranes and enter the systemic circulation renders them a more promising strategy for mitigating MI.

Comprehensive Quality Analysis of Conventional and Novel Biomarkers in Diagnosing and Predicting Prognosis of Coronary Artery Disease, Acute Coronary Syndrome, and Heart Failure, a Comprehensive Literature Review.

Coronary artery disease (CAD), acute coronary syndrome (ACS), and heart failure (HF) are major global health issues with high morbidity and mortality rates. Biomarkers like cardiac troponins (cTn) and natriuretic peptides (NPs) are crucial tools in cardiology, but numerous new biomarkers have emerged, proving increasingly valuable in CAD/ACS. These biomarkers are classified based on their mechanisms, such as fibrosis, metabolism, inflammation, and congestion. The integration of established and emerging biomarkers into clinical practice is an ongoing process, and recognizing their strengths and limitations is crucial for their accurate interpretation, incorporation into clinical settings, and improved management of CVD patients. We explored established biomarkers like cTn, NPs, and CRP, alongside newer biomarkers such as Apo-A1, IL-17E, IgA, Gal-3, sST2, GDF-15, MPO, H-FABP, Lp-PLA2, and ncRNAs; provided evidence of their utility in CAD/ACS diagnosis and prognosis; and empowered clinicians to confidently integrate these biomarkers into clinical practice based on solid evidence.

Orchestration of antiviral responses within the infected central nervous system.

Many newly emerging and re-emerging viruses have neuroinvasive potential, underscoring viral encephalitis as a global research priority. Upon entry of the virus into the CNS, severe neurological life-threatening conditions may manifest that are associated with high morbidity and mortality. The currently available therapeutic arsenal against viral encephalitis is rather limited, emphasizing the need to better understand the conditions of local antiviral immunity within the infected CNS. In this review, we discuss new insights into the pathophysiology of viral encephalitis, with a focus on myeloid cells and CD8+ T cells, which critically contribute to protection against viral CNS infection. By illuminating the prerequisites of myeloid and T cell activation, discussing new discoveries regarding their transcriptional signatures, and dissecting the mechanisms of their recruitment to sites of viral replication within the CNS, we aim to further delineate the complexity of antiviral responses within the infected CNS. Moreover, we summarize the current knowledge in the field of virus infection and neurodegeneration and discuss the potential links of some neurotropic viruses with certain pathological hallmarks observed in neurodegeneration.

Utilizing Agricultural By-Products for Sustainable Agouti (Dasyprocta leporina) Diets: Evaluating Low-Cost Feed Alternatives in Trinidad and Tobago, West Indies

The agouti (Dasyprocta leporina) is a promising protein source in the Caribbean, Mexico, and South America. This study assessed the impact of three by-product diet formulations on intensively reared agoutis, including a cost analysis and nutritional evaluation as well as the nutritional composition, digestibility, and economic viability of three experimental diets. Sixteen adult male agoutis were individually housed at the University of the West Indies’ Field Station. After a two-week acclimatization, a four-week data collection phase followed. The four treatments included a control diet of commercial rabbit pellets and three experimental diets with varying by-product ratios. Key findings revealed that Treatment 2 had elevated Dry Matter, Crude Fat, and fiber but potentially compromised digestibility due to higher fiber and lignin. Treatment 1 resulted in the highest morbidity and was discontinued after two weeks due to significant weight loss but demonstrated the most cost-effective results, with the lowest variable cost per 45 kg, the lowest feeding cost to reach 3 kg, and the highest gross margin. Treatment 2 effectively maintained animal weight. Treatment 3 showed promising growth due to low levels of Neutral Detergent Fiber (NDF) and Acid Detergent Lignin (ADL). Alternative dietary feedstuffs from agricultural by-products show potential for sustaining body weight in adult male agoutis, but further research is needed to refine nutritional requirements for growing agoutis.

Chimeric antigen receptor adoptive immunotherapy in central nervous system tumors: state of the art on clinical trials, challenges, and emerging strategies to addressing them.

Central nervous system (CNS) tumors represent a significant unmet medical need due to their enduring burden of high mortality and morbidity. Chimeric antigen receptor (CAR) T-cell therapy emerges as a groundbreaking approach, offering hope for improved treatment outcomes. However, despite its successes in hematological malignancies, its efficacy in solid tumors, including CNS tumors, remains limited. Challenges such as the intricate tumor microenvironment (TME), antigenic heterogeneity, and CAR T-cell exhaustion hinder its effectiveness. This review aims to explore the current landscape of CAR T-cell therapy for CNS tumors, highlighting recent advancements and addressing challenges in achieving therapeutic efficacy. Innovative strategies aim to overcome the barriers posed by the TME and antigen diversity, prevent CAR T-cell exhaustion through engineering approaches and combination therapies with immune checkpoint inhibitors to improving treatment outcomes. Researchers have been actively working to address these challenges. Moreover, addressing the unique challenges associated with neurotoxicity in CNS tumors requires specialized management strategies. These may include the development of grading systems, monitoring devices, alternative cell platforms and incorporation of suicide genes. Continued research efforts and clinical advancements are paramount to overcoming the existing challenges and realizing the full potential of CAR T-cell therapy in treating CNS tumors.

Ecuadorian Provinces with High Morbidity and Mortality Rates Due to Asthma among the Working-Age Population: An Ecological Study to Promote Respiratory Health

Ecuadorian Provinces with High Morbidity and Mortality Rates Due to Asthma among the Working-Age Population: An Ecological Study to Promote Respiratory Health

Complex intracranial aneurysms: a DELPHI study to define associated characteristics.

Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA. An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability. In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac. The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach.

Preoperative in-hospital delay increases postoperative morbidity and mortality in patients with acute appendicitis: A meta-analysis.

Complicated appendicitis is associated with high morbidity, mortality, and healthcare costs. However, the relationship of preoperative in-hospital delay >24 hours with complicated appendicitis and postoperative morbidity remains unclear. This meta-analysis investigated the effects of preoperative in-hospital delay on complicated appendicitis and postoperative morbidity in patients with acute appendicitis. This study adheres to the PRISMA 2020 and AMSTAR 2 guidelines. The PubMed, Embase, Cochrane Library, and Web of Science databases up to October 14, 2023 (updated on March 16, 2024) were searched for randomized controlled trials (RCTs) and observational studies that evaluated the effect of preoperative in-hospital delays of >24 hours on acute appendicitis. Odds ratios (OR) and 95% confidence intervals were also determined. We yielded 18,130 records, of which 28 studies (512,881 patients) were included in the meta-analysis. The risk of bias was considered serious, moderate, and low for 24, 3, and 1 study, respectively. Although preoperative in-hospital delays of >24 hours were not associated with a higher risk of surgical site infection (OR 1.04, 95% CI 0.97, 1.12, P=0.25), in-hospital delays of >24 hours was a risk factor for complicated appendicitis (OR 1.60, 95% CI 1.25, 2.05, P=0.0002), and postoperative complications (OR 1.51, 95% CI 1.30, 1.75, P<0.00001). In addition, an in-hospital delay of >24 hours before surgery increased the OR of postoperative mortality (OR 1.81, 95% CI 1.33, 2.45, P=0.0001). The sensitivity analyses also confirmed the robustness of our results. An in-hospital delay of >24 hours is a risk factor for complicated appendicitis, postoperative complications, and mortality. Given the subsequent adverse outcomes of in-hospital delays, appendectomy should not be delayed for >24 hours.

Hospital outcomes of acute COVID-19 infection among patients with neurological conditions: a single-center study

BackgroundCoronavirus disease 2019 (COVID-19) infection has been associated with severe neurological consequences, including stroke or seizures, and less severe neurological sequelae, including headaches, dizziness, and anosmia. Earlier COVID-19 variants were associated with high morbidity and mortality; however, knowledge of the impact of neurological conditions in the setting of COVID-19 on healthcare outcomes is limited. We sought to determine the impact of acute neurological conditions and acute COVID-19 infection on inpatient hospitalization outcomes.MethodsThis was a retrospective, observational study of adult patients who were admitted to a large academic medical center in the Southeastern US between April 2020 and December 2021 with acute COVID-19 infection and a neurological diagnosis. Patient demographics, medical history, neurological diagnoses, and hospitalization outcomes were obtained from the medical record. Descriptive statistics and unadjusted and adjusted logistic regression analyses were performed.ResultsOf the 1,387 patients included in this study, 27% died and 23% were kept under ventilation during hospitalization. The mean +/− standard deviation (SD) age was 64.6+/−16.9 years, with 52.8% women and 30.1% identifying as Black/African American. The most common neurological conditions included ischemic stroke (35.0%), movement disorder (12.0%), and hemorrhagic stroke (10.7%). In-hospital death was most common among those with epilepsy (p = 0.024), headache (p = 0.026), and dementia (p &amp;lt; 0.0001) compared to individuals without those conditions. Ventilation support was given more commonly to dementia patients (p = 0.020). Age was a significant risk factor for death (p &amp;lt; 0.001) and hospital length of stay (LOS) for ventilation (p &amp;lt; 0.001), but no neurological condition was a significant factor in adjusted logistic regression analyses.DiscussionMortality was high in this study, with more than one-quarter of patients dying in the hospital. Death was the most common among those with epilepsy, headache, or dementia, but no neurological condition increased the risk of in-hospital mortality or ventilation. Future studies would determine the long-term neurological sequelae of those discharged from the hospital with COVID-19 and a neurological condition.