The impact of serum albumin levels on postoperative complications in lumbar and cervical spine surgery: an analysis of the Michigan Spine Surgery Improvement Collaborative registry.

OBJECTIVE: Patients with serum albumin levels < 3.5 g/dL are considered malnourished, but there is a paucity of data regarding the outcomes of patients with albumin levels > 3.5 g/dL. The objective of this study was to evaluate the effect of albumin on postoperative outcome in patients undergoing elective cervical and lumbar spine procedures. METHODS: The Michigan Spine Surgery Improvement Collaborative database was queried for lumbar and cervical fusion surgeries between January 2020 and December 2022. Patients were grouped by preoperative serum albumin levels: < 3.5 g/dL, 3.5-3.7 g/dL, 3.8-4.0 g/dL, and > 4.0 g/dL. Primary outcomes included urinary retention, ileus, dysphagia, surgical site infection (SSI), readmission within 30 and 90 days, return to the operating room, and length of stay (LOS) ≥ 4 days. Multivariate analysis was conducted to adjust for potential confounders. RESULTS: This study included 15,629 lumbar cases and 6889 cervical cases. Within the lumbar cohort, an albumin level of 3.5-3.7 g/dL was associated with an increased risk of readmission at 30 days (p = 0.048) and 90 days (p = 0.005) and an LOS ≥ 4 days (p < 0.001). An albumin level of 3.8-4.0 g/dL was associated with an increased risk of an LOS ≥ 4 days (p < 0.001). Within the cervical cohort, an albumin level of 3.5-3.7 g/dL was associated with an increased risk of SSI (p = 0.023), readmission at 30 days (p < 0.002) and 90 days (p < 0.001), return to the operating room (p = 0.002), and an LOS ≥ 4 days (p < 0.001). An albumin level of 3.8-4.0 g/dL was associated with an increased risk of readmission at 30 days (p = 0.012) and 90 days (p = 0.001) and an LOS ≥ 4 days (p < 0.001). CONCLUSIONS: This study maintains that patients with hypoalbunemia undergoing spine surgery are at risk for postoperative adverse events. However, there also exist significant associations between borderline serum albumin levels of 3.5-4.0 g/dL and increased risk of postoperative adverse events.

Incidence of Colorectal Cancer After Intestinal Infection Due to Clostridioides difficile.

Background: Clostridioides difficile (C. difficile or C. diff) is a toxin-producing bacteria that is notorious for causing life-threatening diarrhea. Recent literature has investigated various effects of Clostridioides difficile infection (CDI) in cancer patients, but research into the impact of CDI on the development of cancer and its effects on the microbiome is limited. CDI predominately affects the colon, which urges consideration into the sequalae of infection. This study investigated the correlation between CDI and the incidence of colorectal carcinoma (CRC). Methods: A retrospective study (2010 - 2020) was conducted using a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. The International Classification of Disease ninth and 10th Codes (ICD-9, ICD-10), Current Procedural Terminology (CPT), and National Drug Codes were used to identify CRC diagnosis, CDI, and matching or control parameters. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), region of residence, and CDI treatment. An additional, but separate, query was executed to include obese patients with and without CDI, who were similarly matched and assessed for CRC. Statistical analyses were implemented to assess significance and estimate odds ratios (ORs). Results: CDI was associated with a decreased incidence of CRC (OR = 0.59, 95% confidence interval (CI): 0.55 - 0.63), and the difference was statistically significant (P < 2.2 × 10-16). CDI treatment, including appropriate antibiotics and fecal microbiota transplant (FMT), was controlled for in both infected and noninfected populations. Patients with a prior CDI who received relevant treatment were compared to patients with no history of CDI and received analogous treatment. Both populations subsequently developed CRC. Results remained statistically significant (P < 2.2 × 10-16) with a relative risk (RR) of 0.57 (95% CI: 0.54 - 0.60). Obesity was explored as a controlled variable in relation to CRC development in patients with and without prior CDI. Obese patients without a history of CDI were found to have a decreased risk of developing CRC. Results were statistically significant (P < 4.3 × 10-13) with an OR of 0.70 (95% CI: 0.63 - 0.77). Conclusions: This study shows a statistically significant correlation between CDI and decreased incidence of CRC. Additionally, there is a statistically significant correlation between obese patients with CDI and an increased incidence of CRC. Further research is needed to explore the mechanism of this striking relationship and the implications of CDIs on the microbiome.

Bone Grafting Options for Single-Level TLIF: So Many Options, What Is the Evidence?

BACKGROUND: This review seeks to investigate the clinically relevant bone graft materials in single-level transforaminal lumbar interbody fusion (TLIF) procedures as defined by (1) primary outcomes (ie, fusion rates and complication rates) and (2) patient-reported outcomes (ie, visual analog scale [VAS] and Oswestry disability index [ODI]). Because of the advantages in stimulating bone growth, autologous bone grafts such as the iliac crest bone graft (ICBG) have been the gold standard. Numerous alternatives to ICBG have been introduced. Understanding the risks and benefits of bone graft options is vital to optimizing patient care. METHODS: A PubMed search was performed for all clinical studies published between January 2008 and March 2023 that referenced the single-level TLIF procedure as well as one of the following grafts: autograft, allograft, bone morphogenetic protein (BMP), demineralized bone matrix, or mesenchymal stem cells (MSCs). Case studies and reports were excluded. RESULTS: Twenty-eight studies met the inclusion criteria. Studies from the PubMed search demonstrated similarly high fusion rates across nearly all graft materials, the lone exception being MSCs, which showed lower fusion rates. ICBG grafts experienced higher rates of postoperative graft site pain. The BMP graft material had high rates of radiculitis, heterogeneous ossification, and vertebral osteolysis. Patients saw an overall improvement in VAS and ODI scores with all graft materials. CONCLUSION: Local autografts and ICBG have been the most studied. Fusion rates during single-level TLIF were similar across all graft materials except MSCs. Patient-reported pain levels improved after TLIF surgery regardless of the type of grafts used. While BMP implants have shown promising benefits, they have introduced a new array of complications not normally seen in ICBG implants. The study is limited by the lack of evidence of certain graft materials as well as nonuniformity in metrics evaluating the efficacy of graft materials.

Co-occurrence of glioma and multiple sclerosis: Prevailing theories and emerging therapies.

Though the concurrence of primary brain tumors and multiple sclerosis (MS) is exceedingly rare, instances have been noted in the literature as early as 1949. Given these observations, researchers have proposed various ideas as to how these malignancies may be linked to MS. Due to insufficient data, none have gained traction or been widely accepted amongst neurologists or neuro-oncologists. What is abundantly clear, however, is the mounting uncertainty faced by clinicians when caring for these individuals. Concerns persist about the potential for disease modifying therapies (DMTs) to initiate or promote tumor growth and progression, and to date, there are no approved treatments capable of mitigating both MS disease activity and tumor growth, let alone established guidelines that clinicians may refer to. Collectively, these gaps in the literature impose limitations to optimizing the care and management of this population. As such, our hope is to stimulate further discussion of this topic and prompt future investigations to explore novel treatment options and advance our understanding of these concurrent disease processes. To this end, the chief objective of this article is to evaluate proposed ideas of how the diseases may be linked, outline emerging therapies for both MS and brain tumors, and describe evidence-based approaches to diagnosing and treating this patient population.

Outcomes of HSV-1 encephalitis infection in glioblastoma: An integrated systematic analysis.

INTRODUCTION: Herpes Simplex Virus-1 (HSV-1) is a neurotropic DNA virus with neural latency and stereotypic viral encephalitis. It has been reported to conceal underlying glioblastoma (GBM) due to similar radiographic imaging and clinical presentation. Limited data exist on the co-occurrence of GBM and HSV-1. To better describe the pathophysiology of HSV-1 superinfections in GBM, we performed a comprehensive review of GBM cases with superimposed HSV-1. METHODS: A comprehensive literature search of six electronic databases with apriori search criteria was performed to identify eligible cases of GBM with HSV-1. Relevant clinic-radiographic data were collected, Kaplan-Meier estimates, Fisher's exact test, and logistic regression analyses were used. RESULTS: We identified 20 cases of HSE in GBM with an overall survival (OS) of 8.0 months. The median age of presentation was 63 years (range: 24-78 years) and the median interval between GBM or HSE diagnosis was 2 months (range: 0.05-25 months). HSE diagnosis before GBM diagnosis was a predictor for improved survival (HR: 0.06; 95% CI: [0.01-0.54]; p < 0.01). There is a significant reduction in OS in patients with concomitant HSE and GBM compared to the cancer genome atlas (TCGA) cohort (median OS: 8 months vs. 14.2 months; p < 0.05). Finally, HSV does not directly infect GBM cells but indirectly activates a local immune response in the tumor microenvironment. CONCLUSIONS: Superimposed HSE in GBM may contribute to a significant reduction in OS compared to uninfected controls, potentially activating proto-oncogenes during active infection and latency. Preoperative HSE may induce an antiviral immune response, which may serve as a positive prognostic factor. Prompt antiviral treatment upon co-occurrence is necessary.

Changes in Cerebrovascular Procedures and Outcomes During COVID-19 Using the National Surgery Quality Improvement Project.

OBJECTIVE: Explore the consequences of the coronavirus pandemic (COVID-19) on patients suffering from cerebrovascular disorders necessitating interventions. METHODS: Using the National Surgical Quality Improvement Program database, patients with cerebrovascular disease who underwent procedures before (2018-2019) and during (2020-2021) COVID-19 were identified. ICD-10 and Current Procedure Terminology codes were employed to classify diseases and elective cases, respectively. Our study analyzed variations in diagnoses, procedures, demographics, mortality and morbidity likelihood scores, and outcomes. Analysis was conducted using R 4.2.1 with tidyverse, haven, and Ime4 packages. Statistical significance was defined as P < 0.05. RESULTS: There was a significant rise in cerebrovascular accidents (CVAs) (9.96% vs. 12.28%) and a decrease in elective carotid endarterectomies (92.30% vs. 87.22%). Carotid stenting increased significantly (7.63% vs. 12.62%), and mortality probability scores rose for CVAs and carotid interventions. Ethnic (Hispanic) and racial minorities (Asians and Black/African American) were disproportionately affected (P < 0.001). Conditions from delayed care increased, and total operative times rose (117.46 vs. 124.33 minutes). Various patient outcomes worsened (P < 0.05), and multivariate analyses showed Hispanic patients had higher mortality and morbidity probability scores (P < 0.05). CONCLUSIONS: The pandemic led to more severe disease progression and reduced diagnoses due to screening delays, indicating deferred care. Prolonged operative times, extended hospital stays, and worsening outcomes, including infections and thrombotic events, hint at the repercussions of persistent staff shortages in health care facilities. Ethnic and racial minorities faced disproportionate impacts. To minimize harm to patients with cerebrovascular disease in future public health crises, it is crucial to develop policies that address these findings.

The Role of Hemophilus influenzae Infection and Its Relationship With Colorectal Cancer.

Background: Hemophilus influenzae is a gram-negative coccobacillus. Non-typeable H. influenzae infection is a significant cause of disease that activates the inflammatory pathway involving the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. A gain-of-function mutation in NLRP3 results in cryopyrin-associated periodic syndromes characterized by inflammatory conditions in the lungs, skin, joints, and eyes but not in the gut. This leads to homeostasis of the gut microbiota, which reduces inflammation and may have protective effect against colorectal cancer (CRC). This study aimed to evaluate the correlation between H. influenzae infection and the incidence of CRC. Methods: A retrospective study was conducted from 2010 to 2019 using a HIPAA-compliant national database. ICD-10, ICD-9, CPT, and National Drug Codes were used to identify patients with or without a history of H. influenzae infection. Standard statistical methods were used to analyze the outcomes. Results: The query was analyzed and matched, resulting in 13,610 patients in both groups. The incidence of CRC was 167 and 446 in the H. influenzae and control groups, respectively. The difference was statistically significant with P < 2.2 ×10-16 and an odds ratio of 0.41 (95% confidence interval: 0.36 - 0.47). Additionally, the groups were further evaluated and matched by treatment, which resulted in a statistically significant decrease in CRC incidence in the H. influenzae group. Conclusion: This study showed a statistically significant correlation between H. influenzae and the reduced incidence of CRC. This reduction in CRC in patients with a history of H. influenzae infection suggests a potential link to the NLRP3 inflammasome, which should be further studied.

Human Cytomegalovirus (CMV) Infection Associated With Decreased Risk of Bronchogenic Carcinoma: Understanding How a Previous CMV Infection Leads to an Enhanced Immune Response Against Malignancy.

INTRODUCTION:  ​Cytomegalovirus (CMV) causes a long-lasting, asymptomatic infection that reportedly has both advantageous and deleterious effects on tumor progression. The purpose of this study was to evaluate the correlation between CMV infection and the incidence of bronchogenic carcinoma. METHODS: The study was conducted using a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to identify patients both with and without histories of CMV infection using International Classification of Diseases (ICD-10 and ICD-9) codes. Access to the database was granted by Holy Cross Health, Fort Lauderdale for the purpose of academic research with standard statistical methods used to analyze the data. 14,319 patients were included in both the control and CMV-exposed groups and matched by age range and Charlson Comorbidity Index (CCI) scores. RESULTS: The incidence of bronchogenic carcinoma was 1.69% (243/14,319 patients) in the CMV group and 6.08% (871/14,319 patients) in the control group. The difference was statistically significant by a p-value of less than 2.6x10-16 with an odds ratio of 0.26 (95% CI: 0.24-0.30). The two groups were also matched for treatment. Further evaluation of the CMV-specific treatment effects on outcomes was limited due to the insufficient number of treated patients in the control group. CONCLUSION: This study found a statistically significant correlation between a prior CMV infection and a reduced incidence of bronchogenic carcinoma. This study demonstrates the need for further investigation into how the tumor microenvironment and host immune system are altered by the presence of a latent CMV infection.

Incidence of Breast Cancer and Enterococcus Infection: A Retrospective Analysis.

Background: Enterococci role in the microbiome remains controversial, and researches regarding enterococcal infection (EI) and its sequelae are limited. The gut microbiome has shown to play an important role in immunology and cancer. Recent data have suggested a relationship between the gut microbiome and breast cancer (BC). Methods: Patients in a Health Insurance Portability and Accountability Act (HIPAA) compliant national database (2010 - 2020) were used for this retrospective study. International Classification of Disease (ICD) Ninth and Tenth Codes, Current Procedural Terminology (CPT), and National Drug Codes were used to identify BC diagnosis and EI. Patients were matched for age, sex, Charlson comorbidity index (CCI), antibiotic treatment, obesity, and region of residence. Statistical analyses were implemented to assess significance and estimate odds ratio (OR). Results: EI was associated with a decreased incidence of BC (OR = 0.60, 95% confidence interval (CI): 0.57 - 0.63) and the difference was statistically significant (P < 2.2 × 10-16). Treatment for EI was controlled for in both EI and noninfected populations. Patients with a prior EI and treated with antibiotics were compared to patients with no history of EI and received antibiotics. Both populations subsequently developed BC. Results remained statistically significant (P < 2.2 × 10-16) with an OR of 0.57 (95% CI: 0.54 - 0.60). In addition to standard matching protocol, obesity was controlled for in both groups by exclusively containing obese patients, but one group with prior EI and the other without. In obese patients, a lower incidence of BC was shown in the infected group compared to the noninfected group. Results were statistically significant (P < 2.2 × 10-16) with an OR of 0.56 (95% CI: 0.53 - 0.58). Age of BC diagnosis with and without a prior EI was analyzed and demonstrated increased BC incidence with increasing age in both groups, but less in the EI group. Incidence of BC based on region was analyzed, which showed lower BC incidence across all regions in the EI group. Conclusion: This study shows a statistically significant correlation between EI and decreased incidence of BC. Further exploration is needed to identify and understand not only the role of enterococcus in the microbiome, but also the protective mechanism(s) and impact of EI on BC development.

Vaccination of multiple sclerosis patients during the COVID-19 era: Novel insights into vaccine safety and immunogenicity.

Multiple sclerosis (MS) is an incurable autoimmune disease known to cause widespread demyelinating lesions in the central nervous system (CNS) and a host of debilitating symptoms in patients. The development of MS is believed to be driven by the breakdown of the blood brain barrier, subsequent infiltration by CD4+ and CD8+ T cells, and widespread CNS inflammation and demyelination. Disease modifying therapies (DMTs) profoundly disrupt these processes and therefore compose an essential component of disease management. However, the effects of these therapeutic agents on vaccine safety and immunogenicity in individuals with MS are not yet fully understood. As such, the primary objective of this review article was to summarize the findings of recently conducted studies on vaccine safety and immunogenicity in MS patients treated with DMTs, particularly in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Discussed in this review are vaccinations against influenza, yellow fever, human papillomavirus, measles, mumps, rubella, Streptococcus pneumoniae, hepatitis B, and COVID-19. This article additionally reviews our current understanding of COVID-19 severity and incidence in this patient population, the risks and benefits of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccination guidelines set forth by MS societies and organizations.

Glioblastoma multiforme in patients with human immunodeficiency virus: an integrated review and analysis.

INTRODUCTION: As lifespans for persons living with HIV (PLWH) have improved over the last decade, there has been a simultaneous increase in non-AIDS-related cancer in that group. However, there is a paucity of data regarding the incidence of glioblastoma multiforme (GBM) in PLWH. Better understanding of the oncogenesis, natural history, and treatment outcomes of GBM in PLWH should lead to improved treatment strategies. METHODS: We performed a comprehensive literature search of six electronic databases to identify eligible cases of GBM among PLWH. Kaplan-Meier estimates, Fisher's exact test, and logistic regression were used to interrogate the data. Epidemiologic data on global HIV prevalence was obtained from the 2016 UNAIDS incidence report, and CNS cancer incidence was obtained from the GDB 2016 Brain and Other CNS Cancer Collaborators. RESULTS: There is an inverse relationship between the incidence of HIV and CNS cancer globally. Median overall survival (OS) from GBM diagnosis was 8 months. Estimates for survival at 1 and 2 years were 28 and 5%, respectively. There were no statistically significant predictors of OS in this setting. There was a significant difference (p < 0.01) in OS in PLWH and GBM when compared to TCGA age matched cohorts. CONCLUSION: The diagnosis of GBM in PLWH is severely underreported in the literature. Despite maximal treatment, OS in this patient population is significantly less than in HIV-negative people. There was a poor prognosis of GBM in PLWH, which is inconsistent with previous reports. Further investigation is required for PLWH and concomitant GBM. Analyses must consider if HAART is maintained in PLWH during GBM treatment.

Identification and Characterization of a Minimal Functional Splicing Regulatory Protein, PTBP1.

Polypyrimidine tract binding protein 1 (PTBP1) is a well-studied RNA binding protein that serves as an important model for understanding molecular mechanisms underlying alternative splicing regulation. PTBP1 has four RNA binding domains (RBDs) connected via linker regions. Additionally, PTBP1 has an N-terminal unstructured region that contains nuclear import and export sequences. Each RBD can bind to pyrimidine rich elements with high affinity to mediate splicing activity. Studies support a variety of models for how PTBP1 can mediate splicing regulation on target exons. Obtaining a detailed atomic view hinges on determining a crystal structure of PTBP1 bound to a target RNA transcript. Here, we created a minimal functional PTBP1 with deletions in both linker 1 and linker 2 regions and assayed for activity on certain regulated exons, including the c-Src N1 exon. We show that for a subset of PTBP1-regulated exons the linker regions are not necessary for splicing repression activity. Gel mobility shift assays reveal the linker deletion mutant binds with 12-fold higher affinity to a target RNA sequence compared to wild-type PTBP1. A minimal PTBP1 that also contains an N-terminal region deletion binds to a target RNA with an affinity higher than that of wild-type PTBP1. Moreover, this minimal protein oligomerizes readily to form a distinct higher-order complex previously shown to be required for mediating splicing repression. This minimal functional PTBP1 protein can serve as a candidate for future structure studies to understand the mechanism of splicing repression for certain regulated exons.

Health Status of North Korean Refugees in Toronto: A Community Based Participatory Research Study.

Increasing numbers of North Koreans are fleeing their country due to economic insecurity and political persecution, with over 1000 North Koreans Refugee (NKR) claims in Canada in the past decade. There is little published on their health. Using a Community-Based Participatory Research (CBPR) methodology, we investigated NKR health status through a retrospective chart review of 1022 patients rostered at a Toronto refugee clinic between December 2011 and June 2014. The health status of 117 NKRs was compared to that of 905 other refugees seen during the same period. There were lower rates of chronic diseases, including obesity and elevated blood pressure, among NKRs. Conversely, some infectious diseases were more prevalent, including hepatitis B and chlamydia. Female NKRs had higher rates of abnormal cervical cytology. This study uniquely uses CBPR methodology to examine the health of NKRs, and can help guide targeted interventions in this population.

ROCK-isoform-specific polarization of macrophages associated with age-related macular degeneration.

Age is a major risk factor in age-related macular degeneration (AMD), but the underlying cause is unknown. We find increased Rho-associated kinase (ROCK) signaling and M2 characteristics in eyes of aged mice, revealing immune changes in aging. ROCK isoforms determine macrophage polarization into M1 and M2 subtypes. M2-like macrophages accumulated in AMD, but not in normal eyes, suggesting that these macrophages may be linked to macular degeneration. M2 macrophages injected into the mouse eye exacerbated choroidal neovascular lesions, while M1 macrophages ameliorated them, supporting a causal role for macrophage subtypes in AMD. Selective ROCK2 inhibition with a small molecule decreased M2-like macrophages and choroidal neovascularization. ROCK2 inhibition upregulated M1 markers without affecting macrophage recruitment, underlining the plasticity of these macrophages. These results reveal age-induced innate immune imbalance as underlying AMD pathogenesis. Targeting macrophage plasticity opens up new possibilities for more effective AMD treatment.