The role of frailty in geriatric cranial neurosurgery for primary central nervous system neoplasms

OBJECTIVE. Frailty is a clinical state of increased vulnerability due to age-associated decline and has been well established as a perioperative risk factor. Geriatric patients have a higher risk of frailty, higher incidence of brain cancer, and increased postoperative complication rates compared to nongeriatric patients. Yet, literature describing the effects of frailty on short- and long-term complications in geriatric patients is limited. In this study, the authors evaluate the effects of frailty in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. METHODS. The authors conducted a retrospective cohort study of geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm between 2010 and 2017 by using the Nationwide Readmission Database. Demographics and frailty were queried at primary admission, and readmissions were analyzed at 30-, 90-, and 180-day intervals. Complications of interest included infection, anemia, infarction, kidney injury, CSF leak, urinary tract infection, and mortality. Nearest-neighbor propensity score matching for demographics was implemented to identify nonfrail control patients with similar diagnoses and procedures. The analysis used Welch two-sample t-tests for continuous variables and chi-square test with odds ratios. RESULTS. A total of 6713 frail patients and 6629 nonfrail patients were identified at primary admission. At primary admission, frail geriatric patients undergoing cranial neurosurgery had increased odds of developing acute posthemorrhagic anemia (OR 1.56, 95% CI 1.23–1.98; p = 0.00020); acute infection (OR 3.16, 95% CI 1.70–6.36; p = 0.00022); acute kidney injury (OR 1.32, 95% CI 1.07–1.62; p = 0.0088); urinary tract infection prior to discharge (OR 1.97, 95% CI 1.71–2.29; p < 0.0001); acute postoperative cerebral infarction (OR 1.57, 95% CI 1.17–2.11; p = 0.0026); and mortality (OR 1.64, 95% CI 1.22–2.24; p = 0.0012) compared to nonfrail geriatric patients receiving the same procedure. In addition, frail patients had a significantly increased inpatient length of stay (p < 0.0001) and all-payer hospital cost (p < 0.0001) compared to nonfrail patients at the time of primary admission. However, no significant difference was found between frail and nonfrail patients with regard to rates of infection, thromboembolism, CSF leak, dural tear, cerebral infarction, acute kidney injury, and mortality at all readmission time points. CONCLUSIONS. Frailty may significantly increase the risks of short-term acute complications in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. Long-term analysis revealed no significant difference in complications between frail and nonfrail patients. Further research is warranted to understand the effects and timeline of frailty in geriatric patients

Preoperative Depression Screening in Primary Lumbar Fusion: An Evaluation of Its Modifiability on Outcomes in Patients with Diagnosed Depressive Disorder.

Studies have reported the detrimental effects of depression following spine surgery, however none have evaluated whether preoperative depression screening, in patients with a history of depression, is protective from adverse outcomes and lowers healthcare costs. We studied whether depression screenings/psychotherapy visits within 3 months prior to 1-2 level lumbar fusion (1-2LF) were associated with lower: 1) medical complications; 2) emergency department (ED) utilizations; 3) readmissions; and 4) healthcare costs.The PearlDiver database from 2010 to 2020 was queried for depressive disorder (DD) patients undergoing primary 1-2LF. Two cohorts were 1:5 ratio matched and included those with (n=2,622) or without (n=13,058) a pre-operative depression screen/psychotherapy visit within 3 months of LF. A 90-day surveillance period was utilized to compare outcomes. Logistic regression models computed odds ratios (OR) of complications and readmissions. P values less than 0.003 were significant.DD patients without depression screening had significantly greater incidence and odds of experiencing medical complications (40.57% vs. 16.00%; OR: 2.71,p<0.0001). Rates of ED utilization were increased in patients without screening vs. screening (15.78% vs 4.23%; OR: 4.25,p<0.0001), despite no difference in readmissions (9.31% vs 9.53%; OR: 0.97,p=0.721). Finally, 90-day reimbursements ($51,160 vs$54,731) were significantly lower in the screened cohort (all p<0.0001).Patients who underwent a pre-operative depression screening within 3 months of lumbar fusion had decreased medical complications, ED utilizations, and lower healthcare costs. Spine surgeons may use this data to counsel their patients with depression prior to surgical intervention.AMSUNY DownstateSurgeryN/

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

National Trends in Lumbar Degenerative Spondylolisthesis With Stenosis Treated With Fusion Versus Decompression

Objective The purpose of this study is to describe utilization, demographics, complications, and revisions for patients with degenerative spondylolisthesis (DS) with stenosis undergoing decompression or decompression with fusion in the United States. Methods A national insurance database was used to identify patients who underwent either decompression and fusion or decompression alone for management of DS from 2010–2022. Utilization trends, demographics, and complications for each procedure were compared. Results A total of 162,878 patients were identified, of which 78,043 patients underwent combined single-level lumbar decompression and fusion and 84,835 underwent single-level lumbar decompression alone. Between 2010–2021, lumbar decompression and fusion became the predominant surgical intervention for DS in 2016 and continued to account for more than half of all procedures during the remainder of the study period. Factors such as age, sex, comorbidities, geographic region, and physician specialty training were associated with procedure choice. Decompression with fusion was associated with a lower risk of revision surgery up to 5 years postoperatively and an overall lower incidence of 30-day complications. Conclusion Decompression with fusion has become the most common treatment for lumbar DS over the past decade despite a lack of compelling evidence supporting its use compared to decompression alone. A variety of patient and surgeon-specific factors is associated with procedure choice. After accounting for cofounders, we identified treatment-specific complications that may be valuable when counseling patients

Neoantigen-Specific Cytotoxic TR1 CD4 T Cells Suppress Cancer Immunotherapy

CD4+ T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses1-5, other CD4+ T cells have recently been implicated in inhibiting this response6,7. Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection. Characterization of the inhibitory cells induced by HDVax identified them as type 1 regulatory T (Tr1) cells expressing IL-10, granzyme B, perforin, CCL5 and LILRB4. Tumour-specific Tr1 cells suppressed tumour rejection induced by anti-PD1, LDVax or adoptively transferred tumour-specific effector T cells. Mechanistically, HDVax-induced Tr1 cells selectively killed MHC-II tumour antigen-presenting type 1 conventional dendritic cells (cDC1s), leading to low numbers of cDC1s in tumours. We then documented modalities to overcome this inhibition, specifically via anti-LILRB4 blockade, using a CD8-directed IL-2 mutein, or targeted loss of cDC2/monocytes. Collectively, these data show that cytotoxic Tr1 cells, which maintain peripheral tolerance, also inhibit antitumour responses and thereby function to impede immune control of cancer

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery