Cohort Of Patients Research Articles

Distribution of Major Histocompatibility Complex Alleles in Cohorts of Patients with Different Levels of Post-­Vaccination Antibodies against Hepatitis B

Relevance. It is known that the immune response to the administration of immunobiological drugs is variable and depends on the individual characteristics of the organism. Host immunogenetic factors have a significant impact on the effectiveness of vaccination. In this study, the frequencies of alleles of the HLA class I (HLA-A, B, C) and class II genes (HLA-DRB1, DPB1, DQB1) were studied in groups of participants with different levels of antibodies (anti-HBs) after vaccination against viral hepatitis B. Aims of the work was to determine the possible relationship between alleles of HLA genes and the intensity of post-vaccination immunity against hepatitis B. Materials and methods. The study included 271 apparently healthy adults who were divided into 3 groups depending on the specific concentration of post-vaccination antibodies (anti-HBs) using ELISA. All calculations were made relative to the groups anti-HBs >100 mIU/ml (n=82), 10-100 mIU/ml (n=98) (protective antibody level) and anti-HBs <10 mIU/ml (n = 91). To type alleles of the HLA class I (HLA-A, B, C) and class II (HLA-DRB1, DPB1, DQB1) genes, we used a panel we developed for whole-genome next-generation sequencing (NGS). Statistical analysis was performed using Pearson's χ2 goodness-of-fit test using the FDR multiple correction method with an initial target of p < 0.05. Results. When typing the six genes studied, the total number of alleles identified at least once was 189 variants that were distinct from each other. We identified 3 alleles (B*38:01:01, DQB1*06:03:01 and DRB1*13:01:01), which were significantly more common (FDR p < 0.05) in the group with a protective level of anti-HBsS. Also in this group there was an increased frequency of occurrence of alleles A*26:01:01, A*32:01:01, C*12:03:01, DPB1*04:01:01 and haplotypes DQB1*06:03:01 -DRB1*13:01:01 and B*38:01:01-C*12:03:01. In the group of seronegative patients, alleles A*02:01:01, A*03:01:01, B*44:02:01, B*44:27:01, C*07:04:01, DPB1*04 were more common :01:01, DQB1*05:01:01, DRB1*01:01:01 and DRB1*16:01:01. It was shown that the identified associations were more significant in the group of individuals with a concentration of post-vaccination anti-HBs above 100 mIU/ml. Conclusion. The results obtained indicate that the HLA alleles we identified may influence the level of anti-HBsS production, and that the genetic factor may, to a greater extent, determine whether the antibody level exceeds 100 mIU/ml. defined as an anti-HBS level of 10 mIU/ ml. The development of an integrated approach to the organization of vaccine prevention, including the determination of genetic markers, will improve the quality of immunization of the population. Information about the association of HLA gene alleles can be used to develop predictive scenarios for the development of the hepatitis B epidemic process.

Determination of NAT2 Genotypes in a Cohort of Patients with Suspected TB in the State of Rio de Janeiro

Determination of NAT2 Genotypes in a Cohort of Patients with Suspected TB in the State of Rio de Janeiro

Routine Coronary Angiography and Functional Cardiac Tests before Resection of Abdominal Aortic Aneurysm in Patients without Symptoms of Myocardial Infarction

INTRODUCTION: Cardiac complications are leaders in the structure of mortality of patients after resection of abdominal aortic aneurysms (AAA). In recent years more data have been obtained on the possibility of performing invasive coronary angiography (CAG) as a method of preoperative assessment of the condition of the coronary arteries. AIM: To assess the tactics of routine CAG and preventive revascularization of the myocardium in comparison with non-invasive functional tests in patients without clinical manifestations of coronary heart disease (CHD) from positions of the hospital outcomes of AAA resections. MATERIALS AND METHODS: A retrospective study included 205 patients without clinical and instrumental signs of CHD who underwent AAA resection at National Medical Research Center of Surgery named after A. Vishnevsky in 2001–2021. Patients of the first group (n = 55) underwent CAG before AAA resection and, if significant stenosis of coronary arteries was detected, revascularization of the myocardium was performed. In patients of the second group (n = 71), only functional cardiac tests were conducted before the operation. Patients of the third group were operated on without additional evaluation of cardiac status. RESULTS: In 30.9% of patients of the first group, significant coronary lesions were detected, in 29.5% of them with the involvement of the left main coronary artery. This required 10 percutaneous coronary interventions and 5 coronary artery bypass surgeries, which made 27.0% of patients in this group. No cases of myocardial infarction were recorded in this group. In the second and third groups, one case of myocardial infarction in each group was recorded (p = 0.688). There was no significant difference in the postoperative mortality in all the groups (1.8%; 4.2%; 2.5%, respectively; p = 0.704). To this end, maximally invasive diagnostic tactics increased the average waiting time for AAA resection: 52.2 ± 6.0 days in groups without coronary angiography and myocardial revascularization versus 99.2 ± 13.0 days in the first group. CONCLUSION: In a cohort of patients without anamnestic and clinical manifestations of coronary artery disease, the tactics of routine coronary angiography followed by prophylactic myocardial revascularization did not improve the short-term results of AAA resection, while the waiting period for intervention on the abdominal aorta increased. Preoperative tactics with functional cardiac tests also did not affect the treatment results.

Glycemic Risk Index in a Cohort of Patients with Type 1 Diabetes Mellitus Stratified by the Coefficient of Variation: A Real-Life Study.

Objective: To analyze the Glycemic Risk Index (GRI) and assess their possible differences according to coefficient of variation (CV) in a cohort of real-life type 1 diabetes mellitus (DM) patient users of intermittently scanned continuous glucose monitoring (isCGM). Patients and Methods: In total, 447 adult users of isCGM with an adherence ≥70% were included in a cross-sectional study. GRI was calculated with its hypoglycemia (CHypo) and hyperglycemia (CHyper) components. Multivariate linear regression analysis was performed to evaluate the factors associated with GRI. Results: Mean age was 44.6 years (standard deviation [SD] 13.7), 57.7% being male; age of DM onset was 24.5 years (SD 14.3) and time of evolution was 20.6 years (SD 12.3). In patients with CV >36% (52.8%) versus CV ≤36% (47.2%), differences were observed in relation to GRI (18.8% [SD 1.9]; P < 0.001), CHypo (2.9% [SD 0.3]; P < 0.001), CHyper (6.3% [SD 1.4]; P < 0.001), and all classical glucometric parameters except time above range level 1. The variables that were independently associated with GRI in patient with CV >36% were time in range (TIR) (β = -1.49; confidence interval [CI:] 95% -1.63 to -1.37; P < 0.001), glucose management indicator (GMI) (β = -7.22; CI: 95% -9.53 to -4.91; P < 0.001), and CV (β = 0.85; CI: 95% 0.69 to 1.02; P < 0.001). However, in patients with CV ≤36%, the variables were age (β = 0.15; CI: 95% 0.03 to 0.28; P = 0.019), age of onset (β = -0.15; CI: 95% -0.28 to -0.02; P = 0.023), TIR (β = -1.35; CI: 95% -1.46 to -1.23; P < 0.001), GMI (β = -6.67; CI: 95% -9.18 to -4.15; P < 0.001), and CV (β = 0.33; CI: 95% 0.11 to 0.56; P = 0.004). Conclusions: In this study, the factors independently associated with metabolic control according to GRI are modified by glycemic variability.

The efficacy of almonertinib and anlotinib combination therapy for advanced non-small-cell lung cancer patients who continued to experience cancer progression during third-generation EGFR-TKI treatment: a retrospective study.

Epidermal growth factor receptor (EGFR) mutations are key drivers in a significant portion of non-small-cell lung cancer (NSCLC) patients. While third-generation EGFR-tyrosine kinase inhibitors (TKIs) such as osimertinib have demonstrated efficacy, the management of patients who continue to experience disease progression during treatment remains challenging. The emergence of drug resistance, including the development of secondary mutations, necessitates exploration of alternative treatment strategies. This study aims to evaluate and observe the efficacy and safety of almonertinib combined with anlotinib in patients after cancer progression during third-generation EGFR-TKI therapy. In this retrospective analysis, we included EGFR-mutated NSCLC patients who were resistant to third-generation EGFR-TKIs. All patients were treated with almonertinib combined with anlotinib. The clinical characteristics, treatment history, clinical benefits, and adverse events of these patients were retrospectively collected. A total of 16 eligible patients were included in the analysis. The results revealed that combination therapy with almonertinib and anlotinib was effective in this patient cohort. The overall response rate was 25% and the disease control rate was 93.75%. The 6 and 12 months of PFS rates were 92.9% (95% confidence interval [CI] 80.3%, 100.0%) and 84.4% (95% CI 66.6%, 100.0%), respectively. Moreover, this combination therapy was generally well-tolerated, with manageable adverse events. Our retrospective analysis suggests that almonertinib and anlotinib combination therapy may represent a viable option for EGFR-mutated NSCLC patients who have progressed on third-generation EGFR-TKIs, especially for those with posterior lines and no standard treatment options. Further investigation and larger clinical trials are warranted to validate these observations and refine treatment guidelines.

Evaluating and Updating the IMPACT model to predict outcomes in two contemporary North American TBI cohorts.

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) model is a widely recognized prognostic model applied after traumatic brain injury (TBI). However, it was developed with patient cohorts that may not reflect modern practice patterns in North America. We analyzed data from two sources: the placebo arm of the phase II double-blind, multicenter randomized controlled trial Prehospital Tranexamic Acid for TBI (TXA) cohort and data from an observational cohort with similar inclusion/exclusion criteria (Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures (PROTIPS) cohort). All three versions of the IMPACT model - core, extended, and laboratory - were evaluated for 6-month mortality (GOSE=1) and unfavorable outcomes (GOSE=1-4). Calibration (intercept and slope) and discrimination (ROC-AUC) were used to assess model performance. We then compared three model updating methods - recalibration in the large, logistic recalibration, and coefficient update - with the best update method determined by likelihood ratio tests. In our calibration analysis, recalibration improved both intercepts and slopes, indicating more accurate predicted probabilities when recalibration was done. Discriminative performance of the IMPACT models, measured by AUC, showed mortality prediction ROCs between 0.61 to 0.82 for the TXA cohort, with the coefficient updated Lab model achieving the highest at 0.84. Unfavorable outcomes had lower AUCs, ranging from 0.60 to 0.79. Similarly, in the PROTIPS cohort, AUCs for mortality ranged from 0.75 to 0.82, with the coefficient updated Lab model also showing superior performance (AUC 0.84). Unfavorable outcomes in this cohort presented AUCs from 0.67 to 0.73, consistently lower than mortality predictions. The closed testing procedure using likelihood ratio tests consistently identified the coefficient update model as superior, outperforming the original and recalibrated models across all cohorts. In our comprehensive evaluation of the IMPACT model, the coefficient updated models were the best-performing across all cohorts through a structured closed testing procedure. Thus, standardization of model updating procedures is needed to reproducibly determine the best performing versions of IMPACT that reflect the specific characteristics of a dataset.

Evaluating and Updating the IMPACT model to predict outcomes in two contemporary North American TBI cohorts.

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) model is a widely recognized prognostic model applied after traumatic brain injury (TBI). However, it was developed with patient cohorts that may not reflect modern practice patterns in North America. We analyzed data from two sources: the placebo arm of the phase II double-blind, multicenter randomized controlled trial Prehospital Tranexamic Acid for TBI (TXA) cohort and data from an observational cohort with similar inclusion/exclusion criteria (Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures (PROTIPS) cohort). All three versions of the IMPACT model - core, extended, and laboratory - were evaluated for 6-month mortality (GOSE=1) and unfavorable outcomes (GOSE=1-4). Calibration (intercept and slope) and discrimination (ROC-AUC) were used to assess model performance. We then compared three model updating methods - recalibration in the large, logistic recalibration, and coefficient update - with the best update method determined by likelihood ratio tests. In our calibration analysis, recalibration improved both intercepts and slopes, indicating more accurate predicted probabilities when recalibration was done. Discriminative performance of the IMPACT models, measured by AUC, showed mortality prediction ROCs between 0.61 to 0.82 for the TXA cohort, with the coefficient updated Lab model achieving the highest at 0.84. Unfavorable outcomes had lower AUCs, ranging from 0.60 to 0.79. Similarly, in the PROTIPS cohort, AUCs for mortality ranged from 0.75 to 0.82, with the coefficient updated Lab model also showing superior performance (AUC 0.84). Unfavorable outcomes in this cohort presented AUCs from 0.67 to 0.73, consistently lower than mortality predictions. The closed testing procedure using likelihood ratio tests consistently identified the coefficient update model as superior, outperforming the original and recalibrated models across all cohorts. In our comprehensive evaluation of the IMPACT model, the coefficient updated models were the best-performing across all cohorts through a structured closed testing procedure. Thus, standardization of model updating procedures is needed to reproducibly determine the best performing versions of IMPACT that reflect the specific characteristics of a dataset.

Cardiovascular and All-Cause Mortality Is Affected by Serum Magnesium and Diet Pattern in a Cohort of Dialysis Patients

Background: Hypomagnesaemia is associated with an increased overall mortality in patients with chronic kidney disease on dialysis (CKD-5D). Mediterranean-style diet (MD), having a high magnesium content, can serve as a form of dietary magnesium supplementation. We examined whether there is a potential link between increased Mediterranean Diet score (MDS) and elevated serum magnesium (sMg) to assess its impact on reducing mortality risk in CKD-5D patients. Methods: In this multi-center prospective observational study, 117 CKD-5D patients (66 on hemodialysis and 51 on peritoneal dialysis) with a mean age of 62 ± 15 years were studied for a median follow-up period of 68 months. After baseline assessment, including measurement of sMg and MDS, all patients were followed up for cardiovascular (CV) and all-cause mortality. Results: Forty deaths occurred, 58% of which were cardiovascular. Patients who were above the median value of sMg (2.2 mg/dL) had a 66% reduction in CV (crude HR, 0.34; 95% CI, 0.11–0.70), and 49% reduction in all-cause (crude HR, 0.51; 95% CI, 0.27–0.96) mortality, even after adjustment for age, malnutrition inflammation score, left ventricular mass index, peripheral vascular disease and diabetes. Similar results were obtained when sMg was analyzed as a continuous variable. sMg was associated directly with MDS (r = 0.230; p = 0.012). Conclusions: Higher sMg levels are strongly and independently associated with reduced CV and all-cause mortality in CKD-5D patients. A strong correlation exists between MDS and sMg. Elevated sMg levels, achieved through MD adherence, can significantly reduce CV mortality, implicating MD as a mediator of the association between sMg and CV mortality.

Extended remdesivir administration in haematological patients with malignancies and COVID-19 during the Omicron era: safety and outcomes.

To describe the management of haematological patients experiencing prolonged SARS-CoV-2 viral shedding, as the optimal management strategy for this condition remains undetermined. We conducted a retrospective evaluation of our prospectively followed cohort of haematological patients treated with remdesivir for more than 10 days. Starting January 2023, upon COVID-19 diagnosis, the treatment strategy was based on symptoms and PCR cycle threshold (Ct) as follows: (i) when Ct was 25 or less or if the patient had symptoms, a course of remdesivir for at least 10 days, nirmatrelvir/ritonavir for 5 days (whenever possible) and convalescent plasma was administered; and (ii) when the patient was asymptomatic and had a PCR Ct of more than 25, when possible, a course of 5 days of nirmatrelvir/ritonavir was administered. The patient was considered to have achieved viral clearance and, thus, remdesivir was stopped, in either of these cases: (i) PCR negativity, or (ii) subgenomic RNA negativity. From January to November 2023, 18 patients benefited from a safe extended remdesivir administration, resulting in detection of SARS-CoV-2 viral clearance in a median time of 3.5 weeks (IQR 2.6-3.9) (min-max 1.6-8.0). No clinical or biological side effects were detected. No patient died or needed further treatment for their COVID-19 episode. The extended course of remdesivir, combined with other active therapies for COVID-19 infection, was well tolerated. Cure and virus negativity were obtained in all these high-risk patients.

The Association of Surgical Setting With Opioid Prescribing Patterns Following Wide-Awake Trigger Finger Release.

Wide-awake and office-based hand surgeries are increasingly common. The association of these techniques with postoperative pain and pain control has garnered recent attention. A prior study demonstrated that office-based trigger finger release (TFR) were associated with decreased perioperative opioid prescriptions compared to those performed in the operating room. The current study provides an in-depth analysis of the association between surgical setting and perioperative opioid prescriptions for wide-awake TFR. Patients undergoing TFR between 2010 and 2021 were identified in PearlDiver, a national administrative claims database. Exclusion criteria were age <18 years, <6 months of preoperative data, <1 month of postoperative data, bilateral TFR, and concomitant hand surgery. To identify wide-awake cases, patients with procedural codes for general anesthesia, monitored anesthesia care, sedation and regional blocks were excluded. Patients were stratified by surgical setting (office or operating room), then matched based on age, sex, Elixhauser Comorbidity Index score, and geographic region. Patients with prior opioid prescriptions, opioid dependence, opioid abuse, substance use disorder, chronic back/neck pain, generalized anxiety, and major depression were identified. Perioperative opioid prescriptions (those filled within 7 days before or 30 days after surgery) were characterized. There were 16,604 matched wide-awake TFR patients in each cohort. In the cohort of office-based patients, 4,993 (30%) filled a prescription for perioperative opioids, in contrast to 8,763 (53%) patients who underwent surgery in the operating room. This disparity was statistically significant in both univariate and multivariate analyses. Univariate analysis indicated that office-based surgeries were linked to lower morphine milligram equivalents (MME) in opioid prescriptions than those performed in operating rooms (median of 140 vs 150, respectively). However, multivariate analysis demonstrated that opioid prescriptions for office-based surgeries were actually associated with greater MME. Patients undergoing office-based TFR were less likely to fill perioperative opioid prescriptions but were prescribed opioids with greater MME. In wide-awake TFR, it appears that a disparity may exist in patient and provider beliefs about postoperative pain control. Future patient- and provider-level investigations may produce insights into perceptions of postoperative pain and pain control, which may be useful for reducing opioid prescriptions across surgical settings.

Combined detection of serum EFNA1 and MMP13 as diagnostic biomarker for gastric cancer

We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC.

Combined detection of serum EFNA1 and MMP13 as diagnostic biomarker for gastric cancer

We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC.

Transfers from home to facility-based dialysis: Comparisons of HHD, assisted PD and autonomous PD

Abstract Background Home dialysis therapies such as peritoneal dialysis (PD) and home hemodialysis (HHD) are beneficial for quality of life and patient empowerment. The short technique survival time partly explains their low prevalence. We aimed to assess the risk of transfer to facility-based hemodialysis in patients treated with autonomous PD, assisted PD and HHD. Methods This was a retrospective study using data from the REIN registry of patients starting home dialysis in France from 2002 to 2019. The risks of transfer to facility-based hemodialysis (HD) were compared between three modalities of home dialysis (HHD, nurse-assisted PD, autonomous PD) using survival models with a propensity score (PS)-matched and unmatched cohort of patients. Results The study included 17 909 patients: 628 in the HHD group, 10 214 in the autonomous PD group and 7067 in the assisted PD group. During the follow-up period, there were 5347 transfers to facility-based HD. The observed number of transfers was 2458 (13.7%) at one year and 5069 (28.3) at five years after the start of home dialysis, including 3272 (32%) on autonomous PD, 1648 (23.3%) on assisted PD, and 149 (23.7) on HHD. Due to clinical characteristics differences, only 38% of HHD patients could be matched to patients from the others group. In the PS-matched cohort, the adjusted Cox model showed no difference in the risk of transfer for assisted PD (cs-HR 1.04, 95% CI 0.75–1.44) or HHD (cs-HR 1.07, 95% CI 0.77–1.48) compared with autonomous PD. Conclusions Unlike results from other countries, where nurse assistance is not fully available for PD-associated care, there was no difference in technique survival between autonomous PD, nurse-assisted PD, and HHD in France. This discrepancy may be attributed to our inclusion of a broader spectrum of patients who derive significant benefits from assisted PD.

Eligibility for vericiguat in a real-world, contemporary heart failure population.

Vericiguat is a soluble guanylate cyclase stimulator and improves survival in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and an increased risk of decompensation. As real-world data on how many patients could be eligible for vericiguat therapy derive from outdated registries, we aimed to assess eligibility in a prospective cohort of patients with HF. Data from consecutive HF patients undergoing an elective ambulatory visit at five university hospitals from 3 July to 28 July 2023 were collected. Independent investigators assessed which patients (i) met the eligibility criteria of the VICTORIA trial, (ii) complied with HF guideline recommendations, (iii) met regulatory agency criteria, or (iv) met criteria for refundability according to the Italian regulatory agency. Patients (n=346, 72% men, median age 69years) had HFrEF in 57% of cases, left ventricular ejection fraction<45% in 68%, and New York Heart Association class II-IV symptoms in 76%. Patients meeting the eligibility criteria of the VICTORIA trial or European and American HF Guideline recommendations were 9% and 13%, respectively. Patients meeting Food and Drug Administration (FDA) or European Medicines Agency (EMA) label criteria were 19% and 17%, respectively. Drug costs would be covered by the Italian National Health System in 10% of patients [if a sodium-glucose cotransporter-2 inhibitor (SGLT2i) is not mandatory] or in 8% (if an SGLT2i is requested). In a real-world study, 9% of patients met the eligibility criteria of the VICTORIA trial, but up to 13% complied with guideline recommendations and up to 19% met FDA or EMA criteria. In Italy, drug costs would be covered by up to 10% of patients.

CSF formation rate—a potential glymphatic flow parameter in hydrocephalus?

BackgroundStudies indicate that brain clearance via the glymphatic system is impaired in idiopathic normal pressure hydrocephalus (INPH). This has been suggested to result from reduced cerebrospinal fluid (CSF) turnover, which could be caused by a reduced CSF formation rate. The aim of this study was to determine the formation rate of CSF in a cohort of patients investigated for INPH and compare this to a historical control cohort.MethodsCSF formation rate was estimated in 135 (75 ± 6 years old, 64/71 men/women) patients undergoing investigation for INPH. A semiautomatic CSF infusion investigation (via lumbar puncture) was performed. CSF formation rate was assessed by downregulating and steadily maintaining CSF pressure at a zero level. During the last 10 min, the required outflow to maintain zero pressure, i.e., CSF formation rate, was continuously measured. The values were compared to those of a historical reference cohort from a study by Ekstedt in 1978.ResultsMean CSF formation rate was 0.45 ± 0.15 ml/min (N = 135), equivalent to 27 ± 9 ml/hour. There was no difference in the mean (p = 0.362) or variance (p = 0.498) of CSF formation rate between the subjects that were diagnosed as INPH (N = 86) and those who were not (N = 43). The CSF formation rate in INPH was statistically higher than in the reference cohort (0.46 ± 0.15 vs. 0.40 ± 0.08 ml/min, p = 0.005), but the small difference was probably not physiologically relevant. There was no correlation between CSF formation rate and baseline CSF pressure (r = 0.136, p = 0.115, N = 135) or age (-0.02, p = 0.803, N = 135).ConclusionsThe average CSF formation rate in INPH was not decreased compared to the healthy reference cohort, which does not support reduced CSF turnover. This emphasizes the need to further investigate the source and routes of the flow in the glymphatic system and the cause of the suggested impaired glymphatic clearance in INPH.

Higher levels of IL-1ra, IL-6, IL-8, MCP-1, MIP-3α, MIP-3β, and fractalkine are associated with 90-day mortality in 132 non-immunomodulated hospitalized patients with COVID-19.

Immune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy. Levels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation. A total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3β, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes. We showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.

Investigating the Determinants of Mortality before CD4 Count Recovery in a Cohort of Patients Initiated on Antiretroviral Therapy in South Africa Using a Fine and Gray Competing Risks Model

Investigating the Determinants of Mortality before CD4 Count Recovery in a Cohort of Patients Initiated on Antiretroviral Therapy in South Africa Using a Fine and Gray Competing Risks Model

Investigating the Determinants of Mortality before CD4 Count Recovery in a Cohort of Patients Initiated on Antiretroviral Therapy in South Africa Using a Fine and Gray Competing Risks Model

CD4 count recovery is the main goal for an HIV patient who initiated ART. Early ART initiation in HIV patients can help restore immune function more effectively, even when they have reached an advanced stage. Some patients may respond positively to ART and attain CD4 count recovery. Meanwhile, other patients failing to recover their CD4 count due to non-adherence, treatment resistance and virological failure might lead to HIV-related complications and death. The purpose of this study was to find the determinants of death in patients who failed to recover their CD4 count after initiating antiretroviral therapy. The data used in this study was obtained from KwaZulu-Natal, South Africa, where 2528 HIV-infected patients with a baseline CD4 count of &lt;200 cells/mm3 were initiated on ART. We used a Fine–Gray sub-distribution hazard and cumulative incidence function to estimate potential confounding factors of death, where CD4 count recovery was a competing event for failure due to death. Patients who had no tuberculosis were 1.33 times at risk of dying before attaining CD4 count recovery [aSHR 1.33; 95% CI (0.96–1.85)] compared to those who had tuberculosis. Rural patients had a higher risk of not recovering and leading to death [aSHR 1.97; 95% CI (1.57–2.47)] than those from urban areas. The patient’s tuberculosis status, viral load, regimen, baseline CD4 count, and location were significant contributors to death before CD4 count recovery. Intervention programs targeting HIV testing in rural areas for early ART initiation and promoting treatment adherence are recommended.

MRI evaluation of ATFL and CFL ligamentization after anatomical surgical reconstruction with a hamstring graft

BackgroundChronic ankle instability is frequent complication following ankle sprains. Anatomical reconstruction of the anterior talofibular ligament (ATFL) and the calcaneofibular ligament (CFL) with a gracilis autograft is a validated reconstruction technique. The signal-to-noise quotient ankle (SNQA) score evaluates graft maturation with MRI and has been shown to be reproducible and reliable. The goal of this study was to evaluate the process of ligamentization of the anatomical reconstruction of the ankle using the SNQA. The hypothesis was that the SNQA signal of the ATFL and the CFL would decrease over time. MethodsA prospective cohort of patients who underwent arthroscopic anatomical ATFL-CFL reconstruction was included. All patients underwent a follow-up MRI examination 3, 6. and 12 months after surgery and the SNQA score was determined. ResultsTwenty consecutive patients were included. The SNQA score decreased significantly over time for the ATFL (p= 0.001), the CFL (p<0.001) and for the fibular bone tunnel-graft interface (p=0.02). The SNQA scores of the ATFL were significantly higher than those of the CFL at 3 months (p=0.01), 6 months (p=0.003) and 12 months (p<0.001), and then those of the fibular tunnel-graft interface at 12 months (p=0.003). There was no difference in the SNQA score between the CFL and in the fibular graft-bone tunnel interface at any of the follow up periods. ConclusionThere is a process of graft maturation following anatomical ATFL and CFL reconstruction over time, which is faster for the CFL than for the ATFL during the first year. Level of evidenceII

Transperineal laser ablation (TPLA) of the prostate for benign prostatic obstruction: the first 100 patients cohort of a prospective, single-center study

PurposeTransperineal laser ablation (TPLA) is a new minimally-invasive surgical treatment for patients with benign prostatic obstruction (BPO). We report the perioperative and mid-term functional results of the first 100 consecutively patients undergoing TPLA at our institution.MethodsClinical data from consecutive patients undergoing TPLA at our institution from April 2021 to July 2023 were prospectively collected. Primary endpoints were the postoperative changes in IPSS, QoL and MSHQ 3-item questionnaires and in Qmax and post-void residual volume (PVR).ResultsOverall, 100 consecutive patients underwent the procedure. Median age and prostate volume were 66 (IQR 60–75) years and 50 (IQR 40–70) ml, respectively. In the cohort, 14 (14%) patients had an indwelling catheter and 81 (81%) were under oral BPO therapy at the time of TPLA. Baseline median Qmax (ml/s) and PVR (ml) were 9.1 (IQR 6.9–12) and 90 (IQR 50–150), respectively, while median IPSS and QoL were 18 (IQR 15–23) and 4 (IQR 3–4). At all the follow-up timepoints, the evaluated outcomes on both symptoms and functional parameters showed a statistically significant improvement (p < 0.001). Antegrade ejaculation was preserved in all sexually active patients. No postoperative Clavien-Dindo > 2 complications were recorded.ConclusionsTPLA represents a safe option for selected well-informed patients swith LUTS due to BPO. Our prospective study confirms the feasibility and favorable perioperative and functional outcomes in a real-world cohort with heterogenous prostate volumes and patient characteristics.