Impaired Clinical Status Research Articles

Vitamin B12 status in hospitalised cancer patients: Prevalence and clinical implications of depletion and hypervitaminosis

Background & AimsThe prevalence and clinical significance of vitamin B12 alterations in patients with cancer are poorly understood. We aimed to assess the prevalence and risk factors of vitamin B12 depletion or hypervitaminosis in patients with cancer. Methods: We retrospectively included hospitalised patients with cancer in 2017-2022. Plasma B12 levels were stratified as very low (VL, <200 pg/ml), low (L, 200-299 pg/ml), normal (N, 300-812 pg/ml), or high (H, ≥813 pg/ml). We collected demographic and several clinical data (e.g., comorbidities, nutritional status, ECOG-PS, cancer site and stage). Univariate and multivariate analyses for factors associated to the vitamin B12 status were fitted. Results: 788 patients (F/M ratio 1.05, median age 72 years, [25th, 75th percentiles 62, 78 years]) were included. Vitamin B12 was VL in 14.1%, L in 19.4%, N in 49.4%, and H in 17.1% cases. Vitamin B12 distribution increased significantly as function of ECOG-PS levels. Patients with breast cancer were characterized by the highest median B12 value, while colorectal cancer patients by the lowest. Vitamin B12 was also significantly higher in advanced compared to early-stage patients as well as in those who had liver failure. Multivariate analysis showed that the probability of H vs. VL B12 levels was significantly increased in patients with hypoproteinemia, hypo-prealbuminemia, and ECOG-PS≥2, and decreased in those with colorectal and gastric cancer. Conclusion: Vitamin B12 impairment is common in cancer patients. Increased vitamin B12 is associated with an impaired clinical status, while vitamin B12 depletion is more common in early-stage cancer and in elderly patients.

Incidence and Predictors of Infections and All-Cause Death in Patients with Cardiac Implantable Electronic Devices: The Italian Nationwide RI-AIAC Registry.

Background: The incidence of infections associated with cardiac implantable electronic devices (CIEDs) and patient outcomes are not fully known. Aim: To provide a contemporary assessment of the risk of CIEDs infection and associated clinical outcomes. Methods: In Italy, 18 centres enrolled all consecutive patients undergoing a CIED procedure and entered a 12-months follow-up. CIED infections, as well as a composite clinical event of infection or all-cause death were recorded. Results: A total of 2675 patients (64.3% male, age 78 (70–84)) were enrolled. During follow up 28 (1.1%) CIED infections and 132 (5%) deaths, with 152 (5.7%) composite clinical events were observed. At a multivariate analysis, the type of procedure (revision/upgrading/reimplantation) (OR: 4.08, 95% CI: 1.38–12.08) and diabetes (OR: 2.22, 95% CI: 1.02–4.84) were found as main clinical factors associated to CIED infection. Both the PADIT score and the RI-AIAC Infection score were significantly associated with CIED infections, with the RI-AIAC infection score showing the strongest association (OR: 2.38, 95% CI: 1.60–3.55 for each point), with a c-index = 0.64 (0.52–0.75), p = 0.015. Regarding the occurrence of composite clinical events, the Kolek score, the Shariff score and the RI-AIAC Event score all predicted the outcome, with an AUC for the RI-AIAC Event score equal to 0.67 (0.63−0.71) p < 0.001. Conclusions: In this Italian nationwide cohort of patients, while the incidence of CIED infections was substantially low, the rate of the composite clinical outcome of infection or all-cause death was quite high and associated with several clinical factors depicting a more impaired clinical status.

Analysis of Risk Factors for Perioperative Acute Kidney Injury and Management Strategies.

Acute kidney injury (AKI) is a serious clinical syndrome, and one of the common comorbidities in the perioperative period. AKI can lead to complications in surgical patients and is receiving increasing attention in clinical workup. In recent years, the analysis of perioperative risk factors has become more in-depth and detailed. In this review, the definition, diagnosis, and pathophysiological characteristics of perioperative AKI are reviewed, and the main risk factors for perioperative AKI are analyzed, including advanced age, gender, certain underlying diseases, impaired clinical status such as preoperative creatinine levels, and drugs that may impair renal function such as non-steroidal anti-inflammatory drugs (NASIDs), ACEI/ARB, and some antibiotics. Injectable contrast agents, some anesthetic drugs, specific surgical interventions, anemia, blood transfusions, hyperglycemia, and malnutrition are also highlighted. We also propose potential preventive and curative measures, including the inclusion of renal risk confirmation in the preoperative assessment, minimization of intraoperative renal toxin exposure, intraoperative management and hemodynamic optimization, remote ischemic preadaptation, glycemic control, and nutritional support. Among the management measures, we emphasize the need for careful perioperative clinical examination, timely detection and management of AKI complications, administration of dexmedetomidine for renal protection, and renal replacement therapy. We aim that this review can further increase clinicians' attention to perioperative AKI, early assessment and intervention to try to reduce the risk of AKI.

Development and validation of a predictive model to determine the level of care in patients confirmed with COVID-19

Background The COVID-19 pandemic has imposed significant challenges on hospital capacity. While mitigating unnecessary crowding in hospitals is favourable to reduce viral transmission, it is more important to prevent readmissions with impaired clinical status due to initially inappropriate level of care. A validated predictive tool to assist clinical decisions for patient triage and facilitate remote stratification is of critical importance. Methods We conducted a retrospective study in patients with confirmed COVID-19 stratified into two levels of care, namely ambulatory care and hospitalization. Data on socio-demographics, clinical symptoms, and comorbidities were collected during the first (N = 571) and second waves (N = 174) of the pandemic in Belgium (2 March to 6 December 2020). Univariate and multivariate logistic regressions were performed to build and validate the prediction model. Results Significant predictors of hospitalization were old age (OR = 1.08, 95%CI:1.06–1.10), male gender (OR = 4.41, 95%CI: 2.58–7.52), dyspnoea (OR 6.11, 95%CI: 3.58–10.45), dry cough (OR 2.89, 95%CI: 1.54–5.41), wet cough (OR 4.62, 95%CI: 1.93–11.06), hypertension (OR 2.20, 95%CI: 1.17–4.16) and renal failure (OR 5.39, 95%CI: 1.00–29.00). Rhinorrhea (OR 0.43, 95%CI: 0.24–0.79) and headache (OR 0.36, 95%CI: 0.20–0.65) were negatively associated with hospitalization. A receiver operating characteristic (ROC) curve was constructed and the area under the ROC curve was 0.931 (95% CI: 0.910–0.953) for the prediction model (first wave) and 0.895 (95% CI: 0.833–0.957) for the validated dataset (second wave). Conclusion With a good discriminating power, the prediction model might identify patients who require ambulatory care or hospitalization and support clinical decisions by Emergency Department staff and general practitioners.

Frequent Use of Organs after Rescue Allocation for Heart Transplantation: Can We Still Achieve Adequate Results?

Purpose The number of patients on the heart waiting list in the ET-region is almost threefold higher than the number of patients who will actually undergo heart transplantation (htx). Consequently waiting times continue to increase and can be beyond a year even for high-urgent (HU)-listed patients. One possible solution for an increased donor pool is the acceptance of so-called marginal organs. This analysis deals with the effect of frequently using organs after rescue allocation for cardiac transplant in our department. Methods Between 10/2010 and 9/2018 115 patients underwent htx in our department. 65 of the 115 transplant recipients (56.5 %) were transplanted with HU-allocations (group HU), the remaining patients received organs after rescue allocation (gr. T). These organs had been rejected by at least 3 consecutive transplant centers due to medical reasons. Perioperative parameters of donor and recipient and posttransplant outcomes were compared between these 2 groups. Results Mean donor age was higher in group T (p 0.05). All other donor parameters (CMV status, time of ischemia as well as sex) were comparable between the groups. 30-day mortality was higher in HU-patients (12.3 %) compared to 10 % after rescue allocation, p>0.05. Primary graft dysfunction (PGD) with extracorporeal life support occurred in 33.8 % after HU-transplantation and in 18 % of gr. T (p 0.05). Conclusion Our data support the use of hearts after rescue allocation. Probably as a consequence of the impaired clinical status of HU-recipients, early mortality was lower in patients after receiving rescue organs. However, one-year survival was comparable again, indicating a yet remarkable mortality in those patients beyond the first postoperative month.

Cluster analysis identifying patients with COPD at high risk of 2-year all-cause mortality

The objective of the article is to identify clusters of patients with COPD according to factors known to be associated with mortality and to verify whether clusters’ assignment is associated with 2-year mortality. Patients (n = 141) were evaluated by bioelectrical impedance, maximal inspiratory pressure (MIP), one-repetition maximum test of the quadriceps femoris (1RMQF) and BODE index (body mass index; airflow obstruction (spirometry); dyspnea (modified Medical Research Council scale); and exercise capacity (6-minute walk test (6MWT) distance). Vital status was retrospectively checked 2 years after the assessments, and time to death was quantified for those deceased in this period. K-means analysis identified two clusters. Patients in cluster one (CL I, n = 69) presented an impaired clinical status in comparison to cluster two (CL II, n = 72). Receiver operating characteristics curves identified the cutoffs discriminating patients composing CL I: forced expiratory volume in the first second <44%pred; 6MWT <479 m; 1RMQF <19 kg; and maximum inspiratory pressures <73 cmH2O (area under the curve range 0.750–0.857). During the follow-up, 19 (13%) patients deceased, 15 in CL I (22%) and 4 in CL II (0.06%) (p = 0.005). CL I was associated with a higher risk of 2-year mortality (hazard ratio (95% confidence interval): 4.3 (1.40–12.9), p = 0.01). A cluster of patients with COPD highly associated with 2-year mortality was statistically identified, and cutoffs to identify these subjects were provided.

Mortality trends and risk factors in advanced stage-2 Human African Trypanosomiasis: A critical appraisal of 23 years of experience in the Democratic Republic of Congo.

We conducted a retrospective study on mortality trends and risk factors in 781 naïve cases of advanced stage-2 sleeping sickness admitted between 1989 and 2012 at the National Reference Center for Human African Trypanosomiasis (HAT), Department of Neurology, Kinshasa University, Democratic Republic of Congo (DRC). Death was the outcome variable whereas age, gender, duration of disease, location of trypanosomes in body fluids, cytorachy, protidorachy, clinical status (assessed on a syndromic and functional basis) on admission, and treatment regimen were predictors in logistic regression models run at the 0.05 significance level. Death proportions were 17.2% in the standard melarsoprol schedule (3-series of intravenous melarsoprol on 3 successive days at 3.6 mg/kg/d, with a one-week interval between the series, ARS 9); 12.1% in the short schedule melarsoprol (10 consecutive days of intravenous melarsoprol at 2.2 mg/kg/d, ARS 10), 5.4% in the first-line eflornithine (14 days of eflornithine at 400 mg/kg/d in 4 infusions a day DFMO B), 9.1% in the NECT treatment regimen (eflornithine for 7 days at 400, mg/kg/d in 2 infusions a day combined with oral nifurtimox for 10 days at 15 mg/kg/d in 3 doses a day); and high (36%) in the group with select severely affected patients given eflornithine because of their clinical status on admission, at the time when this expensive drug was kept for treatment of relapses (14 days at 400 mg/kg/d in 4 infusions a day, DFMO A). After adjusting for treatment, death odds ratios were as follows: 10.40 [(95% CI: 6.55–16.51); p = .000] for clinical dysfunction (severely impaired clinical status) on admission, 2.14 [(95% CI: 1.35–3.39); p = .001] for high protidorachy, 1.99 [(95% CI: 1.18–3.37); p = .010] for the presence of parasites in the CSF and 1.70 [(95% CI: 1.03–2.81); p = .038] for high cytorachy. A multivariable analysis within treatment groups retained clinical status on admission (in ARS 9, ARS 10 and DFMO B groups) and high protidorachy (in ARS 10 and DFMO B groups) as significant predictors of death. The algorithm for initial clinical status assessment used in the present study may serve as the basis for further development of standardized assessment tools relevant to the clinical management of HAT and information exchange in epidemiological reports.

Combined stereotactic biopsy and stepping-source interstitial irradiation of glioblastoma multiforme.

Patients diagnosed with glioblastoma multiforme receiving stereotactic biopsy only either due to tumor localization or impaired clinical status face a devastating prognosis with very short survival times. One strategy to provide an initial cytoreductive and palliative therapy at the time of the stereotactic biopsy is interstitial irradiation through the pre-defined trajectory of the biopsy channel. We designed a novel treatment planning system and evaluated the treatment potential of a fixed-source and a stepping-source algorithm for interstitial radiosurgery on non-spherical glioblastoma in direct adjacency to risk structures. Using both setups, we show that radiation doses delivered to 100% of the gross tumor volume shifts from sub-therapeutic (10-12 Gy) to sterilizing single doses (25-30 Gy) when using the stepping source algorithm due to improved sparing of organs-at-risk. Specifically, the maximum doses at the brain stem were 100% of the PTV dose when a fixed central source and 38% when a stepping-source algorithm was used. We also demonstrated precision of intracranial target points and stability of superficial and deep trajectories using both a phantom and a body donor study. Our setup now for the first time provides a basis for a clinical proof-of-concept trial and may widen palliation options for patients with limited life expectancy that should not undergo time-consuming therapies.

Adverse neuro-immune–endocrine interactions in patients with active tuberculosis

The nervous, endocrine and immune systems play a crucial role in maintaining homeostasis and interact with each other for a successful defensive strategy against injurious agents. However, the situation is different in long-term diseases with marked inflammation, in which defensive mechanisms become altered. In the case of tuberculosis (TB), this is highlighted by several facts: an imbalance of plasma immune and endocrine mediators, that results in an adverse environment for mounting an adequate response against mycobacteria and controlling inflammation; the demonstration that dehidroepiandrosterone (DHEA) secretion by a human adrenal cell line can be inhibited by culture supernatants from Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells - PBMC - of TB patients, with this effect being partly reverted when neutralizing transforming growth factor-β in such supernantants; the in vitro effects of adrenal steroids on the specific immune response of PBMC from TB patients, that is a cortisol inhibition of mycobacterial antigen-driven lymphoproliferation and interferon-γ production as well as a suppression of TGF-β production in DHEA-treated PBMC; and lastly the demonstration that immune and endocrine compounds participating in the regulation of energy sources and immune activity correlated with the consumption state of TB patients. Collectively, immune-endocrine disturbances of TB patients are involved in critical components of disease pathology with implications in the impaired clinical status and unfavorable disease outcome. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'.

Change over time of mortality predictors after HAART initiation in a Senegalese cohort

In 1998, Senegal was among the first sub-Saharan African countries to launch a Highly active anti-retroviral therapy (HAART) access program. Initial studies have demonstrated the feasibility and efficacy of this initiative. Analyses showed a peak of mortality short after starting HAART warranting an investigation of early and late mortality predictors. 404 HIV-1-infected Senegalese adult patients were enrolled and data censored as of September 2005. Predictor effects on mortality were first examined over the whole follow-up period (median 46 months) using a Cox model and Shoenfeld residuals. Then, changes of these effects were examined separately over the early and late treatment periods; i.e., less and more than 6-month follow-up. During the early period, baseline body mass index and baseline total lymphocyte count were significant predictors of mortality (Hazard Ratios 0.82 [0.72-0.93] and 0.80 [0.69-0.92] per 200 cell/mm3, respectively) while baseline viral load was not significantly associated with mortality. During the late period, viro-immunological markers (baseline CD4-cell count and 6-month viral load) had the highest impact. In addition, the viral load at 6-month was a significant predictor (HR = 1.42 [1.20-1.66]). In this cohort, impaired clinical status could explain the high early mortality rate while viro-immunological markers were rather predictors of late mortality.

Ventricular size and function assessed by cardiac MRI predict major adverse clinical outcomes late after tetralogy of Fallot repair

Background:Factors associated with impaired clinical status in a cross-sectional study of patients with repaired tetralogy of Fallot (TOF) have been reported previously.Objectives:To determine independent predictors of major adverse clinical outcomes...

ICAM-1, ICAM-2 and ICAM-3 in the Sera of Patients with Idiopathic Pulmonary Fibrosis

In order to test the serum levels of ICAM-1, ICAM-2 and ICAM-3 in patients with idiopathic pulmonary fibrosis (IPF), twenty patients with IPF and eleven with secondary interstitial fibrosis (SIF), as well as forty healthy volunteers (HV) were studied. Serum intracellular adhesion molecules (ICAM) 1, 2 and 3 were assessed by ELISA. Functional respiratory tests, which included spirometry and lung diffusing capacity were simultaneously performed. Median values of serum ICAM-1 and ICAM-2 were higher in the patients' than in the healthy volunteers' (HV) group: IPF group: 946.60 ng/ml and 400.14 ng/ml; SIF group: 901.58 ng/ml and 378.27 ng/ml; HV group: 308.40 ng/ml and 217.55 ng/ml, respectively (p<0.05). ICAM-3 serum levels were equal between the three groups. ICAM-2 negatively correlated to DLCO values. (p<0.005). It can be concluded that ICAM 1 and 2 are elevated in the sera of patients with pulmonary fibrosis. ICAM-2 might be associated with a more impaired clinical status.

Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging

ObjectivesThe purpose of this study was to identify independent factors associated with impaired clinical status in late survivors of tetralogy of Fallot (TOF) repair. BackgroundRepair of TOF often results in chronic pulmonary regurgitation (PR) and right ventricular (RV) dilation, which have been linked to late morbidity and mortality. However, determinants of clinical status late after TOF repair have not been fully characterized. MethodsThe clinical and laboratory data of 100 consecutive patients with repaired TOF (median 21 years after repair) who completed a cardiac magnetic resonance imaging protocol were analyzed. Impaired clinical status was defined as New York Heart Association (NYHA) functional class ≥III. ResultsOf the patients, 88 were in NYHA functional class I or II and 12 were in NYHA functional class III. The degree of PR and indexed RV end-diastolic volume were not associated with impaired clinical status. By multivariate analysis, a lower left ventricular (LV) ejection fraction (EF) (odds ratio [OR] = 3.88 for 10% decrease, p = 0.002) and older age at TOF repair (OR = 1.70 for 5-year increase, p = 0.013) were the strongest independent factors associated with impaired clinical status. Among RV variables, a lower RV EF was the strongest independent factors associated with poor clinical status (OR = 2.41 for 10% decrease, p = 0.01). The LV EF correlated with RV EF (r = 0.58, p < 0.001). ConclusionsModerate or severe LV or RV systolic dysfunction, but not PR fraction or RV diastolic dimensions, is independently associated with impaired clinical status in long-term survivors of TOF repair. The close relationship between LV EF and RV EF suggests unfavorable ventricular-ventricular interaction.