Correlation Between Tumor Response and Survival Outcomes in Patients with Advanced Gastric Cancer Receiving Ramucirumab and Paclitaxel as Second-Line Therapy.

BACKGROUND: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. The first-line treatment for GC is a combination of platinum and fluoropyrimidine-based therapy. Based on the positive results of RAINBOW and REGARD trials, ramucirumab either alone or in combination with paclitaxel has proved to be a safe and active option for second-line treatment in GC patients. MATERIAL AND METHODS: Advanced GC patients who received a 28-day cycles of ramucirumab and paclitaxel until disease progression or unacceptable toxicity were evaluated. Eligible patients had ECOG PS ≤ 1 and adequate organ function. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and Cox proportional-hazards regression models were used for survival analyses. RESULTS: In our single institution experience, we included a total of 67 patients. A median OS of 8 months and a median PFS of 4 months, were recorded. In patients experiencing an initial partial response (PR), we observed a significant association between tumor response and survival outcomes (OS and PFS). The OS and PFS were 15 and 11 months in patients who experienced PR compared to 8 and 4 months in patients without PR (p = 0.02; p = 0.04). CONCLUSION: Treatment with ramucirumab plus paclitaxel yielded the highest overall response rate reported to date for patients with previously treated advanced GC. In our experience, the initial tumor response is associated with a greater survival benefit which could be further improved by the identification of biomarkers predicting response.

State Agencies' Perspectives on Planning and Preparing for WIC Online Ordering Implementation.

Online ordering for the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) has the potential to alleviate some of the barriers faced by WIC participants when shopping with their WIC food benefits. WIC State agencies are the leaders in planning, preparing, implementing, maintaining, and expanding WIC online ordering. Cross-sectional web-based survey research was utilized to identify barriers to implementing WIC online ordering, as well as the support needed to overcome those barriers, from a WIC State agency perspective. Web surveys were administered to 81 WIC State agencies from 31 January 2022 to 1 April 2022. Descriptive statistics, independent samples t-test, and one-way analysis of variance were used to analyze the findings. Open-ended responses were analyzed using a qualitative iterative approach. WIC State agencies noted several barriers to implementing WIC online ordering, including limited staff capacity, WIC retailer interest, and technological capabilities.

Skin sensitization among night shift and daytime healthcare workers: a cross sectional study.

OBJECTIVE: Allergic contact dermatitis (ACD) in the healthcare sector is a major occupational health hazard. There are many reasons for a higher frequency of ACD in healthcare personnel compared to other populations: among others, simultaneous exposure to multiple substances, use of aggressive detergents and wet work. However, studies that systematically correlate skin symptoms with the presence of sensitization investigated through patch tests in specific categories of health workers are very rare and conflicting. Although some studies have reported a correlation between skin disease and night shift, the strength of the evidence is rather limited. The purpose of our study was to investigate by means of patch testing the skin sensitization (SS) to common allergens in the hospital setting in a group of healthcare workers (HCW) reporting symptoms related to dermatitis, according to their job activity and their shift status. METHODS: 132 HCWs visiting a health surveillance centre were investigated by means of specific questionnaire for dermatitis, followed by patch test evaluation including 40 haptens of the SIDAPA 2016 series. RESULTS: Skin sensitization was observed in 1/3 of the subjects investigated by patch tests. The nursing job was strongly associated with cutaneous reactivity after controlling for the confounding of gender, age and other factors. Shift work was related to the prevalence of SS. CONCLUSIONS: In our study, the nurse's role and shift work were significantly associated with the risk of cutaneous sensitization, in particular for common antigens.

Replicating patterns of prospect theory for decision under risk.

Prospect theory is among the most influential frameworks in behavioural science, specifically in research on decision-making under risk. Kahneman and Tversky's 1979 study tested financial choices under risk, concluding that such judgements deviate significantly from the assumptions of expected utility theory, which had remarkable impacts on science, policy and industry. Though substantial evidence supports prospect theory, many presumed canonical theories have drawn scrutiny for recent replication failures. In response, we directly test the original methods in a multinational study (n = 4,098 participants, 19 countries, 13 languages), adjusting only for current and local currencies while requiring all participants to respond to all items. The results replicated for 94% of items, with some attenuation. Twelve of 13 theoretical contrasts replicated, with 100% replication in some countries. Heterogeneity between countries and intra-individual variation highlight meaningful avenues for future theorizing and applications. We conclude that the empirical foundations for prospect theory replicate beyond any reasonable thresholds.

Severe facial reaction to thiurams in surgeons

Contact dermatitis is a major problem in the healthcare environment and in other sectors. Healthcare professionals may be exposed to a large number of chemical agents, including the accelerators for rubber vulcanization process. The prevalence of allergic contact dermatitis among operators in the sector ranges 13­30%. This paper describes the case of a 46-year-old male cardiac surgeon affected by a severe skin reaction localized on the face in the absence of hand dermatitis, presumably resulting from the use of a surgical patch applied to the face. Patch tests were performed and the result was negative for latex and positive (+++) for thiuram mix. A thiuram-free tape was prescribed and the operator's dermatitis improved significantly. Thus, it would be very important to pay attention to skin disorders in health workers and thiuram as an occupational allergen. Med Pr. 2019;70(1):121­4

Case Report: Occupational therapy in a patient with an overgrowth syndrome that restricts movement.

Background: Overgrowth syndromes are a heterogeneous group of conditions characterized by excessive body growth - localized or generalized - commonly associated with various malformities and an increased oncological risk. Case report: Here we present the case of a 57-year old man, employed in an office, who suffers from an asymmetric overgrowth of the lower limbs. Currently the patient presents malformations of the lower left arm (hip, knee and ankle), evident on the articular and periarticular level, where there are diffuse exostoses. This case discusses the main occupational concerns relating to the patient's workspace at a high floor level that could create critical issues in the event of an emergency exodus. Given the impossibility of placing the patient in heavy manual activities, employment is limited to office activities. Adjustments were carried out at the patient's workstation, and thus the patient has been recognized as fit to work. Increased frequency of breaks were prescribed in order to allow the physiological alternation of postures. Conclusions: In cases of overgrowth syndromes, the exact identification of the limitations presented by the patient and observations about ambulatory functions must be carefully evaluated in order to modulate the work environment.

Prevalence and Risk Factors for Latent Tuberculosis Infection among Healthcare Workers in a Low Incidence Country.

BACKGROUND: Tuberculosis prevention is a major goal in the hospital setting. Because of the possible progression or reactivation of latent disease, the screening of healthcare workers is an important issue in the TB control program. The aim of the study was to assess the prevalence of LTBI (latent tuberculosis infection) and to evaluate the main risk factors related to this condition in a teaching hospital in Italy. METHODS: We reviewed the data of a tuberculosis screening conducted on 3622 healthcare professionals in a teaching hospital in Rome. All subjects were evaluated by QuantiFERON test which if positive, was followed by appropriate clinical and diagnostic procedures. RESULTS: Latent Tuberculosis Infection LTBI condition was detected in 2.1% of the cases, most commonly in men. Male gender, higher age class, country of birth and nurse job were statistically related with the positivity to QuantiFERON test. CONCLUSION: LTBI was relatively uncommon in our population, however, given the potential risk of reactivation and progression to overt disease, the screening of healthcare workers and students is recommended in the hospital of low-incidence countries.

Are Shiftwork and Indoor Work Related to D3 Vitamin Deficiency? A Systematic Review of Current Evidences.

Background: Reported cases of vitamin D3 deficiency have been increasing in incidence worldwide. Although there is a lack of consensus relating to optimal levels of vitamin D, generally serum 25-(OH)D concentrations lower than 50 nmol/L (20 ng/mL) are at least considered to be detrimental to bone health. Aim: Aim of this systematic review is to investigate if occupations, and specifically shiftworking and indoor working, may be considered as possible contributors to the increased incidence of vitamin D3 deficiency in industrialized nations. Materials and Methods: Systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using PubMed, Scopus, and ISI Web of Knowledge databases. Results: Overall 90 papers were found, 23 articles through PubMed, 30 through Scopus, and 37 through ISI Web of Knowledge. Successively, 46 duplicates and 34 articles that did not respect the inclusion criteria were excluded. Finally 10 articles were selected: 9 cross-sectional studies and 1 systematic review. Results of the studies included revealed that certain occupations are either suffering from, or have a predilection to suffer from, a deficiency of this vitamin. Shiftworkers and indoor workers are consistently reported as being the occupational group most likely to suffer from a deficiency of vitamin D3. It would appear prudent to investigate the potential of providing nutritional education to workers in addition to including preventative measures in the workplace.

C-reactive protein predicts hematoma growth in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Early hematoma growth (EHG) occurs in about one third of patients with spontaneous intracerebral hemorrhage. The main aim of this study was to investigate the potential of plasma C-reactive protein (CRP) for predicting EHG after acute spontaneous intracerebral hemorrhage. METHODS: Plasma CRP was measured within 6 hours of onset (median, 120 minutes) in 399 patients with primary or vitamin K antagonist-associated spontaneous intracerebral hemorrhage and without recent infection. Computed tomography brain scans were performed at baseline and repeated within 24 hours (median, 22 hours). The primary outcome was EHG, defined as absolute growth>12.5 cm3 or relative growth>33%. Secondary outcomes included early neurological worsening (ENW) using the Glasgow Coma Scale and 30-day mortality. Multivariable regression analyses were used to evaluate associations of CRP concentration and outcomes. Kaplan-Meier analysis was used for survival. RESULTS: EHG occurred in 25.8%, ENW in 19.3%, and mortality was 31.8% at 30 days. Thirty-day mortality was significantly higher in patients with ENW (hazard ratio, 3.21; 95% confidence interval, 2.00-5.17; P<0.0001) and in patients with EHG (hazard ratio, 2.13; 95% confidence interval, 1.42-3.18; P<0.0001, log-rank test). Median CRP was 12 mg/L (interquartile range, 10-17) in the EHG group and 7 mg/L (interquartile range, 4-12.1) in those without EHG (P<0.0001). In multivariable analyses, plasma CRP>10 mg/L independently predicted EHG (odds ratio, 4.71; 95% confidence interval, 2.75-8.06; P<0.0001) and ENW (odds ratio, 2.70; 95% confidence interval, 1.50-4.84; P=0.0009). CONCLUSIONS: CRP>10 mg/L is independently predictive of EHG and ENW, both of which are associated with increased mortality. Inflammation may be important in contributing to EHG and warrants further investigation.

C-reactive protein in intracerebral hemorrhage: time course, tissue localization, and prognosis.

OBJECTIVES: We examined the C-reactive protein (CRP) response after spontaneous intracerebral hemorrhage (sICH) and its relationship to outcome. We additionally characterized early brain localization of CRP. METHODS: In this prospective, multicenter, international, collaborative, longitudinal study with cross-sectional immunohistochemical analysis of brain tissue, 223 patients (M/F: 132/91) were recruited during the 2010 calendar year. CRP was evaluated at admission (median 93 minutes from symptom onset), 24 hours, 48 hours, and 72 hours after sICH. Brains of 5 subjects with sICH were compared to brains of 2 aged controls without evidence of brain pathology and 7 patients with ischemic stroke. Plasma CRP was measured over 72 hours following sICH and its relationship to 30-day mortality and functional outcome at 30 days (Glasgow Outcome Scale) was determined. CRP immunostaining patterns were analyzed in samples of sICH autopsy brains. RESULTS: Plasma CRP increased over the 48 hours from admission and was significantly (p < 0.001) related to hematoma volume at later time points. The predictive utility of CRP for morbidity and mortality were maintained when adjusted for other risk factors and improved at 48 hours and 72 hours when compared with admission values. Although an early CRP localization was present in both ischemic and hemorrhagic lesions, an intense and diffuse neuropil staining was only present in sICH patients and particularly evident proximal to the hemorrhagic areas. CONCLUSIONS: Plasma CRP production increases markedly over the 48 hours to 72 hours period following sICH and is related to outcome. CRP is also present in large amounts around the hemorrhagic lesion and within neurons and glia of patients who died within 12 hours of sICH.

Role of C-reactive protein in cerebrovascular disease: a critical review.

C-reactive protein (CRP) is a blood marker of inflammation and a hallmark of the acute-phase response. Its elevation bears negative prognostic implications for many conditions and it has also been shown to be a nonspecific predictor of long-term risk of cerebrovascular disease (CVD) in several populations, while elevations of CRP associated with the major acute-phase response following ischemic or hemorrhagic stroke are associated with death and vascular complications. High-sensitivity assays that accurately measure levels of CRP have been proposed for use in risk assessment for CVD and as a prognostic marker after an acute event, although the pathogenic and clinical significance of these associations is controversial. In this article, we critically review the literature in narrative format and describe major epidemiological studies, novel experiments and possible future developments that may inform the debate. In our discussion, we will distinguish the different pathophysiological roles of high circulating CRP concentrations in individuals with acute stroke from the modestly and persistently increased levels of CRP concentration in generally healthy subjects. However, before any clinical application is possible, a critical appraisal of the strengths and deficiencies of the accumulated evidence is required, both to consider the current state of knowledge and to inform the design of future research.

C-reactive protein level measurement improves mortality prediction when added to the spontaneous intracerebral hemorrhage score.

BACKGROUND AND PURPOSE: Hyperglycemia and inflammation are involved in the progression of spontaneous intracerebral hemorrhage (sICH)-induced brain injury, but their role in predicting clinical outcome is not clear. We sought to determine whether elevation of white blood cell count (WBC), C-reactive protein (CRP), and blood glucose (BG) concentration at presentation prognosticate poor outcome in sICH patients. METHODS: Between November 1, 2005 and October 31, 2009, 210 patients admitted to 2 intensive care units were prospectively consecutively evaluated after exclusion of patients with underlying inflammatory conditions. WBC, CRP, and BG were measured and ICH scores were calculated on first evaluation. Primary outcome was 30-day mortality. Secondary outcome was 30-day functional outcome using the Glasgow Outcome scale. RESULTS: The median CRP concentration was 7.85 mg/L (interquartile range, 4.0-12.0 mg/L), median WBC count was 8.05×10(9)/L (interquartile range, 6.45-9.9×10(9)/L) and median glucose concentration was 7.66 mmol/L (interquartile range, 6.11-10.83 mmol/L). At 30 days, 63 patients (30%) were dead and 101 (48.1%) had poor outcome (Glasgow Outcome scale score, 1-3). Higher WBC (P<0.001), CRP (P<0.05), and BG (P<0.001) were associated with mortality on univariate analyses, but only CRP remained associated with mortality (P<0.005) after adjustment for multiple confounders. CRP improved mortality prediction when added to the ICH score. None of the markers tested had significant associations with functional outcome. CONCLUSIONS: Higher WBC, CRP, and BG are associated with increased mortality in sICH patients. Only CRP elevation portends higher risk of death independently of other indicators of sICH severity.

Hyperglycemia and short-term outcome in patients with spontaneous intracerebral hemorrhage.

BACKGROUND: Hyperglycemia has a detrimental effect in several acute neurological critical illnesses. No consensus exists on the optimal management of hyperglycemia in spontaneous intracerebral hemorrhage (sICH). Our aim was to determine whether blood glucose (BG) would predict 30-day mortality in sICH. METHODS: All patients with a well-defined diagnosis of sICH admitted into 24 h in three primary referred centers were included in this prospective observational follow-up study. Patients had extensive monitoring of BG values and those with BG values >8.29 mmol/l (150 mg/dl) received a variable intravenous insulin dose to maintain BG concentrations during the first 72 h after sICH between 3.32 and 8.29 mmol/l (60-150 mg/dl) using pre-specified insulin dosing schedule protocol. RESULTS: Between January 1, 2002, and December 31, 2003, 295 consecutive patients (mean +/- SD age 66 +/- 12 years) were prospectively included. A 1.0 mmol/l (18 mg/dl) increase in the BG concentration at admission was associated with a 33% mortality increase (OR: 1.33; 95%CI: 1.22-1.46; P < 0.0001). Adjusting for demographics, risk factors, stroke severity, and surgery there was no change in the increased risk. During the first 12 h after sICH, the insulin treatment protocol was enabling to reduce mortality (OR: 1.36, 95%CI: 1.14-1.61; P = 0.0005, per 1 IU increase) while thereafter this association was greatly attenuated and not more significant. CONCLUSIONS: Hyperglycemia is a common condition after sICH and may worsen prognosis. Very early insulin therapy apparently does not improve prognosis. These results raise concern about routine clinical practice implementation of this intervention without any evidence from randomized trials.

[Present insights in the cerebral small vessel disease physiopathology: the role of C-reactive protein]. / Sulla fisiopatologia dei piccoli vasi cerebrali: il ruolo della proteina C-reattiva.

The mechanisms underlying the pathogenesis of cerebral small vessel disease (SVD) are incompletely understood, although it represents a large burden upon healthcare and social service. New experimental and clinical data suggest that inflammatory reactions may play a crucial role in both the initiation and progression of SVD. Inflammatory processes could be involved in the pathogenesis of SVD, and particularly in the development of white matter lesions and leukoaraiosis. These new data regarding the possible effects of inflammatory reactions in SVD may be of more than just academic interest. It may be that adding evaluation of inflammatory markers, such as C-reactive protein, to conventional risk factors will allow more appropriate preventive and therapeutic interventions.

Systemic inflammation, blood pressure, and stroke outcome.

Hypertension is the most important modifiable risk factor for ischemic stroke, and antihypertensive treatment is of paramount importance to reduce the incidence of stroke mortality and morbidity. The significance and best management of hypertension during the first hours after stroke onset, however, are still matters of debate. Cerebral ischemia results in a complex inflammatory cascade; inflammatory mechanisms are also important participants in the pathophysiology of hypertension. There has been a convergence of evidence that is important to consider in managing systemic blood pressure after stroke to ensure an optimal outcome. The identification of useful markers will allow progress in our ability to treat blood pressure in the acute phase of a stroke. The determination of levels of C-reactive protein, an acute-phase inflammation marker, may help to guide our approach in the management of blood pressure in acute ischemic stroke. Whether this target will be useful in the development of risk prediction strategies or therapies for the treatment of stroke in humans is far from clear.

Human naive CD4 T-cell clones specific for HIV envelope persist for years in vivo in the absence of antigenic challenge.

To study the persistence of HIV-specific human naive CD4-lymphocytes in vivo in the absence of antigenic stimulation, we identified 2 HIV-seronegative low-risk subjects carrying CD4-cells specific for gp120 that could be expanded in vitro. CD4 T-cell lines specific for gp120 were generated by stimulation cycles with antigen-pulsed antigen-presenting cells. Clonal analysis was performed by spectratyping and by sequencing of the CDR3 regions of the BV and AV-T-cell receptor (TCR) genes. HIV-specific T cells were expanded in vitro in 1989 and 2004. These lines were generated from naive precursors. Analysis of TCR-BV gene family use and sequencing of the TCR-BV22 hypervariable region revealed a BV22 clonotype in the 1989 line. The BV22-CDR3-based polymerase chain reaction primer confirmed that the 1989 and 2004 T-cell lines contained the same clonotype. In addition, the 1989 and 2004 T cells used the same TCR-AV38 gene family and identical CDR3-AV regions, confirming clonal identity. Similar data for a persistent clonotype defined by BV CDR3 sequencing were obtained from the second subject. In conclusion, naive CD4-cells specific for an HIV antigen not encountered in vivo persisted for more than 10 to 15 years. An extended lifespan, homeostatic proliferation, or the ability of the thymus to issue the same CD4 T-cell clone reiteratively might account for the phenomenon.

Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the CRP Pooling Project members.

BACKGROUND AND PURPOSE: Several studies have shown, in different populations, that modest elevation of plasma C-reactive protein (CRP) in the range seen in apparently healthy individuals is a strong predictor of future vascular events. Elevated plasma CRP concentrations are also associated with an increased risk of cerebrovascular events and an increased risk of fatal and nonfatal cardiovascular events in ischemic stroke patients. These epidemiological and clinical observations suggest that determination of plasma CRP concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease and be of prognostic value. The aim of this review is to summarize the evidence for CRP as an independent predictor of cerebrovascular events in at-risk individuals and ischemic stroke patients and to consider its usefulness in evaluating prognosis after stroke. SUMMARY OF REVIEW: CRP fulfils most of the requirements of a new risk and prognostic predictor, but several issues await further confirmation and clarification before this marker can be included in the routine evaluation of stroke patients and subjects at risk for cerebrovascular disease. Potentially important associations have been established between elevated plasma CRP concentrations and increased efficacy of established therapies, particularly lipid-lowering therapy with statins. CONCLUSIONS: At present, there is not sufficient evidence to recommend measurement of CRP in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated CRP adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this.