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.

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

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.

Long road towards effective HER3 targeting in breast cancer.

Breast cancer is a heterogeneous disease, encompassing multiple different subtypes. Thanks to the increasing knowledge of the diverse biological features of each subtype, most patients receive personalized treatment based on known biomarkers. However, the role of some biomarkers in breast cancer evolution is still unknown, and their potential use as a therapeutic target is still underexplored. HER3 is a member of the human epidermal growth factors receptor family, overexpressed in 50%-70% of breast cancers. HER3 plays a key role in cancer progression, metastasis development, and drug resistance across all the breast cancer subtypes. Owing to its critical role in cancer progression, many HER3-targeting therapies have been developed over the past decade with conflicting findings. Next-generation antibody-drug conjugates have recently shown promising results in solid tumors expressing HER3, including breast cancer. In this review, we discuss the HER3 role in the pathogenesis of breast cancer and its relevance across all subtypes. We also explore the new anti-HER3 treatment strategies, calling into question the significance of HER3 detection as crucial information in breast cancer treatment.

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.

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.

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.

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.

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.

[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.

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.

M-40403 Metaphore Pharmaceuticals.

Metaphore Pharmaceuticals Inc. is developing M-40403, a superoxide dismutase mimetic, for the potential treatment of pain, dermatological disease and inflammation. The company is also investigating the compound for its potential in the treatment for the side effects associated with chemotherapy and radiation therapy.

Angiotensin-converting enzyme inhibitor use is associated with reduced plasma concentration of C-reactive protein in patients with first-ever ischemic stroke.

BACKGROUND AND PURPOSE: High levels of C-reactive protein (CRP) are associated with an increased risk of future cardiovascular events in ischemic stroke. It has been hypothesized that the benefit of angiotensin-converting enzyme (ACE) inhibitors in patients at high vascular risk may also result from their anti-inflammatory action. Data evaluating this hypothesis are limited in ischemic stroke. METHODS: We conducted a prospective observational study in 507 patients with first-ever ischemic stroke to analyze the effect of ACE inhibitor treatment at the time of stroke onset on CRP levels within the first 24 hours and the relationship to outcome. Risk estimates were calculated according to Cox regression analysis controlled for blood pressure (BP) levels, clinical and neuroradiological confounding variables, and log-normalized CRP levels at entry. RESULTS: ACE inhibitor treatment was associated with lower (2.6-fold; P<0.0001) median CRP levels and with a reduced 2-year cardiovascular risk (hazard ratio, 0.39; 95% CI, 0.29 to 0.53; P<0.0001) compared with a different BP-lowering regimen. The relationship between ACE inhibitor status and log-normalized CRP levels remained significant (P<0.0001) after we controlled for important confounding variables and concomitant treatments. The reduced risk was also evident in multivariable analysis when ACE inhibitor treatment was controlled for BP, associated risk factors, neuroradiological findings, and concomitant treatments (hazard ratio, 0.43; 95% CI, 0.30 to 0.62; P<0.0001). This risk reduction was greatly attenuated and not more significant when log-normalized CRP levels were included (hazard ratio, 0.67; 95% CI, 0.43 to 1.04; P=0.0721) in the model. CONCLUSIONS: Concomitant treatment with ACE inhibitor at the time of an acute stroke is associated with lower inflammatory response and better long-term outcomes, apparently apart from the effects on BP.

Inflammation, hemostatic markers, and antithrombotic agents in relation to long-term risk of new cardiovascular events in first-ever ischemic stroke patients.

BACKGROUND AND PURPOSE: The measurement of markers of inflammation or thrombosis has been proposed as a method to improve the prediction of risk in patients with vascular disease. We evaluated the usefulness of these markers as predictors of cardiovascular events in ischemic stroke patients. METHODS: We analyzed levels of C-reactive protein (CRP), fibrinogen, and D-dimer within the first 24 hours after stroke onset in 473 first-ever ischemic stroke patients and determined the cumulative survival curves free of cardiovascular events in relation to the level of each of these markers according to the Kaplan-Meier method. We adjusted for possible confounding variables using a multivariate Cox proportional-hazards model. RESULTS: Patients in the highest tertiles of D-dimer, fibrinogen, and CRP were associated with an excess risk of new cardiovascular events of 36% (P=0.0134), 63% (P<0.0001), and 72% (P<0.0001), respectively, compared with patients in the lowest tertile. The patients in the highest tertile of CRP had 4 times the risk (hazard ratio, 4.04; P<0.0001) of a new cardiovascular event. Smoking, age, sex, and body mass index did not modify risk, and risk was independent of other confounding variables and of D-dimer and fibrinogen levels. The use of ticlopidine was associated with a significant risk reduction among patients with lower (86%, P=0.0159) and middle (69%, P<0.0001) levels of CRP, whereas a nonsignificant excess risk (27%, P=0.3896) was evident among those with the highest levels. CONCLUSIONS: Elevated levels of CRP, more than of D-dimer and fibrinogen, are related to the risk of new cardiovascular events after ischemic stroke. The efficacy of antiplatelet therapy in secondary prevention appears to be directly related to level of inflammatory and thrombotic markers.

The proteasome system and proteasome inhibitors in stroke: controlling the inflammatory response.

The ubiquitin-proteasome pathway (UPP) is a predominantly non-lysosomal protein degradation pathway responsible for degrading many critical regulatory proteins (e.g., nuclear factor-kappa B). This pathway is widely known for its ubiquitous role in immune and inflammatory responses, control of cell growth and apoptosis. These roles are apparent in the nervous system, but neurons and their neighboring cells also employ the UPP for distinct functions, ranging from development to the co-ordination of cellular responses, injury of the nervous system and brain-specific processes such as aging and memory. Promising results from preclinical studies in animal models indicate that the use of specific proteasome inhibitors to manipulate UPP may prove valuable in treating such conditions as ischemic stroke.

MLN-519. Millennium/PAION.

Millennium Pharmaceuticals Inc (formerly LeukoSite Inc) and PAION GmbH are developing MLN-519, a ubiquitin/proteasome enzyme inhibitor, for the potential treatment of inflammatory diseases and stroke. MLN-519 is currently undergoing phase I clinical trials in acute stroke and myocardial infarction, and is poised to enter phase II trials.

NCX-4016 NicOx.

NCX-4016 is a nitric oxide-aspirin conjugate non-steroidal anti-inflammatory drug that is under investigation by NicOx for the potential treatment of cardiovascular disorders and colon cancer. In April 2002, a phase II clinical trial was initiated in symptomatic peripheral arterial disease, and in March 2003, the University of Michigan was awarded a grant by the NIH to conduct a phase II trial in individuals at risk of colon cancer.