Radiation Recall Pneumonitis COVID-19 Infection Induced After Adjuvant Breast Cancer Radiotherapy. A Known Phenomenon in an Unknown Pandemic Disease: A Case Report.

The COVID-19 pandemic has opened several new disease scenarios, yielding novel syndromes that have never been seen before and resurrecting old inflammatory phenomena that are no longer recorded, such as radiation recall (RR) syndromes. Radiation recall syndrome is a limited field inflammatory reaction that occurs in a volume that was irradiated several months or years previously before being induced by a triggering factor. The most frequently reported phenomena are skin reactions; however, other organs could be involved, such as the lungs in radiation recall pneumonitis (RRP). It is a well-described inflammatory reaction that occurs within a pulmonary volume that was irradiated several months or years previously via radiotherapy (RT), triggered by factors such as drugs, including chemotherapy agents, immunotherapy, or vaccination. Indeed, during the COVID-19 pandemic, RRP following anti-COVID-19 vaccination or SARS-CoV2 infection was recently reported. ACE receptor-rich tissues such as lung or skin tissues were mainly involved. Herein, we present a case of RRP triggered by COVID-19 pulmonary infection in a woman who previously underwent adjuvant breast cancer radiotherapy. Although symptoms were typical, pulmonary CT findings depicted a unique distribution of ground-glass opacities (GGOs) throughout the previous radiation portals and mirror-like the radiation fields. Anamnesis and radiation plan evaluation were crucial in the diagnosis of RRP.

Estimation of Pleural Effusion Volume through Chest Ultrasound: Validation of Two Multiplanar Models.

Computed tomography (CT) scanning is the gold standard when estimating pleural effusion volume; however, the procedure exposes patients to ionizing radiation. Our study was aimed at developing ultrasound-based calculation models that can quantify the volume of pleural effusion in seated patients and validating each model using volumetric chest CT analyses as reference. Our study enrolled 36 hospitalized patients who underwent a chest CT scan and ultrasound, in the seated position, with the aid of a convex probe. To estimate the volume of pleural effusions, we applied one linear and two multiplanar ultrasound-based equations using a CT reconstruction as reference. Testing these models in our validation set (n = 16), we determined that 0.42 was the R2 coefficient for the linear equation, and 0.97 and 0.98, respectively, were the R2 coefficients for the cylindrical-sector models, and observed that the latter had the lowest dispersion of data and an optimal intraclass correlation coefficient. We then concluded that multiplanar ultrasound-based equations are accurate and reliable in estimating pleural effusions and outperform previously developed equations.

Resolution of inflammation is altered in chronic heart failure and entails a dysfunctional responsiveness of T lymphocytes.

Chronic heart failure (CHF) is characterized by an ongoing nonresolving inflammatory status, where T lymphocytes seem critical. It has been recently recognized that transition from acute to chronic inflammation could be caused by defects in resolving inflammation, the resolution of which is mediated by a novel family of ω-3-derived specialized proresolving lipid mediators such as resolvins. We analyzed 27 elderly patients with CHF and 23 healthy age-matched control subjects, and we reported significantly lower levels of D-series resolvin (RvD)1 in plasma of patients with CHF that were associated with a reduced ability of their leukocytes to produce this lipid via its biosynthetic enzyme 15-lipoxygenase and that correlated with gas exchange dysfunction. Furthermore, when pretreating ex vivo peripheral blood mononuclear cells of patients with CHF with RvD1 or RvD2, we found that neither of them was able to modulate the immune response of CD8+ and CD4+ T cells in terms of proinflammatory cytokine production, namely TNF-α, IFN-γ, IL-17, and IL-2. Such impaired T-cell responsiveness in patients with CHF was associated with a significant reduction in mRNA and protein expression of RvD1 receptor GPR32, suggesting a defective signaling in the proresolving pathway. We conclude that patients with CHF show alterations in producing proresolving mediator RvD1 and a failure of adaptive immune cells in responding to the anti-inflammatory actions of RvDs that may contribute to the progression of chronic inflammation. Thus, the proresolution pathway might be a potential candidate to design better treatments for CHF aimed at reducing T cell-mediated chronic inflammation.-Chiurchiù, V., Leuti, A., Saracini, S., Fontana, D., Finamore, P., Giua, R., Padovini, L., Incalzi, R. A., Maccarrone, M. Resolution of inflammation is altered in chronic heart failure and entails a dysfunctional responsiveness of T lymphocytes.

GOLD Staging System is Appropriate to Predict Mortality in Older People With Chronic Obstructive Pulmonary Disease.

INTRODUCTION: In the new GOLD classification the reduction of FEV1, expressed as percentage of predicted value (FEV1PP), is considered an important prognostic factor. However, the use of FEV1PP may introduce bias, especially if based on equations derived from populations different from the one under study. We evaluated how well the GOLD classification stratifies the mortality risk when FEV1PP is based on an equation developed in the same population that gave rise to cases, externally developed equations, or as FEV1 divided by cubed height (FEV1/Ht3). METHODS: We studied 882 participants aged ≥65 years. Bronchial obstruction was defined using a fixed cut-off of 0.7 for FEV1/FVC. Predicted values of FEV1 were derived from equations based on the same sample of the cases included in this study and from the European Respiratory Society equations. Severity of bronchial obstruction was also classified according to quartiles of FEV1/Ht3. RESULTS: All the classification systems showed a non-statistically significant linear tendency with 5-years mortality risk. For the 15-years mortality, the linear trend across severity stages is more evident for GOLD classifications, with significant increments in the hazard ratio. Stratification by FEV1/Ht3 could better discriminate the functional status of participants. CONCLUSION: The severity of bronchial obstruction according to GOLD classes may stratify mortality risk better than quartiles of FEV1/Ht3, whereas the second seems to be more suited to stratify the risk of clinical outcomes. Concerns about the use of externally developed reference values to calculate FEV1PP do not seem confirmed, at least for GOLD classification.

Difference in Mortality Risk in Elderly People with Bronchial Obstruction Diagnosed Using a Fixed Cutoff or the Lower Limit of Normal of the FEV1/FVC Ratio.

BACKGROUND: Whether a fixed cutoff or the lower limit of normal of the FEV1/FVC ratio should be used to diagnose bronchial obstruction is still a matter of debate. This issue is particularly important for elderly people. OBJECTIVES: We used equations applicable up to 90 years of age to evaluate the mortality of elderly people diagnosed with bronchial obstruction using either a fixed cutoff of 0.7 or the lower limit of normal (LLN). METHODS: Participants in the SaRA (Salute Respiratoria nell'Anziano, Italian for "Respiratory Health in the Elderly") study were grouped as follows: FEV1/FVC ≥0.7 and ≥ LLN (n = 535: F-/L-), FEV1/FVC <0.7 but ≥ LLN (n = 118: F+/L-), and FEV1/FVC <0.7 and < LLN (n = 229: F+/L+). We estimated the mortality risk in the three groups over 15 years of follow-up. RESULTS: The mean age was 73 years (58% men). The hazard ratio (HR) for mortality was 1.427 (95% CI: 1.09-1.868) in the F+/L- group and 2.143 (95% CI: 1.13-1.995) in the F+/L+ group. After adjustment for potential confounders, we found no increased mortality in the F+/L- group (HR: 1.007, 95% CI: 0.755-1.342), while the HR in the F+/L+ group was still sizeable (1.474, 95% CI: 1.136-1.911). CONCLUSIONS: As expected, using a fixed cutoff translates in a larger number of people to be classified as having bronchial obstruction. In our sample the increased mortality in the F+/L- group is due to the confounding effect of age and sex. Our study lends support to the use of LLN in elderly people.

Impact of statin therapy on plasma leptin concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials.

OBJECTIVES: The effects of statins on insulin sensitivity, metabolic homeostasis and adipokines in humans are controversial. Several studies have investigated the impact of statin therapy on plasma leptin concentrations but the results have been inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis of available evidence to calculate the effect size of statin therapy in changing serum leptin concentrations. METHODS: A systematic search in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases was performed to identify randomized placebo-controlled trials investigating the effect of statins on plasma leptin concentrations. A random-effects model and generic inverse variance method were used for meta-analysis. Sensitivity analysis, risk-of-bias evaluation and publication bias assessment were carried out using standard methods. Random-effects meta-regression was used to evaluate the impact of treatment duration on the estimated effect size. RESULTS: Six trials, with a total of 425 subjects, met the eligibility criteria. Overall, statin therapy had no significant effect on leptin levels (weighted mean difference -0.32 ng ml-1 , 95% confidence nterval: -2.94, 2.30, P = 0.813). This effect was robust in the sensitivity analysis and in subgroup analyses of trials with <12 or ≥12 weeks' duration. There was no association between the duration of statin therapy and changes in plasma leptin levels. Furthermore, there was no differential effect of hydrophilic and lipophilic statins on plasma leptin concentrations. CONCLUSION: Unless more consistent evidence becomes available in the future, the hypothesis of a relationship between statin use and serum leptin concentrations seem to be unfounded.

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials.

Flow-mediated dilation (FMD) of the brachial artery reflects endothelium-dependent vasodilator function; since it correlates with coronary endothelial function, its reduction could predict cardiovascular events. Several studies have investigated the potential impact of fibrates therapy on endothelial function, but clinical findings have not been fully consistent. We aimed to conduct a meta-analysis of randomized placebo-controlled trials in order to clarify whether fibrate therapy could improve endothelial function. A systematic search in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases was performed to identify randomized placebo-controlled trials investigating the effect of fibrates on endothelial function as estimated by FMD. A random-effects model and generic inverse variance method were used for meta-analysis. Sensitivity analysis, risk of bias evaluation, and publication bias assessment were carried out using standard methods. Random-effects meta-regression was used to evaluate the impact of treatment duration on the estimated effect size. Fifteen trials with a total of 556 subjects met the eligibility criteria. Fibrate therapy significantly improves FMD (weighted mean difference [WMD]: 1.64%, 95% CI: 1.15, 2.13, p<0.001) and the result was confirmed in both subgroups with treatment durations ≤8 weeks (WMD: 1.35%, 95% CI: 0.85, 1.86, p<0.001) and >8 weeks (WMD: 2.55%, 95% CI: 1.21, 3.89, p<0.001). When the analysis was stratified according to the fibrate type, a significant effect was observed with fenofibrate but not with gemfibrozil, though difference between the two subgroups was not significant. Meta-analysis of data from trials where nitrate mediated dilation (NMD) was available did not suggest a significant change in NMD following treatment with fibrates. The results of this meta-analysis suggest that fibrates may exert beneficial effects on endothelial function, even over a short-term treatment course.

Relationship between respiratory muscle strength and physical performance in elderly hospitalized patients.

UNLABELLED: Background: Age-related changes in pulmonary function increase respiratory muscle work. In the face of this increased demand, poor muscle mass, frequently associated with age and multi-morbidity, can reduce endurance and strength of respiratory muscles. Furthermore, poor muscle mass may per se contribute to exercise intolerance and lower physical performance. The aim of the study was to evaluate if respiratory muscle strength has a significant impact on physical performance in an elderly population. METHODS: We included 68 patients (28 men and 40 women) aged over 65 years (mean 79 years, standard deviation [SD] 6) in stable condition at discharge from our acute care geriatric ward. We assessed the function of respiratory muscle by measuring maximal inspiratory and expiratory pressures (MIP, MEP) and physical function using the 6-Minute Walk Test (6MWT). RESULTS: The mean age of our sample was 78.2 years (SD 6.1). There was a statistically significant correlation between MIP or MEP and 6MWT distance (MIP, r=0.43, p<0.001; MEP, r=0.41, p=0.001). The association between respiratory pressures and 6MWT was maintained after adjustment for forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), age, sex, fat-free mass index (FFMI), and leg strength. The multiple regression model showed a significant relation between 6-Minute Walk Test distance (6MWD) and both MIP and MEP after correction for sex, age, FEV1, and FVC. Furthermore, MEP can significant predict poorer performance at 6MWD in a multiple logistic regression model. CONCLUSION: Reduced respiratory muscle strength is independently associated with worse physical performance in elderly patients.

Interventions against sarcopenia in older persons.

The term "sarcopenia" describes the age-related loss of skeletal muscle mass and function. It represents a major risk factor for functional loss and disability in older persons. Multiple underlying pathophysiological mechanisms have been posed at the basis of the sarcopenia phenomenon, including intrinsic (e.g., age-related modifications of the skeletal muscle, the central nervous system, and hormones) and extrinsic (e.g., sedentariness, poor protein dietary intake) factors. Several interventions have been explored in the last years to counteract the age-related muscle decline. These include protein supplementations, physical exercise, testosterone replacement (as well as other anabolic androgens) in men, estrogen replacement in women, growth hormone replacement, and treatment of vitamin D deficiency. To date, adequate protein intake and resistance training are the most promising interventions able to prevent and/or delay the decline of muscle mass and function. An intense debate is currently ongoing about the best operational definition able to capture the complexity of this aging condition. In the context of identifying the optimal treatment for a specific condition, this is not a trivial issue because it sets the target of the intervention as well as the population at risk. Nevertheless, despite the current methodological issues, it is important to preliminarily test the possible strategies that might be implemented in the future, when the sarcopenia condition will finally be more univocally defined and its clinical relevance recognized. Aim of the present review is to describe and discuss available evidence about the possible interventions potentially serving at acting against sarcopenia. Pharmacological as well as non-pharmacological interventions are presented.

Fever of unknown origin in a very old patient: beware of the kidney!

ANCA-associated vasculitis affects more than 20 per million of the population per year and prevails in the elderly. Renal involvement, either isolated or in the context of systemic vasculitis, is common. We report the case of an 86-year-old patient who presented with a histologically proven renal limited vasculitis and with fever and fatigue but with normal renal function and urine analysis. Serum creatinine increased and microscopic hematuria became evident only 3 weeks after symptoms onset, whereas ANCA positivity was the only early key to the diagnosis. This case shows that in the elderly an ANCA-related pauci-immune glomerulonephritis in its earliest stages should be suspected in the presence of a fever of unknown origin even if serum and urine analyses are normal.

Physical function and exercise in older patients with cardiovascular and respiratory conditions.

The increase of life expectancy together with the decline of birth rates implies a global aging of populations living in industrialized countries. Since advanced age is associated with an exponential consumption of health care resources, this phenomenon is likely to pose a substantial threat to the stability of public health systems. Prevention of physical disability represents a major public health priority. Since disability is considered an irreversible condition, every effort should be made to prevent the onset of the disabling cascade and/or delay the physical function decline. The need for strategies against disability has led researchers to look for the most relevant risk factors potentially determining or accelerating the disabling cascade. In this context, cardiovascular and respiratory conditions have been indicated as playing prominent roles in the determination of frailty. Moreover, the high prevalence of these conditions among older persons makes them particularly amenable to targeting for preventive interventions. The aim of the present review is to show the impact of cardiovascular and respiratory conditions on physical function. Moreover, we will discuss the relationship of these conditions with the disabling process, and the importance of their assessment in the design of preventive interventions against disability in older persons.

Lung function changes in older people with metabolic syndrome and diabetes.

AIM: Restrictive lung dysfunction (RLD; defined as reduced forced vital capacity [FVC] in the presence of normal forced expiratory volume in 1 s [FEV1]/FVC ratio) is highly prevalent in the elderly, and is associated with diabetes, metabolic syndrome (MetS) and abdominal obesity. The aim of this study was to assess the relative contribution of diabetes, MetS and abdominal obesity in characterizing RLD in the elderly. METHODS: This was cross-sectional analysis of 192 consecutive, community-dwelling persons (mean age 70.8 ± 8 years). The participants were grouped according to the number of MetS components (i.e. 0, 1, 2, 3 or 4) and the presence of diabetes. According to the Adult Treatment Panel-III criteria, participants with three or four components were considered to be affected by MetS. Independent correlates of RLD and obstructive lung dysfunction (OLD; FEV1/FVC < 0.70) were assessed by logistic regression models. RESULTS: The mean age of the sample population was 70.8 years. FVC expressed as percent of the predicted value declined for an increasing number of MetS components (P < 0.0001), but diabetes did not account for further ventilatory decline. Consistently, MetS (OR 3.03, 95% CI 1.16-7.89) and abdominal obesity (OR 4.89, 95% CI 1.17-20.3), but not diabetes, were independently associated with RLD. OLD did not worsen for an increasing number of MetS components and was only related to age (OR 1.07, 95% CI 1.01-1.13) and smoking (OR 1.04, 95% CI 1.01-1.06). CONCLUSIONS: MetS and abdominal obesity, two conditions of prediabetes, but not diabetes itself, are closely associated with RLD. These conditions might be implicated in the pathogenesis of the RLD, which is frequently observed in diabetic patients.

Diagnosis and prognostic value of restrictive ventilatory disorders in the elderly: a systematic review of the literature.

Although less extensively studied compared to pulmonary obstructive diseases, restrictive lung disease (RLD) is highly prevalent and frequently disabling in the adult and, more, the elderly population. The underlying conditions may be either primarily pulmonary diseases, such as idiopathic pulmonary fibrosis, or non respiratory conditions secondarily affecting the lung, e. g. congestive heart failure, or else conditions affecting the lung expansion, e. g. obesity or rib cage deformity. The diagnosis is frequently based on the measurement of surrogate indexes such as the forced vital capacity (FVC) used as a proxy for total lung capacity (TLC). As a consequence, diagnosis of RLD is often characterized by poor specificity. In the elderly, worsening in the quality of life and poor prognosis are variably, but significantly, associated to RLD, being the underlying condition an important source of variability. Several causes of RLD are preventable and treatable conditions. A prompt identification of these conditions may allow to slow the decline of respiratory reserve and, thus, to preserve both personal independence and resistance to acute respiratory infections. This review gives an update on the latest evidence available on the prevalence and the prognosis of RLD in the elderly. Studies were identified through systematic searches of the electronic database MEDLINE. Reference list of eligible papers were also manually searched.

Unexpectedly high rates of obesity and dysglycemia among villagers in Cameroon.

Our survey in Cameroon recorded obesity and dysglycemia in inhabitants, which are similar to those reported elsewhere in the region. Typically these metabolic disturbances are attributed to the adoption of a new urban lifestyle including diminished physical activity and an altered ('Western') diet. Unexpectedly we found that, like urban populations, our rural population had high rates of metabolic disturbances, despite living in villages and being physically active and consuming traditional diet that is high in plant sources of food and low in meat. From our preliminary study, we raise the possibility that the environmental elements that are driving the pandemic of obesity and diabetes in sub-Saharan Africa are far more complex than heretofore appreciated.