Are preoperative parameters of unilateral pyelo-ureteric junction obstruction in children predictive of postoperative function improvement?

OBJECTIVES: Surgery on the pyelo-ureteric junction obstruction (PUJO) has long been thought to affect postoperative renal function. However, preoperative assessment of which kidneys will benefit from such surgery remains unreliable. MATERIAL AND METHODS: Pre- and postoperative data relating to renal function were obtained by renal scan for 69 patients who were operated upon for PUJO. These patients were divided into two groups: group A (improved differential renal function) and group B (unimproved or decreased differential renal function). The two groups were then compared with regard to age at operation and presence or absence of clinical symptoms. Ultrasound (anteroposterior diameter of the pelvis, parenchymal thickness) and renal scan (glomerular filtration rate, differential renal function of the affected kidney, obstructive pattern) parameters were also taken into consideration. Some variables were also made dichotomous (pelvic diameter < or > 15 mm, parenchymal thickness < or > 5 mm, differential renal function < or > 40%). Statistical correlation was sought with parametric and non-parametric tests. RESULTS: No correlation whatsoever was found between the two groups for any of the parameters under consideration, so that any attempt at logistical regression analysis failed. CONCLUSIONS: None of the currently adopted diagnostic tests can be used to indicate which renal units will benefit from surgery through an improved renal function. The presence or absence of clinical symptoms does not appear to affect renal function either. There is evidence that parents should be provided with such information when giving their informed consent to pyeloplasty.     

Mental health,financial, and social outcomes among older adults with probable COVID-19 infection: A longitudinal cohort study

We investigated the immediate and longer-term impact (over 4-6 months) of probable COVID-19 infection on mental health, wellbeing, financial hardship, and social interactions among older people living in England. Data were analysed from 5146 older adults participating in the English Longitudinal Study of Ageing who provided data before the pandemic (2018-19) and at two COVID-19 assessments in 2020 (June-July and November-December). The associations of probable COVID-19 infection (first COVID-19 assessment) with depression, anxiety, poor quality of life (QoL), loneliness, financial hardship, and social contact with family/friends at the first and second COVID-19 assessments were tested using linear/logistic regression and were adjusted for pre-pandemic outcome measures. Participants with probable infection had higher levels of depression and anxiety, poorer QoL, and greater loneliness scores compared with those without probable infection at both the first (OR_depression = 1.62, P-value = 0.005; OR_anxiety = 1.59, P-value = 0.049; b_poorQoL = 1.34, P < 0.001; b_loneliness = 0.49, P < 0.001) and second (OR_depression = 1.56, P-value = 0.003; OR_anxiety = 1.55, P-value = 0.041; b_poorQoL = 1.38, P-value < 0.001; b_loneliness = 0.31, P-value = 0.024) COVID-19 assessments. Participants with probable infection also experienced greater financial difficulties than those without infection at the first assessment (OR = 1.50, P-value = 0.011). Probable COVID-19 infection is associated with longer-term deterioration of mental health and wellbeing and short-term increases in financial hardship among older adults. It is important to monitor the mental health of older people affected by COVID-19 and provide additional support to those in need.

The coronavirus disease 2019 (COVID-19) pandemic has affected several aspects of people’s lives, including physical and mental health, employment and financial security, social connections, and access to healthcare (1). Despite a large body of research documenting the adverse psychosocial effects of the pandemic and its containment measures across the population, little is currently known regarding the impact that contracting COVID-19 itself may have on the individual’s mental health, personal finances, and social relationships.Several longitudinal studies have reported increases in depression, anxiety, and general psychological distress in the adult population during the COVID-19 pandemic compared with prepandemic levels (2, 3). People who have contracted COVID-19 might be particularly vulnerable to the psychological impact of the pandemic. Indeed, initial evidence suggests that the experience of COVID-19 symptoms is associated not only with adverse physical consequences, but also with long-term effects on mental health (4, 5). Various mechanisms could underlie the psychological effects of COVID-19 infection, including the potential neurotropic properties of the virus (6, 7); the presence of elevated proinflammatory cytokines (e.g., interleukin-6) in patients with severe COVID-19 symptoms (8), which are implicated in the development of psychiatric disorders such as depression (9); and the exposure to prolonged periods of social isolation and physical inactivity in people affected by COVID-19 (10), which in turn can increase mental distress and feelings of loneliness. Compounded by the widespread psychosocial effects of the pandemic across the population, these factors might further exacerbate the risk of mental health problems among individuals recovering from COVID-19 infection.Data from previous coronavirus epidemics demonstrate the potential psychiatric consequences of the virus in both the acute and postacute phases of the illness (11). Further, studies across different countries have found that individuals reporting COVID-19 symptoms and patients recovering from acute COVID-19 illness exhibit increased levels of anxiety, depression, suicidal ideation, loneliness, and poor quality of life (QoL) compared with healthy people (5, 12–19). Studies using data from electronic health records in the United States have also shown that COVID-19 patients with no previous psychiatric history are at increased risk of first-time diagnosis of psychiatric disorders compared with those affected by other health events (e.g., influenza) or healthy controls (20, 21). However, most studies to date are limited by small, nonrepresentative samples and short follow-up periods, and they lack longitudinal data on the participants’ mental health before COVID-19, as well as data on confounding factors. Since individuals with preexisting mental disorders seem particularly susceptible to COVID-19 infection (20, 22), it is unclear the extent to which reverse causality and confounding bias might contribute to the association between COVID-19 infection and psychological distress. In addition, studies involving electronic health records or clinical samples may not capture individuals with moderate COVID-19 symptoms and those with less severe mental health problems who do not present to health services.Longitudinal cohort studies are well suited to study the immediate and longer-term psychosocial consequences of COVID-19 infection in the general population, as they include comprehensive information on mental health before the infection and other confounding factors (e.g., sex, age, socioeconomic position). Results from the United Kingdom suggest that people with probable COVID-19 symptoms experience greater psychological distress up to 7 months following the start of the infection (23). In contrast, an online study in the United States found evidence only for short-term psychological effects that diminish as the symptoms subside (24). Notably, these studies have only focused on general psychological distress; therefore, the impact of COVID-19 infection on specific mental health and wellbeing outcomes (e.g., depression, anxiety, loneliness, and QoL) in the general population is unclear.Numerous studies have also highlighted the financial impact of the pandemic—including job losses, pay cuts, reductions in household income, fluctuations in stock markets and wealth held in risky assets, and widespread financial worries (25–27)—as well as its adverse consequences for various domains of social relationships, including social networks, social support, and social interaction (28, 29). However, these studies relate to the whole population rather than to people with COVID-19 infection. Empirical evidence regarding the impact that COVID-19 infection may have on a person’s financial situation and social relationships is limited. For instance, cross-sectional results suggest that adults who have experienced COVID-19 are more likely to report that their social relationships, work, and household finances have been adversely affected by the pandemic, compared with those who have not had COVID-19 (30). However, this analysis did not account for preexisting trends in social connections and economic outcomes, and it was unable to disentangle short-term versus longer-term psychosocial consequences of the infection.Older adults are at increased risk of social isolation and serious illness following COVID-19 infection (31), and they also are particularly vulnerable to the effects of chronic stress on the brain (32). A recent analysis of data from the English Longitudinal Study of Aging (ELSA) also demonstrates that the mental health and wellbeing of the older population deteriorated significantly as the pandemic progressed in 2020, compared with prepandemic levels (33). Given these factors, older people might be disproportionally affected by the psychosocial effects of COVID-19 infection. However, little research on COVID-19 has involved older adults who are also often unable to access online surveys (34). In addition, care-seeking behaviors changed considerably in the early stages of the pandemic, with large numbers of older adults with care needs not actively contacting health services and not seeking help (35). Therefore, older adults’ experiences of COVID-19 might be underrepresented in earlier studies.In the present analysis, we investigated the immediate and longer-term impact (over 4 to 6 months) of probable COVID-19 infection on mental health (i.e., depression and anxiety), wellbeing (i.e., QoL and loneliness), financial hardship, and social interactions in a large, representative sample of older adults from ELSA. In addition, we assessed whether the psychosocial impact of probable COVID-19 infection might vary across different sociodemographic groups. All outcomes were assessed before the pandemic began (i.e., 2018/2019) and on two occasions during the pandemic, which enabled us to test both short-term and longer-term associations. The data were collected online and by telephone interview to ensure coverage of those without internet access.     

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann–Whitney or Kruskal–Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53–62); 76% male; median HIV duration of infection, 18 years (15–29); nadir of CD4, 57/mmc (23–100) current CD4 count, 348/mmc (186–565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination.     

Effects of age and gender on neural correlates of emotion imagery

Mental imagery is part of people''s own internal processing and plays an important role in everyday life, cognition and pathology. The neural network supporting mental imagery is bottom‐up modulated by the imagery content. Here, we examined the complex associations of gender and age with the neural mechanisms underlying emotion imagery. We assessed the brain circuits involved in emotion mental imagery (vs. action imagery), controlled by a letter detection task on the same stimuli, chosen to ensure attention to the stimuli and to discourage imagery, in 91 men and women aged 14–65 years using fMRI. In women, compared with men, emotion imagery significantly increased activation within the right putamen, which is involved in emotional processing. Increasing age, significantly decreased mental imagery‐related activation in the left insula and cingulate cortex, areas involved in awareness of ones'' internal states, and it significantly decreased emotion verbs‐related activation in the left putamen, which is part of the limbic system. This finding suggests a top‐down mechanism by which gender and age, in interaction with bottom‐up effect of type of stimulus, or directly, can modulate the brain mechanisms underlying mental imagery.     

Pregnancy in uremic patients: an eventful journey

Renal damage, which can be caused by gestational anomalies such as pre-eclampsia, carries a risk of gestational complications; the greatest risk being in women who become pregnant while on hemodialysis or peritoneal dialysis. If this rare event occurs, there is a marked increase in the risk of pre-eclampsia, early uterine contractions and hydramnios, hypertensive crisis, preterm delivery and intrauterine growth retard. Furthermore, newborns are almost always of low birthweight. Patients who undergo renal transplantation are another high-risk category. In such cases, the pregnancy itself can compromise the success of the transplant and the immunosuppressive therapy correlated to it can become a threat to the course of the pregnancy and normal fetal growth. Therefore, in view of the lack of appropriate guidelines for the best possible approach to the treatment of women on dialysis or of those with a renal transplantation, it is best to advise these patients against becoming pregnant and/or to provide a valid counselling service illustrating the extreme difficulties and dangers involved in becoming pregnant.     

HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples

Background Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.Methods Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.Results We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.Conclusions We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.Subject terms: Diagnostic markers, Biliary tract cancer     

Supporting hemodynamics: what should we target? What treatments should we use?

Assessment and monitoring of hemodynamics is a cornerstone in critically ill patients as hemodynamic alteration may become life-threatening in a few minutes. Defining normal values in critically ill patients is not easy, because 'normality' is usually referred to healthy subjects at rest. Defining 'adequate' hemodynamics is easier, which embeds whatever pressure and flow set is sufficient to maintain the aerobic metabolism. We will refer to the unifying hypothesis proposed by Schrier several years ago. Accordingly, the alteration of three independent variables - heart (contractility and rate), vascular tone and intravascular volume - may lead to underfilling of the arterial tree, associated with reduced (as during myocardial infarction or hemorrhage) or expanded (sepsis or cirrhosis) plasma volume. The underfilling is sensed by the arterial baroreceptors, which activate primarily the sympathetic nervous system and renin-angiotensin-aldosterone system, as well as vasopressin, to restore the arterial filling by increasing the vascular tone and retaining sodium and water. Under 'normal' conditions, therefore, the homeostatic system is not activated and water/sodium excretion, heart rate and oxygen extraction are in the range found in normal subjects. When arterial underfilling occurs, the mechanisms are activated (sodium and water retention) - associated with low central venous oxygen saturation (ScvO₂) if underfilling is caused by low flow/hypovolemia, or with normal/high ScvO₂ if associated with high flow/hypervolemia. Although the correction of hemodynamics should be towards the correction of the independent determinants, the usual therapy performed is volume infusion. An accepted target is ScvO₂ >70%, although this ignores the arterial underfilling associated with volume expansion/high flow. For large-volume resuscitation the worst solution is normal saline solution (chloride load, strong ion difference = 0, acidosis). To avoid changes in acid-base equilibrium the strong ion difference of the infused solution should be equal to the baseline bicarbonate concentration.