The psychological impact of COVID-19 among primary care physicians in the province of Verona, Italy: a cross-sectional study during the first pandemic wave.

BACKGROUND: Among healthcare professionals working with COVID-19 patients, general practitioners (GPs) are under considerable pressure and may develop adverse mental health outcomes. OBJECTIVES: To assess mental health outcomes on GPs working during the COVID-19 pandemic and to explore their associations with personal characteristics and features of GP practices. METHODS: Observational cross-sectional study conducted on a sample of GPs working in Verona province (Italy) during the first pandemic wave. Participants were invited to complete a web-based form addressing socio-demographic and work-related information, previous practice organization, practice re-organization during the COVID-19 pandemic, and a set of measures for post-traumatic stress (IES-R), anxiety (SAS), depression (PHQ-9), and burnout (MBI-GS). RESULTS: A total of 215 GPs (38.3% of the eligible population) participated. Overall, 44.7% reported COVID-19-related traumatic events; among these, 35.9% (95% CI, 26%‒46%) developed symptoms of post-traumatic distress. Furthermore, 36% (95% CI, 29%‒43%) reported symptoms of anxiety, 17.9% (95% CI, 12%‒23%) symptoms of at least moderate depression, and 25.4% (95% CI, 19%‒32%) symptoms of burnout. Multivariate regressions showed that being quarantined or admitted for COVID-19 was associated with all the mental health outcomes considered. Being female, working in rural settings, and having less professional experience were associated with higher anxiety and depression. The ability to diagnose COVID-19 increased self-perceived professional efficacy, thus contributing to burnout reduction. CONCLUSION: The high prevalence of adverse mental health outcomes among GPs during the pandemic highlights the importance of timely interventions in this population and promoting targeted preventive actions in the event of future healthcare crises.

A Preliminary Case-Control Study: Peritoneal Approach in Congestive Heart Failure Treatment.

BACKGROUND: Congestive heart failure (CHF) associated with worsening renal function is a very common disorder, and, as well known, the goal of the treatment is reducing venous congestion and maintaining a targeted extracellular volume. The objective of the study is to evaluate regular peritoneal ultrafiltration treatment compared to a standard conservative approach in NYHA III-IV CHF patients. In particular, the primary endpoints of the study were the major event-free survival and the total days of medical care per month (which consist of the days of hospitalization and the number of outpatient visits). MATERIAL AND METHODS: This is a retrospective case-control study. Twenty-four patients were included in the present study. Twelve consecutive patients were treated with peritoneal treatment (group A) and 12 matched for age, gender, and severity of disease with a standard approach. Patients were observed over a maximum period of 18 months. Information on events, hospitalizations, and number of visits was collected during follow-up. RESULTS: During the follow-up, we observed a major event in 4 patients in group A (33.3%) and in 8 patients in group B (66.7%). In group B, we observed 7 deaths and 1 ICD shock, while in group A, 3 deaths and 1 ICD shock. The number of visits per month was significantly lower in patients treated with the peritoneal method (1.2 [0.4-4.1] vs. 2.5 [2.0-3.1]; p = 0.03). The total days of medical care was significantly lower in group A (2.0 [1.1-5.5] vs. 4.4 [3.0-8.7]; p = 0.034). A multiple event analysis according to the Andersen-Gill model showed a significant event-free survival for group A. During the follow-up, we did not observe any episode of peritonitis in the treated group. CONCLUSIONS: Our study shows that the peritoneal technique is a good therapeutic tool in well-selected patients with CHF. In accordance with prior experience, this intervention has not only an important and significant clinical impact but also potential economic and social consequences.

Specific heparanase inhibition reverses glucose-induced mesothelial-to-mesenchymal transition.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells induced by high glucose (HG) levels is a major biological mechanism leading to myofibroblast accumulation in the omentum of patients on peritoneal dialysis (PD). Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate chains, is involved in the EMT of several cell lines, and may have a major role in this pro-fibrotic process potentially responsible for the failure of dialysis. Its specific inhibition may therefore plausibly minimize this pathological condition. METHODS: An in vitro study employing several biomolecular strategies was conducted to assess the role of HPSE in the HG-induced mesothelial EMT process, and to measure the effects of its specific inhibition by SST0001, a N-acetylated glycol-split heparin with a strong anti-HPSE activity. Rat mesothelial cells were grown for 6 days in HG (200 mM) culture medium with or without SST0001. Then EMT markers (VIM, α-SMA, TGF-ß) and vascular endothelial growth factor (VEGF) (a factor involved in neoangiogenesis) were measured by real-time PCR and immunofluorescence/western blotting. As a functional analysis, trans-epithelial resistance (TER) and permeability to albumin were also measured in our in vitro model using a Millicell-ERS ohmmeter and a spectrophotometer, respectively. RESULTS: Our results showed that 200 mM of glucose induced a significant gene and protein up-regulation of VEGF and all EMT markers after 6 days of culture. Intriguingly, adding SST0001 on day 3 reversed these biological and cellular effects. HPSE inhibition also restored the normal TER and permeability lost during the HG treatment. CONCLUSION: Taken together, our data confirm that HG can induce EMT of mesothelial cells, and that HPSE plays a central part in this process. Our findings also suggest that pharmacological HPSE inhibition could prove a valuable therapeutic tool for minimizing fibrosis and avoiding a rapid decline in the efficacy of dialysis in patients on PD, though clinical studies and/or trials would be needed to confirm the clinical utility of this treatment.

How has peritoneal dialysis changed over the last 30 years: experience of the Verona dialysis center.

BACKGROUND: The last decade has witnessed considerable improvement in dialysis technology and changes in clinical management of patients in peritoneal dialysis (PD) with a significant impact on long term clinical outcomes. However, the identification of factors involved in this process is still not complete. METHODS: Therefore, to assess this objective, we retrospectively analyzed clinical records of 260 adult patients who started PD treatment from 1983 to 2012 in our renal unit. For the analysis, we divided them into three groups according to the time of starting dialysis: GROUP A (n: 62, 1983-1992), GROUP B (n: 66, 1993-2002) and GROUP C (n: 132, 2003 to 2012). RESULTS: Statistical analysis revealed that patients included in the GROUP C showed a reduction in mean patients' age (p = 0.03), smoking habit (p = 0.001), mean systolic blood pressure (p < 0.0001) and an increment in hemoglobin levels (p < 0.0001) and residual diuresis (p = 0.016) compared to the other two study groups. Additionally, patients included in GROUP C, mainly treated with automated peritoneal dialysis, showed a reduced risk of all-causes mortality and a decreased risk to develop acute myocardial infarction and cerebrovascular disease. Patients' age, diabetes mellitus and smoking habit were all positively associated with a significant increased risk of mortality in our PD patients, while serum albumin levels and residual diuresis were negatively correlated. CONCLUSIONS: Therefore, the present study, revealed that in the last decade there has been a growth of our PD program with a concomitant modification of our patients' characteristics. These changes, together with the evident technical advances, have caused a significant improvement of patients' survival and a decrement of the rate of hospitalization. Moreover, it reveals that our pre-dialysis care, modifying the above-mentioned factors, has been a major cause of these clinical improvements.

[Omentopexy in Peritoneal Catheter Malfunction].

Among the various problems associated with peritoneal dialysis, besides infectious causes, the risk of catheter malfunction plays a significant role in conditioning the continuation of the method, accounting for up to 15-18% of the total causes of dialysis drop-out. When non-invasive maneuvers, such as the use of laxatives to stimulate intestinal peristalsis or heparin and/or urokinase have no effect, videolaparoscopy is the only method that directly detects the precise causes of peritoneal catheter malfunction. Those found are, with decreasing frequency, the winding of the catheter between the intestinal loops and the omentum (wrapping), the dislocation of the catheter, the combination of wrapping and dislocation, the occlusion of the catheter by a fibrin plug, the adhesions between the intestine and abdominal wall, the occlusion of the catheter by epiploic appendages or adnexal tissue and, occasionally, the presence of a new formation of endoperitoneal tissue enveloping and obstructing the peritoneal catheter. We report the case of a young patient of African ethnicity who, only five days after catheter placement, experienced malfunction. A videolaparoscopy revealed wrapping with invagination of omental tissue inside the catheter. After omental debridement, a proper peritoneal cavity washout with heparin was resumed, and after a couple of weeks, APD was initiated. About a month later, a new malfunction without signs of coprostasis or problems with the abdominal radiogram was observed. However, a subsequent catheterography confirmed the blockage of drainage. This was followed by another catheterography and omentopexy, with definitive solution of the Tenckhoff malfunction.

[Post-renal transplant pregnancy: a project to plan carefully]. / Gravidanza post-trapianto: un progetto da pianificare.

Kidney transplant is the best treatment for end-stage renal disease (ESRD) as it improves the quality of life and reduces the mortality risk for most patients compared with maintenance dialysis. Additionally, evidence from the literature suggests that renal function, endocrine status and libido rapidly improve after kidney transplant, and one in 50 women of childbearing age become pregnant. Therefore, it seems clear that pregnancy after transplant is a great challenge for physicians involved in this field. The available information on pregnancy outcomes is largely derived from case reports and single-center series, which are unlikely to be representative. Moreover, poor results are less likely to be reported. Many of the reports on long-term outcome show the results of past medical, obstetric, and neonatal care, which may be very different from current practice. Attempts are being made to provide more up-to-date, representative data through national transplantation pregnancy registries. A great number of researchers worldwide have analyzed the biological and endocrinological machinery associated with this event. Additionally, several strategies have been introduced to avoid unplanned pregnancies and to minimize maternal and fetal complications in renal transplant recipients. It seems evident that the return to fertility soon after transplant is often associated with unplanned pregnancy, which can expose both mother and fetus to considerable risks. This underpins the necessity to recommend contraceptive counseling and start clinical follow-up in order to early identify possible pregnancy-related risk factors. In general, pregnancy should not be recommended within the first year after kidney transplant because the risk of acute rejection is greatest and immunosuppressive therapy the most aggressive. It should be planned when organ function and immunosuppressive therapy are stabilized and there is no sign of rejection, hypertension, or chronic infection. Additionally, renal transplant patients and their physicians together must try to identify the best timing, carry out pre-pregnancy screening, and delineate clinical follow-up and future pharmacological programs to minimize or avoid serious maternal and fetal complications. Finally, additional studies are needed to better understand the physiology associated with this condition, improve the pharmacological approach, and analyze the complex ethical and social implications of this important aspect of renal transplantation.

Analysis of the 3'UTR of the prostaglandin synthetase-2 (PTGS-2/COX-2) gene in non-melanoma skin cancer after organ transplantation.

To define the potential involvement of polymorphisms in the 3'untranslated region (3'UTR) of the prostaglandin synthetase-2 (PTGS-2) gene to non-melanoma skin cancer (NMSC) predisposition after transplantation, we screened for genetic variant, relevant parts of this region. It contains binding sites for trans-acting factors, an alternative polyadenylation site and putative target sequences for miRNAs. Variant +8473T>C did not appear to play a functional role in the regulation of gene expression in human keratinocyte-transfected cells. In addition to the well-known +8473T>C, we identified four polymorphisms: +8293G>C, +10259T>G, +10267G>A and +10335G>A. No allele frequency differences were observed between cases and controls neither for +8473T>C nor for any of the identified polymorphisms, suggesting that polymorphisms in the 3'UTR of the PTGS2 gene are rare and unlikely to represent risk factor for NMSC after transplantation.

Incidence and clinical predictors of primary opportunistic deep cutaneous mycoses in solid organ transplant recipients: a multicenter cohort study.

BACKGROUND: Primary opportunistic deep cutaneous fungal infections may cause significant morbidity and mortality in solid organ transplant recipients (OTR), but no data exist about their incidence, timing, and clinical predictors in a long-term follow-up. PATIENTS AND METHODS: A series of 3293 consecutive OTR including 1991 kidney, 929 heart, and 373 liver transplant recipients were enrolled. Patients were regularly followed up since time at transplantation (mean 5.5 yr +/-5.9 SD) and primary opportunistic fungal infections registered. Persons-year at risk (PYs), incidence rates (IR), incidence rate ratios (IRR), and 95% confidence intervals were computed. RESULTS: Twenty-two cases of deep cutaneous mycoses were detected, (IR 1.2 cases per 1000 PYs) after a mean follow-up time since transplantation of 2.5 yr +/- 2.0 SD (median 1.8 yr). Six patients had subsequent systemic involvement and three patients died of systemic dissemination. A higher risk for mycoses was observed in the first two yr after transplantation, (IRR 35.9, p < 0.0001), in renal transplant recipients (IRR 5.1 p = 0.030), and in patients transplanted after the age of 50 (IRR 11.5 p = 0.020). CONCLUSIONS: Primary deep cutaneous opportunistic mycoses in OTR occur mainly in the first two yr after transplantation, in renal transplant recipients, and in older patients.

[A case of AL amyloidosis with fulminant evolution].

Amyloidosis represents a heterogeneous group of pathologies characterized by the deposit, in the form of fibrils, in the various organs and tissues of the body, of abnormal proteins; the deposits made up of these fibrils are called amyloid or amyloid substance. AL amyloidosis, also called "light chains", is a primary form characterized by deposits of light chains of monoclonal immunoglobulins, proteins that are produced by the bone marrow with the aim of protecting the body from pathological processes; for unknown reasons, these immunoglobulins, once fulfilled their function, do not dissolve but, on the contrary, they transform into amyloid fibrils and accumulate progressively, transported by the bloodstream, in the various organs and tissues. Below we report the case of a 77-year-old Caucasian male patient hospitalized at our Operative Unit for nephrotic syndrome and creatinine increase in the last couple of months, compared to previous normal tests. The patient underwent a renal biopsy and a bone marrow smear with evidence of AL amyloidosis (or primary amyloidosis) and of the presence, at serum immunofixation, of small IgG multiple myeloma k. Treated with bortezomib (1 mg/m 2 ) and soldesam (10 mg) first and with lenalidomid after, the patient had a clinical course burdened by symptomatic hypotension, due to severe dysautonomia. He had to start replacement treatment with haemodiafiltration for terminal kidney disease two months after the onset of illness. He died 4 months after the first hospitalization for nephrotic syndrome.

The impact of pruritus on the quality of life of patients undergoing dialysis: a single centre cohort study.

BACKGROUND: Pruritus is common in dialysis patients, but no studies have addressed its impact on the patients' quality of life (QoL). OBJECTIVE: We sought to measure the impact of pruritus on the QoL of patients undergoing chronic hemodialysis (HHD) or peritoneal dialysis (PPD). METHODS: Pruritus intensity was measured on a 10-point visual analog scale. QoL was investigated with the 36-item Short Form of the Medical Outcomes Study questionnaire (SSF-336), the 12-item General Health Questionnaire (GHQ-12) and a dermatological questionnaire (Skindex-29). RESULTS: One hundred and thirty-nine patients on HD and 30 on PD were recruited. Pruritus was found in 88/169 patients (52.1%),with no differences between HD and PD patients. Prevalence of poor sleep in patients with pruritus was higher than in those without (559% vs. 11%; p<0.001). Both physical and mental scores of SF-36 did not correlate with the presence and the intensity of pruritus. Pruritus intensity was significantly related to poor scores in all 3 subscales of Skindex-29 (symptoms, social function and emotions). In the subscales of social function and emotions, worse scores were observed in patients undergoing HD and with minor psychiatric disorders (GHQpos). CONCLUSIONS: Pruritus had a high level of impact on all aspects of QoL and was a predictor of poor sleep. Type of dialysis and minor psychiatric disorders affect the emotional and social aspects of QoL.

[Late recovery of renal function in a patient with acute on chronic renal failure treated with peritoneal dialysis]. / Tardivo recupero della funzione renale in un paziente con insufficienza renale acuta su cronica trattato con dialisi peritoneale.

Contrast-induced nephropathy has become a significant source of hospital morbidity and mortality particularly in patients with multi-organs defects. No current treatment can reverse or ameliorate contrast induced nephropathy once it occurs, but prophylaxis is possible. We present the case of a 61-year-old male patient with concomitant chronic kidney disease (CKD stage III K/DOQI) and diabetes complicated by severe multi-vascular disease, who developed acute kidney damage probably due to the simultaneously exposure to intravascular contrast media and cholesterol crystal embolism. In addition, owing to rapid deterioration of renal function, this patient started renal replacement therapy. No renal biopsy was performed due to the poor clinical condition of the patient. After a month of hemodialysis, he switched to a peritoneal dialysis procedure to which specific treatment for vascular lesions, including antibiotics, prostanoids, hyperbaric oxygen therapy, antiaggregants/anticoagulants and physiotherapy, was associated. After 7 months, the dialysis treatment was stopped and he began intensive clinical follow-up. At present, the patient is in conservative medical treatment (the Tenckhoff catheter has been removed), he is in good condition and severe vascular lesions are absent. Our conclusion is that contrast-induced nephropathy in vasculopathic diabetic patients requires a multidisciplinary approach. In particular, good cooperation between nephrologists and angiologists is useful to avoid rapid and chronic deterioration of renal failure and to prevent the onset and development of severe vascular damage.

Downregulation of nuclear-encoded genes of oxidative metabolism in dialyzed chronic kidney disease patients.

BACKGROUND: Mitochondria, essential eukaryotic cells organelles defined as the "powerhouse of the cell" because of their ability to produce the vast majority of energy necessary for cellular metabolism, may have a primary role in the oxidative stress-related intracellular machinery associated to chronic kidney disease (CKD). METHODS: To better assess this research assumption, we decided to study the key factors regulating mitochondrial oxidative metabolism in CKD patients in peritoneal dialysis (PD, n = 15) using several bio-molecular methodologies. RESULTS: RT-PCR experiments demonstrate that the expression level of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear respiratory factor-1 (NRF-1), two genes primarily involved in mitochondrial biogenesis and functions, were significantly hypo-expressed in peripheral blood mononuclear cells of PD patients compared to healthy subjects (HS, n = 15). Additionally, mRNA levels of several PGC1-α downstream target genes (TFAM, COX6C,COX7C, UQCRH and MCAD) were profoundly down-regulated in PD cells. TFAM protein analysis confirmed gene-expression results. High plasmatic concentration of Malondialdehyde found in PD patients, confirmed the contribution of the oxidative stress to these biological effects. Finally, Nuclear factor erythroid-derived 2-like 2 (NRF2 or NFE2L2), a transcription factor for numerous antioxidant/detoxifying enzymes and one of its target genes, superoxide dismutase-2 mitochondrial (SOD2) were up-regulated in PD compared to HS. CONCLUSIONS: Our results revealed, for the first time, that CKD-PD patients' PBMC, through a complex intracellular biochemical machinery, are able to modulate their mitochondrial functions probably in the attempt to reduce oxidative metabolic damage and to turn on a valuable defense cellular strategy against oxidative stress.

Incidence and clinical predictors of a subsequent nonmelanoma skin cancer in solid organ transplant recipients with a first nonmelanoma skin cancer: a multicenter cohort study.

OBJECTIVE: To compare the long-term risk of primary nonmelanoma skin cancer (NMSC) and the risk of subsequent NMSC in kidney and heart transplant recipients. DESIGN: Partially retrospective cohort study. SETTING: Two Italian transplantation centers. PATIENTS: The study included 1934 patients: 1476 renal transplant recipients and 458 heart transplant recipients. MAIN OUTCOME MEASURES: Cumulative incidences and risk factors of the first and subsequent NMSCs. RESULTS: Two hundred patients developed a first NMSC after a median follow-up of 6.8 years after transplantation. The 3-year risk of the primary NMSC was 2.1%. Of the 200 patients with a primary NMSC, 91 (45.5%) had a second NMSC after a median follow-up after the first NMSC of 1.4 years (range, 3 months to 10 years). The 3-year risk of a second NMSC was 32.2%, and it was 49 times higher than that in patients with no previous NMSC. In a Cox proportional hazards regression model, age older than 50 years at the time of transplantation and male sex were significantly related to the first NMSC. Occurrence of the subsequent NMSC was not related to any risk factor considered, including sex, age at transplantation, type of transplanted organ, type of immunosuppressive therapy, histologic type of the first NMSC, and time since diagnosis of the first NMSC. Histologic type of the first NMSC strongly predicted the type of the subsequent NMSC. CONCLUSIONS: Development of a first NMSC confers a high risk of a subsequent NMSC in transplant recipients. Intensive long-term dermatologic follow-up of these patients is advisable.

Glutathione S-transferase and CYP1A1 gene polymorphisms and non-melanoma skin cancer risk in Italian transplanted patients.

Solid organ transplant recipients are at higher risk of non-melanoma skin cancer (NMSC), especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Genetic alterations in the production of detoxifying enzymes such as glutathione S-transferase (GST) and CYP1A1 may enhance this risk. We investigated the frequency of GST genotypes (GSTM1, GSTM3, GSTT1 and GSTP1) and CYP1A1 in 239 transplant recipients: 107 cases with NMSC and 132 controls free from NMSC matched for type of transplanted organ, duration of transplantation, sex and age. Allele GSTP1*A was associated with a higher risk of NMSC [odds ratio (OR) 1.7 (1.1-2.5); P = 0.017]. Homozygosity for allele GSTP1 Val(105) was lower in cases [OR 0.3 (0.1-0.8); P = 0.012], especially in patients with SCC [OR 0.1 (0.0-0.7); P = 0.012]. A higher risk of BCC was found in patients with GSTM1 null/null [null/null versus A + B, OR 3.1 (1.4-6.8); P = 0.003]. Analysis of allelism and interaction between allelic variants showed significant association between combined GSTM1 and CYP1A1 Val(462) genotypes, where individuals homozygous for the risk allele GSTM1 null and carrying also the allele CYP1A1 Val(462), show a higher risk of developing NMSC [OR 4.5 (1.1-21.4); P = 0.03], especially SCC [OR 6.5 (1.4-34.4); P = 0.01]. GSTP1 polymorphisms are associated with both BCC and SCC risk. GSTM1 polymorphisms seem to be involved in BCC risk, while GSTM1 null/null genotype combined with CYP1A1 allele Val(462) are associated with a higher risk for SCC, indicating that allelism and/or interactions between allelic variants at other loci may also influence the risk of NMSC, particularly SCC.

Nutrición y el riñón: cómo manejar a los pacientes con falla renal

Se cree que la nutición desempeña un papel fundamental en el manejo de la falla renal crónica y aguda. Hay un cúmulo de evidencia que sugiere que las dietas sin restricción de proteinas aceleran el progreso de la falla renal crónica. Por consiguiente, se han desarrollado varias recomendaciones en el sentido de limitar la cantidad y calidad de la ingesta de nitrógeno con el propósito de frenar el avance del paciente hacia un estado de dependencia de la dialisis. La falla renal aguda plantea unos desafíos diferentes en vista de que suele estar asociada con estados hipermetabólicos. Con respecto, a la administración de sustratos de nitrogeno, tal parece que las formulaciones combinadas de aminoácidos esenciales y no esenciales son tan eficaces como las formulaciones a base de aminoácidos esenciales únicamente.