COVID-19 pandemic on coronary artery and cerebrovascular diseases in Southern Spain: interrupted time series analysis.

OBJECTIVE: Healthcare systems have been put under intense pressure by the COVID-19 pandemic, although some studies have shown a decline in hospital admissions for cardiovascular and cerebrovascular diseases during the first and second wave of the pandemic. In addition, studies analyzing gender and procedural differences are scarce. The present study aimed to determine the impact of the pandemic on hospital admissions for acute myocardial infarction (AMI) and cerebrovascular disease (CVD) in Andalusia (Spain) and analyzed differences by gender and by percutaneous coronary interventions performed. PATIENTS AND METHODS: An interrupted time series analysis of AMI and CVD hospital admissions in Andalusia (Spain) was carried out to measure the impact of the COVID-19 outbreak. AMI and CVD cases admitted daily in public hospitals of Andalusia between January 2018 and December 2020 were included. RESULTS: During the pandemic, significant reductions in AMI [-19%; 95% confidence interval (CI): (-29%, -9%), p<0.001] and CVD [-17%; 95% CI: (-26%, -9%); p<0.01] in daily hospital admissions were observed. Differences were also produced according to the diagnosis (ST-Elevation Myocardial Infarction, Non-ST-Elevation Myocardial Infarction, other AMI and stroke), with a greater reduction in females for AMI and in males for CVD. Although there were more percutaneous coronary interventions during the pandemic, no significant reductions were observed. CONCLUSIONS: A decline in AMI and CVD daily hospital admissions during the first and second wave of COVID-19 pandemic was noted. Gender differences were observed, but no clear impact was observed in percutaneous interventions.

Poly(ADP-ribose) polymerase expression in kidney transplantation: from alfa (alpha) to Omega (Omega).

INTRODUCTION: Overactivation of the enzyme poly(ADP-ribose) polymerase (PARP-1) can be induced by ischemia-reperfusion and involved in the renal injury subsequent to kidney transplant. The poly(ADP-ribosy)lation mechanism alters free radical-induced DNA damage, which is repair by PARP-1 polymer. However, PARP-1 overexpression induces cellular necrosis. Our aim was to study the immunohistochemical PARP-1 expression in kidney transplant biopsies associated with various events. MATERIALS AND METHODS: We studied the nuclear expression of PARP-1 in kidney tubule cells by immunohistochemistry using the monoclonal antibody PAR01 in donor biopsies without acute tubular necrosis (ATN) (n = 60; controls), allografts that suffer ATN (n = 90) or an episode of acute humoral rejection (n = 12) or acute tubulointerstitial rejection (n = 25), or chronic allograft nephropathy (n = 25). Furthermore, we also studied protocol biopsies with subclinical rejection (n = 60). Renal lesions in transplant biopsies were graded blindly using 1997 Banff criteria without any clinical information. RESULTS: Biopsies without morphological features of ATN, namely acute tubulointerstitial rejection, borderline or subclinical rejection, showed lesser PARP-1 expression compared with biopsies with ATN or with ischemic mechanism of acute humoral rejection or chronic allograft nephropathys. We observed an inverse relation between PARP-1 expression and renal function (P < .001). Overall, renal biopsies showing ATN revealed greater expression of PARP-1 (r = 0.785, Pearson test). A significant relationship with PARP-1 expression was demonstrated with renal function (effective diuresis, serum creatinine levels) and pretransplant cold ischemia time (P < .001). CONCLUSION: Kidney transplant events including ischemia were associated with the highest PARP-1 expression and worse allograft renal function.

Role of poly-(ADP-ribose) polymerase in transplant acute tubular necrosis and its relationship with delayed renal function.

The enzyme poly(ADP-ribose) polymerase (PARP-1) participates in the repair of DNA damaged by genotoxic agents such as oxygen-derived free radicals. If the allograft suffers pretransplant cold ischemia and subsequent ischemia-reperfusion injury (IR), overactivation of PARP-1 can be induced, which may lead to an increase in acute tubular necrosis (ATN) and a delay in total recovery of renal function (RRF) of the transplanted organ. We studied the nuclear expression of PARP-1 in tubular cells by immunohistochemistry with the monoclonal antibody PAR01 in 104 kidney transplant biopsies from allografts with ATN. In 50% of biopsies with ATN, >50% of tubular nuclei were PARP-1+; only 9.6% of biopsies were negative. The increase in the immunohistochemical expression of PARP-1 showed a statistically significant relationship with the duration of cold ischemia, with serum creatinine levels, and with the time required to achieve effective diuresis (P < .0001, Spearman test). Cold ischemia of >24 hours and serum creatinine levels >1.7 mg/dL showed a statistically significant relationship with the highest PARP-1 expression levels (2.83 +/- 0.4 vs 1.36 +/- 0.8, P < .0001, Mann-Whitney U test). We conclude that PARP-1 plays an important role in ATN and RRF and is related to the extent and severity of ATN and to the renal allograft function.

Correlation of morphological findings with functional reserve in the aging donor: role of the poly (ADP-ribose) polymerase.

INTRODUCTION: The enzyme poly (ADP-ribose) polymerase (PARP-1) participates in the first events of DNA repair in higher organisms. Under conditions of tissue ischemia, this action can lead to significant decreases in NAD(+), massive adenosine triphosphate (ATP) depletion, and cell death. In renal grafts with pretransplantation cold ischemia and subsequent ischemia-reperfusion injury, overactivation of PARP-1 may lead to a higher index of acute tubular necrosis, a delay in total recovery of the function of the transplanted organ, and an early progression to chronic graft nephropathy. The present study examined whether increased tubular expression of PARP-1 in kidneys from aged donors contributed to recipient renal function. MATERIAL AND METHOD: We studied the nuclear expression of PARP-1 using immunohistochemistry with monoclonal antibody PAR01 in 75 kidney biopsy specimens from 40 aged donors. RESULTS: Immunohistochemical expression of PARP-1 showed a statistically significant relationship with donor age (r =.408, P =.006, Spearman test), with time required to achieve effective diuresis (r =.386, P =.01, Spearman test) and with creatinine levels in the first 3 months. We also highlighted a greater intensity of PARP-1 expression in suboptimal donor kidneys that failed to reduce the serum creatinine levels to <1.7 mg/dL (creatinine <1.7 PARP: 1.29 +/- 1.49 vs creatinine >1.7 PARP: 2.29 +/- 1.33, P =.047, Mann-Whitney U test). CONCLUSION: We conclude that the determination of PARP-1 in biopsy specimens from aged donors may be a useful predictive factor for renal graft function.

Lifestyles, environmental and phenotypic factors associated with lip cancer: a case-control study in southern Spain.

The aim of this study was to identify factors related to lip cancer (LC) considering individual characteristics and sociodemographic factors. A case-control study was carried out in the province of Granada (Andalusia, southern Spain). The cases were 105 males with squamous-cell carcinoma of the lip, diagnosed between 1987 and 1989 (aged 20-70 years) and identified by means of a population-based Cancer Registry. As controls, a randomised populational sample of 239 males, stratified by age, was used. Multiple logistic regression analysis showed that risk factors are lifetime cumulative tobacco consumption and alcohol consumption. An interaction was found between alcohol consumption and the smoking habit (leaving the cigarette on the lip): OR=23.6; 95% CI: 3.9-142.0. Other risk factors identified are clear eyes (OR=3.5; CI: 95% 1.5-8.0), sun exposure early in life and cumulative sun exposure during outdoor work (OR=11.9; 95%: CI: 1.3-108.9), and skin reaction to sun exposure (Fitzpatrick levels). Another interaction was found between skin reaction and a previous history of common sporadic warts (OR=4.4; 95% CI: 1.01-19.1). We conclude that LC is related to phenotype, skin reaction to sun exposure, cumulative and early sunlight exposure, and tobacco and alcohol consumption, as well as a low educational level. Leaving the cigarette on the lip is predictive of LC risk irrespective of cumulative tobacco consumption.

Liver fibrosis assessment with semiquantitative indexes and image analysis quantification in sustained-responder and non-responder interferon-treated patients with chronic hepatitis C.

BACKGROUND/AIMS: The effect of interferon on the reduction of liver fibrosis is controversial. We aimed to compare semiquantitative methods with a quantitative digital image analysis system to assess liver fibrosis in biopsies from patients with chronic hepatitis and different responses to interferon. METHODS: We studied 98 liver biopsies with chronic hepatitis C before and after recombinant interferon alfa-2 treatment, using conventional histological assessment, grading of histological activity, scoring/staging of fibrosis (Knodell and Scheuer), and quantification of fibrosis with image analysis (FibroQuant). RESULTS: Sustained-responders to interferon showed a significant reduction in histological lesions and in their Knodell and Scheuer activity indexes. The semiquantitative systems showed no reduction in fibrosis. The FibroQuant application showed a significant reduction in porto-periportal and septal areas among sustained-responders (P < 0.001) and non-responders (P < 0.05), and in porto-periportal and septal fibrosis areas only in sustained-responders (P < 0.001), whereas the percentage of fibrosis increased in non-responders (P < 0.001). CONCLUSIONS: The Scheuer system is useful for the daily evaluation of fibrosis, but the FibroQuant application provides more objective data on the anti-fibrogenic effects of interferon, which include a reduction in the porto-periportal area in sustained-responders and non-responders, accompanied by a reduction in the area of fibrosis only when the viral replication has ceased.

Automatic quantification of liver fibrosis: design and validation of a new image analysis method: comparison with semi-quantitative indexes of fibrosis.

BACKGROUND/AIMS: Liver fibrosis is one of the most important and characteristic histologic alterations in progressive and chronic liver diseases. Thus, in both clinical and experimental practice, it is fundamental to have a reliable and objective method for its precise quantification. Several semi-quantitative scoring systems have been described. All are time-consuming and produce partially subjective fibrosis evaluations that are not very precise. This paper describes the design and validation of an original image analysis-based application, FibroQuant, for automatically and rapidly quantifying perisinusoidal, perivenular and portal-periportal and septal fibrosis and portal-periportal and septal morphology in liver histologic specimens. METHODS: The implemented image-processing algorithms automatically segment interstitial fibrosis areas, while extraction of portal-periportal and septal region is carried out with an automatic algorithm and a simple interactive step. For validation, all automatically extracted areas were also manually segmented and quantified. RESULTS: Statistical analysis showed significant intra- and interoperator variability in manual segmentation of all areas. Automatic quantifications did not significantly differ from mean manual evaluations of the same areas. Comparison of our image analysis quantifications with staging histologic evaluations of liver fibrosis showed significant correlations (Spearman's, 0.72