Screening of anal cancer in HIV-infected MSM with anal cytology results in high rates of false positive results and elevated burden of high-resolution anoscopies. High-risk HPV up-regulates p16 and ...Ki67 expression in epithelial cells. We assessed the usefulness of P16/Ki-67 immunostaining cytology for the diagnosis of precancerous anal lesions.
Cross-sectional multicenter study. Concomitant anal liquid cytology with p16/Ki-67 immunostaining and HRA with biopsy of acetowhite lugol-negative lesions was performed in HIV-infected MSM. We compared the diagnostic performance of an abnormal anal cytology and p16/Ki-67 immunostaining relative to HRA-guided biopsy by logistic regression and comparison of ROC areas.
We included 328 HIV-infected MSM. HSIL was histologically diagnosed in 72 subjects (25.1%), and 2 (0.6%) were diagnosed with anal cancer. An abnormal cytology showed a sensitivity of 95.6% and a specificity of 58.8% for the diagnosis of biopsy-proven HSIL. P16/Ki67 positivity was associated with the presence of biopsy-proven HSIL (P trend = 0.004) but with low sensitivity (41.2%) and specificity (71%). The combination of standard cytology with P16/Ki67 immunostaining did not increment the predictive value of standard cytology alone (AUC 0.685 vs. 0.673, respectively, P = 0.688).
In HIV-infected MSM P16/Ki67 immunostaining does not improve the diagnostic accuracy of anal cytology, which shows a high sensitivity yet poor specificity. Other approaches aimed at improving the diagnostic accuracy of current techniques for the diagnostic of precancerous HSIL are warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plant–soil biodiversity interactions are fundamental for the functioning of terrestrial ecosystems. Yet, the existence of a set of globally distributed topsoil microbial and small invertebrate ...organisms consistently associated with land plants (i.e., their consistent soil‐borne microbiome), together with the environmental preferences and functional capabilities of these organisms, remains unknown. We conducted a standardized field survey under 150 species of land plants, including 58 species of bryophytes and 92 of vascular plants, across 124 locations from all continents. We found that, despite the immense biodiversity of soil organisms, the land plants evaluated only shared a small fraction (less than 1%) of all microbial and invertebrate taxa that were present across contrasting climatic and soil conditions and vegetation types. These consistent taxa were dominated by generalist decomposers and phagotrophs and their presence was positively correlated with the abundance of functional genes linked to mineralization. Finally, we showed that crossing environmental thresholds in aridity (aridity index of 0.65, i.e., the transition from mesic to dry ecosystems), soil pH (5.5; i.e., the transition from acidic to strongly acidic soils), and carbon (less than 2%, the lower limit of fertile soils) can result in drastic disruptions in the associations between land plants and soil organisms, with potential implications for the delivery of soil ecosystem processes under ongoing global environmental change.
We studied the soil organisms consistently associated with land plants (vascular plants and mosses) across contrasting climates, soils, and vegetation types. We found a small subset of bacteria, fungi, and protists that defined the consistent soil‐borne microbiome of land plants and determined their importance for the functioning of plant‐associated soils.
Introduction
Laparoscopic sleeve gastrectomy is one of the most common techniques in bariatric surgery, but there is no consensus on the optimal distance from the pylorus to start the gastric ...transection. The aim of this study is to determine the differences in gastric emptying, gastric distension and metabolic response between two starting distances.
Material and Methods
This is a prospective randomised study of 60 patients (30 patients with the section at 3 cm and 30 patients at 8 cm from the pylorus). We calculate at 6 and 12 months from surgery gastric emptying by scintigraphy (T1/2 min), gastric volume by CT scan (cc) and metabolic response by blood sample analysis (glucose, HbA1c, insulin, HOMA-IR, GLP-1, GIP and C-peptide).
Results
Gastric emptying increases the speed significantly in both groups but is greater in the 3-cm group (
p
< 0.05). Dividing groups into type 2 diabetic patients and non-diabetic patients, the speed in non-diabetic patients is significantly higher for the 3-cm group. Residual volume increases significantly in both groups, and there are no differences between them. One year after surgery, there are significant improvements in the hyperinsulinaemia in the patients of the 3-cm group with respect to the 8-cm group, but only in diabetic patients. No differences between groups are found regarding changes in GLP-1 or GIP.
Conclusions
Gastric emptying is faster in patients with antrum resection. The distance does not influence the gastric emptying of diabetic patients. Other mechanisms may explain metabolic response besides GLP-1 and its association with improvements in diabetes via gastric emptying.
Summary
Predictive tools for major bleeding (MB) using machine learning (ML) might be advantageous over traditional methods. We used data from the Registro Informatizado de Enfermedad TromboEmbólica ...(RIETE) to develop ML algorithms to identify patients with venous thromboembolism (VTE) at increased risk of MB during the first 3 months of anticoagulation. A total of 55 baseline variables were used as predictors. New data prospectively collected from the RIETE were used for further validation. The RIETE and VTE‐BLEED scores were used for comparisons. External validation was performed with the COMMAND‐VTE database. Learning was carried out with data from 49 587 patients, of whom 873 (1.8%) had MB. The best performing ML method was XGBoost. In the prospective validation cohort the sensitivity, specificity, positive predictive value and F1 score were: 33.2%, 93%, 10%, and 15.4% respectively. F1 value for the RIETE and VTE‐BLEED scores were 8.6% and 6.4% respectively. In the external validation cohort the metrics were 10.3%, 87.6%, 3.5% and 5.2% respectively. In that cohort, the F1 value for the RIETE score was 17.3% and for the VTE‐BLEED score 9.75%. The performance of the XGBoost algorithm was better than that from the RIETE and VTE‐BLEED scores only in the prospective validation cohort, but not in the external validation cohort.
Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ...ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non‐small‐cell lung cancer and melanoma patients. Cell‐free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA‐Q‐PCR or next‐generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty‐three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatment decisions, such as initiation of osimertinib treatment or selection of specific ALK tyrosine–kinase inhibitors. In conclusion, fluids close to metastatic sites are superior to blood for the detection of relevant mutations and can offer valuable clinical information, particularly in patients progressing to targeted therapies.
Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. Here, we present the results of prospective genetic testing of 42 cerebrospinal fluids, pleural effusions, and ascites, and we show that these fluids, which are closer to metastatic sites, are superior to plasma (P) for the detection of clinically relevant mutations.
Hidradenitis suppurativa (HS) is a chronic skin condition causing lesions in which high levels of interleukin (IL)-23 and T-helper 17 cells are found. Adalimumab remains the only approved treatment. ...Guselkumab, an antibody targeting the p19 protein subunit of extracellular IL-23, is approved for the treatment of moderate–severe psoriasis, but evidence on its efficacy in treating HS is limited.
To assess the effectiveness and safety of guselkumab in treating moderate–severe HS under clinical practice conditions.
A multicentre retrospective observational study was carried out in 13 Spanish Hospitals including adult HS patients treated with guselkumab within a compassionate use programme (March 2020–March 2022). Data referred to patient demographic and clinical characteristics at treatment initiation (baseline), patient-reported outcomes (Numerical Pain Rating Scale NPRS and Dermatology Life Quality Index DLQI), physician scores (International Hidradenitis Suppurativa Severity Score System IHS4, HS Physical Global Score HS-PGA and Hidradenitis Suppurativa Clinical Response HiSCR) were recorded at baseline and at 16, 24, and 48 weeks of treatment.
A total of 69 patients were included. Most (84.10%) had severe HS (Hurley III) and had been diagnosed for over ten years (58.80%). The patients had been subjected to multiple non-biological (mean 3.56) or biological (mean 1.78) therapies, and almost 90% of those treated with biologics had received adalimumab. A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores was observed from baseline to 48 weeks of guselkumab treatment (all p<0.01). HiSCR was achieved in 58.33% and 56.52% of the patients at 16 and 24 weeks, respectively. Overall, 16 patients discontinued treatment, mostly due to inefficacy (n=7) or loss of efficacy (n=3). No serious adverse events were observed.
Our results indicate that guselkumab may be a safe and effective therapeutic alternative for patients with severe HS that fail to respond to other biologics.
La hidradenitis supurativa (HS) es una situación cutánea crónica que causa lesiones en las que se encuentran altos niveles de interleucina (IL)-23 y células TH-17 colaboradoras, siendo adalimumab el único tratamiento aprobado. Guselkumab, un anticuerpo que focaliza la subunidad de la proteína p19 de IL-23 extracelular, ha sido aprobado para tratar la psoriasis de moderada a severa, siendo limitada la evidencia sobre su eficacia en el tratamiento de la HS.
Evaluar la efectividad y seguridad de guselkumab para el tratamiento de la HS de moderada a severa, en condiciones de práctica clínica.
Se llevó a cabo un estudio observacional retrospectivo y multicéntrico en 13 hospitales españoles, que incluyó pacientes adultos de HS tratados con guselkumab, dentro de un programa de uso compasivo (de marzo de 2020 a marzo de 2022). Se registraron al inicio y a las 16, 24 y 48 semanas de tratamiento los datos referentes a las características demográficas y clínicas de los pacientes, los resultados reportados por el paciente (Numerical Pain Rating Scale NPRS y Dermatology Life Quality Index DLQI), puntuaciones del facultativo (International Hidradenitis Suppurativa Severity Score System IHS4, HS Physical Global Score HS-PGA e Hidradenitis Suppurativa Clinical Response HiSCR).
Se incluyó un total de 69 pacientes, de los cuales la mayoría (84,10%) tenían HS severa (Hurley III) y habían sido diagnosticados hacía más de 10 años (58,80%). Dichos pacientes habían sido sometidos a múltiples terapias no biológicas (media 3,56) o biológicas (media 1,78), y casi el 90% de los tratados con biológicos habían recibido adalimumab. Se observó una reducción significativa de las puntuaciones IHS4, HS-PGA, NPRS y DLQI desde el inicio hasta las 48 semanas del tratamiento con guselkumab (total p<0,01). Se logró HiSCR en el 58,33% y el 56,52% de los pacientes, a las 16 y 24 semanas, respectivamente. A nivel global, 16 pacientes discontinuaron el tratamiento, en su mayoría debido a ineficacia (n=7) o pérdida de eficacia (n=3), no observándose episodios adversos graves.
Nuestros resultados indican que guselkumab puede ser una alternativa terapéutica segura y efectiva para los pacientes con HS severa que no responden a otros biológicos.
Aims
Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non‐massive PE, which may inform ...clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non‐massive PE during anticoagulation and after its discontinuation.
Methods and results
We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (<90 mm Hg). We compared the risks of recurrent VTE, major bleeding, and mortality using time‐to‐event multivariable competing risk modeling. There were 3.5% of massive PE among 38 996 patients with PE. During the anticoagulation period, massive PE was associated with a greater risk of major bleeding (subhazard ratio sHR 1.72, 95% confidence interval CI 1.28–2.32), but not of recurrent VTE (sHR 1.15, 95% CI 0.75–1.74) than non‐massive PE. An increased risk of mortality was only observed in the first month after PE. After discontinuation of anticoagulation, among 11 579 patients, massive PE and non‐massive PE had similar risks of mortality, bleeding, and recurrent VTE (sHR 0.85, 95% CI 0.51–1.40), but with different case fatality of recurrent PE (11.1% versus 2.4%, P = .03) and possibly different risk of recurrent fatal PE (sHR 3.65, 95% CI 0.82–16.24).
Conclusion
In this large prospective registry, the baseline hemodynamic status of the incident PE did not influence the risk of recurrent VTE, during and after the anticoagulation periods, but was possibly associated with recurrent PE of greater severity.
In order to monitor the evolution of the active layer in the South Shetland Islands, in February 2009 we established a new Circumpolar Active Layer Monitoring (CALM) site in the Limnopolar Lake basin ...on Byers Peninsula, Livingston Island. We monitored air, surface and ground (two boreholes of 135 and 80 cm deep) temperatures and Active Layer Thickness (ALT) was measured by mechanical probing in early February 2009, 2010 and 2011. The mean ALT was 44 cm with a range of about 92 cm, but where permafrost existed it was deeper than 1.0 m, as could be inferred from the borehole temperatures. ALT at this site was very dependent on air temperature and snow cover thickness, the ALT spatial distribution presenting the same pattern as soil penetration resistance, and higher values ALT coinciding with sites where patterned ground, ponds, and a near surface ground water saturation were observed. Additionally, ground temperature data provided an excellent tool for understanding the relationship between the ALT measured during the thaw season and the thermal evolution of the ground throughout the year.
The purpose of this study was to evaluate the consequences of bisphenol A (BPA) exposure in zebrafish (Danio rerio). Short-term effects at a testes level were assessed by means of different ...biomarkers in 60 male zebrafish exposed for 14 days in aquariums to different concentrations of BPA (1, 10, 100 and 1000 µg/l) in addition to a control batch. The LC-MS/MS method was used for the quantification of BPA. The BPA levels in the zebrafish tissues increased together with increasing exposure of fish to BPA. Several alterations were observed in the zebrafish testes. Particularly notable morphological changes included, a pronounced degeneration of all cell components, an increase in the percentage of the sustentacular (Sertoli) cells, and a marked decrease in the percentage of germ cells starting from concentrations of 100 µg/l of BPA. Our results indicate that histopathology and testes morphometry are sensitive biomarkers for the analysis of early effects of an environmental concentration of BPA in zebrafish experimental models. Our observations reveal that the nature and intensity of the morphological changes in the testes are concentration-dependent in the case of BPA, and manifest as adverse effects on the fish’s reproductive health.
Background
Organ donation continues to increase worldwide, but in general paediatric patients remain less likely to receive a transplant. The inclusion of neonates as donors after cDCD should be ...considered in an effort to increase donation rates.
Methods
The survey for a cross‐sectional national study of potential cDCD neonatal donors (Maastricht type III) was sent to all 90 level III Spanish neonatal units to explore: 1) protocols, education, and specific opinions on donation and 2) potential cDCD that could have been eligible over a 2‐year period (2014–2015).
Results
Forty‐five centers (50%) completed the survey, and 38/45 gave information about potential eligible donors. In 16% of the centers specific protocols on neonatal donation exist. All hospitals demanded more specific training, and 65% noted that the donation process could be a problem in the family's dismissal of the child.
During the study period 46 805 neonates were admitted in the 38 centers, and 625 neonates died. Ninety‐five born at a gestational age ≥34 weeks and above 2000 gr died after an EoL decision, 38 (40%) and 13 (14%) of them due to neonatal encephalopathy and multiple congenital anomalies, respectively. There were 31 (33%) elegible infants who died in less than 120 min due to pathologies that did not contraindicate donation.
Conclusions
Neonatal cDCD could help to reduce the gap between the supply of and demand for organs according to the potentially eligible patients emerging from this study. Training in EoL and donation processes should be provided to healthcare professionals.
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