Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent.

Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%, p < 0.01) and within the first 90 days of treatment (25.7% vs. 37.7%, p = 0.01). This negative association was confirmed by multivariable analysis. Higher mean steroid doses were observed among non-responders, and cumulative doses were inversely correlated with the disease control rate (DCR) around ICI initiation. Remarkably, poorer outcomes were observed even in patients belonging to the lowest dose quartile compared to the steroid-naïve population. The exposure to steroids after 6 months of ICI was not associated with worse survival outcomes. Our results suggest that the potential impact of steroids on ICI efficacy may be time-dependent, prevailing around ICI initiation, and dose-dependent, with modulation of neutrophil-to-lymphocyte ratio as a possible underlying mechanism.

A comprehensive, predictive mortality score for patients with bloodstream infections (PROBAC): a prospective, multicentre cohort study.

OBJECTIVES: Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort. METHODS: A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC. RESULTS: Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70 mmHg and PaO2/FiO2 ≤ 300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%-14% for 3-7 points, 26%-45% for 8-12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79-0.83) in the DC and 0.80 (0.78-0.83) in the VC. CONCLUSIONS: A 30 day mortality predictive score in BSI with good discrimination ability was developed and internally validated.

Microbiological diagnosis of pulmonary invasive aspergillosis in critically ill patients with severe SARS-CoV-2 pneumonia: a bronchoalveolar study.

BACKGROUND: Diagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD). METHODS: Prospective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose. RESULTS: Of the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%. CONCLUSIONS: Using a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA.

Burnout in nursing: A vision of gender and "invisible" unrecorded care.

AIM: To reflect on how characteristics inherent in the nursing profession might be related to burnout syndrome among the nursing collective. BACKGROUND: Most people are unaware of the tasks and responsibilities of the nursing profession, as well as the burnout rates suffered by nurses. The nursing profession is a feminized profession, and this feminization may lead to the assignment of gender stereotypes and roles traditionally attributed to women. Much of the care provided by nurses is unrecorded, "invisible" and could be seen as an extension of their role as caregivers. METHODS: This is a discussion paper. The literature on gender stereotypes, unrecorded (invisible) care in nursing and burnout are the argumentative basis of this work. DISCUSSION: Stereotypes and gender roles may explain the lack of recognition of some of the carework carried out by nurses. Care, which is the essence of the profession, continues to be largely invisible and is not valued. This lack of recognition of invisible care, coupled with gender stereotypes, may help to understand burnout syndrome in nursing. IMPACT FOR NURSING: Health organizations should take into account the history of the nursing profession and the stereotypes associated with it. It is necessary to recognize and make visible much of the care provided by nurses which are not recorded (invisible care), since this would facilitate the visibilization of the workload and could reduce the possibility of suffering burnout. If we want quality care and staff who enjoy the greatest possible well-being, it will be necessary to take these variables into consideration. One purpose should be: to care for them so that they can provide quality care to others. NO PATIENT OR PUBLIC CONTRIBUTION: This is a discussion paper.

Paternal alcohol consumption has intergenerational consequences in male offspring.

PURPOSE: Alcoholism is a heterogeneous set of disorders caused by ethanol intake. Harmful effects of paternal consumption on the offspring are poorly explored and not fully understood. We analyzed the effect of paternal alcohol consumption on both their own reproductive capacity and that of their male offspring. METHODS: We used a model of ethanol consumption (15% v/v in drinking water) for 12 days in adult CF-1 male mice. DNA integrity and post-translational modifications of histones were assessed in sperm; testicular weight, histology, and DNA fragmentation were analyzed. Treated or untreated male mice were mated with non-treated females to obtain two cell embryos that were cultured for 7 days; morphology and embryonic cell death were evaluated. Males of both groups were mated with non-treated females. Adult male offspring was euthanized, and sperm and testicular parameters determined. RESULTS: Paternal ethanol consumption caused histological and epigenetic changes, as well as damage in DNA integrity in the testicular germline and sperm. These alterations gave rise to deleterious effects on embryonic development and to testicular and spermatic changes in the offspring. CONCLUSION: This study provides critical information on reproductive disturbances brought about by paternal alcohol consumption and the profound impact these could have on the male progeny. The need to explore the effects of paternal alcohol consumption in detail and warn about the importance of controlling alcohol intake for the well-being of future generations should not be underscored.

Mathematical and statistical models for the control of mosquito-borne diseases: the experience of Costa Rica.

Objective: To summarize the results of research conducted in Costa Rica in which mathematical and statistical methods were implemented to study the transmission dynamics of mosquito-borne diseases. Methods: Three articles with mathematical and statistical analysis on vector-borne diseases in Costa Rica were selected and reviewed. These papers show the value and relevance of using different quantitative methods to understand disease dynamics and support decision-making. Results: The results of these investigations: 1) show the impact on dengue case reports when a second pathogen emerges, such as chikungunya; 2) recover key parameters in Zika dynamics using Bayesian inference; and 3) show the use of machine learning algorithms and climatic variables to forecast the dengue relative risk in five different locations. Conclusions: Mathematical and statistical modeling enables the description of mosquito-borne disease transmission dynamics, providing quantitative information to support prevention/control methods and resource allocation planning.

Her-2 Targeted Therapy in Advanced Urothelial Cancer: From Monoclonal Antibodies to Antibody-Drug Conjugates.

Metastatic urothelial cancer, associated with a poor prognosis, is still major cause of cancer-related death, with scarce options of effective treatment after progression to platinum-based chemotherapy and immunotherapy. The human epithelial growth factor receptor 2 (Her-2) has been identified as a new therapeutic target in medical oncology. However, despite the encouraging results in breast and gastric cancers, clinical trials with anti-Her-2 monoclonal antibodies and tyrosine-kinase inhibitors have shown limited efficacy of this strategy in urothelial tumors. Notably, more favorable data have been recently shown that antibody-drug conjugates are currently emerging as a novel promising approach for Her-2 targeted therapy in advanced urothelial cancer.

Receptor Tyrosine Kinase Inhibitors for the Treatment of Recurrent and Unresectable Bone Sarcomas.

Bone sarcomas are a heterogeneous group of rare tumors with a predominance in the young population. Few options of systemic treatment are available once they become unresectable and resistant to conventional chemotherapy. A better knowledge of the key role that tyrosine kinase receptors (VEGFR, RET, MET, AXL, PDGFR, KIT, FGFR, IGF-1R) may play in the pathogenesis of these tumors has led to the development of multi-target inhibitors (TKIs) that are progressively being incorporated into our therapeutic arsenal. Osteosarcoma (OS) is the most frequent primary bone tumor and several TKIs have demonstrated clinical benefit in phase II clinical trials (cabozantinib, regorafenib, apatinib, sorafenib, and lenvatinib). Although the development of TKIs for other primary bone tumors is less advanced, preclinical data and early trials have begun to show their potential benefit in advanced Ewing sarcoma (ES) and rarer bone tumors (chondrosarcoma, chordoma, giant cell tumor of bone, and undifferentiated pleomorphic sarcoma). Previous reviews have mainly provided information on TKIs for OS and ES. We aim to summarize the existing knowledge regarding the use of TKIs in all bone sarcomas including the most recent studies as well as the potential synergistic effects of their combination with other systemic therapies.

Evolution of Hydroxytyrosol, Hydroxytyrosol 4-ß-d-Glucoside, 3,4-Dihydroxyphenylglycol and Tyrosol in Olive Oil Solid Waste or "Alperujo".

The main by-product generated from the olive oil two-phase extraction system, or alperujo, is undoubtedly a rich source of bioactive components, among which phenolics are one of the most important. The evolution of four of its main phenolics: hydroxytyrosol (HT), hydroxytyrosol 4-ß-d-glucoside (Glu-HT), 3,4-dihydroxyphenylglycol (DHPG) and tyrosol (Ty) was studied over two seasons and in ten oil mills under similar climatological and agronomic conditions, for the first time using organic extraction and high-performance liquid chromatography (HPLC-DAD) determination. The results show that HT (200-1600 mg/kg of fresh alperujo) and Ty (10-570 mg/kg) increase, while DHPG (10-370 mg/kg) decreases only in the last month of the season and Glu-HT (1400-0 mg/kg) decreases drastically from the beginning. This evolution is similar between different seasons, with a high correlation between Glu-HT, HT, and Ty. On the other hand, it has been verified that a mixture of alperujos from all the oil mills, which is what the pomace extractor receives, is a viable source of a liquid fraction which is rich in the phenolics studied through organic extractions and especially after the application of a thermal treatment, obtaining values of 4.2 g/L of HT, 0.36 g/L of DHPG, and 0.49 g/L of Ty in the final concentrated liquid fraction.

Point-of-care lung ultrasound assessment for risk stratification and therapy guiding in COVID-19 patients: a prospective noninterventional study.

BACKGROUND: Lung ultrasound is feasible for assessing lung injury caused by coronavirus disease 2019 (COVID-19). However, the prognostic meaning and time-line changes of lung injury assessed by lung ultrasound in COVID-19 hospitalised patients are unknown. METHODS: Prospective cohort study designed to analyse prognostic value of lung ultrasound in COVID-19 patients by using a quantitative scale (lung ultrasound Zaragoza (LUZ)-score) during the first 72 h after admission. The primary end-point was in-hospital death and/or admission to the intensive care unit. Total length of hospital stay, increase of oxygen flow and escalation of medical treatment during the first 72 h were secondary end-points. RESULTS: 130 patients were included in the final analysis; mean±sd age was 56.7±13.5 years. Median (interquartile range) time from the beginning of symptoms to admission was 6 (4-9) days. Lung injury assessed by LUZ-score did not differ during the first 72 h (21 (16-26) points at admission versus 20 (16-27) points at 72 h; p=0.183). In univariable logistic regression analysis, estimated arterial oxygen tension/inspiratory oxygen fraction ratio (PAFI) (hazard ratio 0.99, 95% CI 0.98-0.99; p=0.027) and LUZ-score >22 points (5.45, 1.42-20.90; p=0.013) were predictors for the primary end-point. CONCLUSIONS: LUZ-score is an easy, simple and fast point-of-care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated by PAFI) to further refine risk stratification.

Unusual high 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) tracer deposition on a heart scintigraphy in a patient with AL amyloidosis: A case report.

We present a case of a 40-year-old Spanish man with cardiac amyloidosis in which a Tc-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-99m-DPD) scintigraphy was strongly suggestive of cardiac amyloidosis by transthyretin (ATTR) but endomyocardial biopsy (EB) analyzed by immunohistochemistry demonstrated a light chain amyloidosis (AL). Even though the Tc-99m-DPD has proven in different published papers that has high sensibility and specificity for differentiating AL and ATTR cardiac amyloidosis, we present an unusual case of an AL cardiac amyloidosis with a Perugini grade 3 on the scintigraphy. Diagnostic approach of cardiac amyloidosis following consensus documents is discussed to avoid diagnostic mistakes based on imaging techniques.

The threat of COVID-19 and its influence on nursing staff burnout.

AIMS: To evaluate whether the perceived threat of COVID-19 moderates the influence of work resources and demands on burnout. DESIGN: A cross-sectional study. METHODS: We used a convenience sample of 771 nurses working in 10 hospitals in northern Spain. The data on burnout, demand, and resources at work and the perceived threat of COVID-19 were compiled in the second fortnight of April 2020 using an online questionnaire. We used several hierarchical linear regression models. RESULTS: Work overload, material and human resources and social support at work were significant in explaining burnout. The perceived threat of COVID-19 variable was also significant and presented the highest regression coefficient (ß = 0.392). The perceived threat of COVID-19 moderated the relationship between social support at work and burnout. CONCLUSION: The perceived threat of COVID-19 helped to explain the degree of burnout in nurses and moderated the relationship between social support at work and burnout. IMPACT: Hospitals should implement strategies to ensure that health emergency situations are not perceived as a threat. In pandemics, the organization should maintain clear, fluid, and regular communication with the nursing staff, which would help increase staff members' confidence and sense of control.

Retrospective case review of combined local mepivacaine and steroid injections into vaginal trigger points for the management of moderate-to-severe perineal pain after childbirth.

OBJECTIVE: After an obstetric trauma, a non-negligible number of postpartum women complain of perineal pain and dyspareunia. These symptoms clearly diminish their quality of life. Many treatment options have been suggested, such as oral analgesia, local anaesthetic, or steroid injections… Regretfully, none of these have yet demonstrated their efficacy with the validated trials. The objective of this review is to retrospectively evaluate the response to vaginal infiltrations into the trigger points (where the vaginal/perineal examination sets off the maximum intensity of pain) combining local anaesthetic and corticosteroids. METHODS: Our goal is to detect women who complain of sexual disfunction and perineal pain 2 and 6 months after childbirth. All reviewed cases correspond to vaginal deliveries made between June 2016 and April 2017. Trigger points were detected through a vaginal examination. Patients with moderate-to-severe perineal pain were determined using a visual analogue score (VAS 0-10). We suggested a treatment of vaginal infiltration specifically into the trigger points. Patients underwent local injections with a combination of mepivacaine hydrochloride 2% (8 ml) and betamethasone acetate (2 ml). RESULTS: Twenty-seven women were treated with vaginal injections directly into the trigger points. Seven of them [7/27 (25.92%)] were treated 2 months after delivery and experienced complete recovery of their perineal pain 4 months after the treatment. Those who first chose conservative treatment [20/27 (74.08%)] were also assessed 6 months after giving birth. This group continued to suffer the same symptoms and they then subsequently underwent vaginal injections. As well as the first group, these women experienced complete recovery of their perineal pain after treatment. No side effects have been registered so far. CONCLUSION: Women treated with vaginal injection into the trigger points improved in a fast and effective way. It seems to be a well-tolerated and safe option for women with moderate-to-severe pain.

Murine sperm capacitation, oocyte penetration and decondensation following moderate alcohol intake.

Male chronic alcohol abuse causes testicular failure and infertility. We analyzed the effects of moderate sub-chronic alcohol intake on sperm morphology, capacitation, fertilization and sperm head decondensation. CF-1 male mice were administered 15% ethanol in drinking water for 15 days; control mice received ethanol-free water. Similar patterns of tyrosine phosphorylation were observed in capacitated spermatozoa of control and treated males. Percentage of hyperactivation (H) and spontaneous (SAR) and progesterone-induced (IAR) acrosome reaction significantly decreased at 120 and 150 min of capacitation in treated males compared to controls (H: 14.1 ± 2.5 vs 23.7 ± 2.6, P < 0.05; SAR-T120 min: 17.9 ± 2.5 vs 32.9 ± 4.1, P < 0.01; IAR-150 min: 43.3 ± 3.5 vs 73.1 ± 1.1, P < 0.001, n = 6). During in vitro fertilization (2.5, 3.5 and 4.5 h post-insemination), there was an increased percentage of fertilized oocytes (with a decondensed sperm head and one or two pronuclei) in treated males (P < 0.001, n = 7). After 60 min of in vitro decondensation with glutathione plus heparin, the percentage of decondensed sperm heads was significantly higher in treated males than in controls (mean ± s.d.: 57.1 ± 5.6 vs 48.3 ± 4.5, P < 0.05, n = 5). The percentage of morphologically normal sperm heads was significantly decreased in treated males with respect to controls (P < 0.001, n = 9). These results show that short-term moderate alcohol consumption in outbred mice affect sperm morphology, hyperactivation, acrosomal exocytosis, and the dynamics of in vitro fertilization and in vitro sperm nuclear decondensation.

Antiarrhythmic effect linked to melatonin cardiorenal protection involves AT1 reduction and Hsp70-VDR increase.

Lethal ventricular arrhythmias increase in patients with chronic kidney disease that suffer an acute coronary event. Chronic kidney disease induces myocardial remodeling, oxidative stress, and arrhythmogenesis. A manifestation of the relationship between kidney and heart is the concomitant reduction in vitamin D receptor (VDR) and the increase in angiotensin II receptor type 1 (AT1 ). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase in the heat shock protein 70 (Hsp70)-an antioxidant factor. We aim to determine the mechanisms involved in melatonin (Mel) prevention of kidney damage and arrhythmogenic heart remodeling. Unilateral ureteral-obstruction (UUO) and sham-operated rats were treated with either melatonin (4 mg/kg/day) or vehicle for 15 days. Hearts and kidneys from obstructed rats showed a reduction in VDR and Hsp70. Associated with AT1 up-regulation in the kidneys and the heart of UUO rats also increased oxidative stress, fibrosis, apoptosis, mitochondrial edema, and dilated crests. Melatonin prevented these changes and ventricular fibrillation during reperfusion. The action potential lengthened and hyperpolarized in melatonin-treated rats throughout the experiment. We conclude that melatonin prevents renal damage and arrhythmogenic myocardial remodeling during unilateral ureteral obstruction due to a decrease in oxidative stress/fibrosis/apoptosis associated with AT1 reduction and Hsp70-VDR increase.

Phytochemical Study of the Genus Salpichroa (Solanaceae), Chemotaxonomic Considerations, and Biological Evaluation in Prostate and Breast Cancer Cells.

Twelve Salpichroa taxa have been phytochemically analyzed. From the aerial parts of S. scandens, four known salpichrolides A, C, I, S, and an unreported withanolide named salpichrolide V (1), were isolated. In S. dependens, S. gayi, S. glandulosa subsp. glandulosa, S. glandulosa subps. weddellii, S. leucantha, S. micrantha, S. microloba, S. proboscidea, S. ramosissima, S. tristis var. tristis, and S. weberbauerii, no withanolides were found. The chemical content of ca. 85% of the Salpichroa taxa is in agreement with molecular studies, which suggest that Salpichroa and Jaborosa, a genus considered morphologically close to Salpichroa, are distant in the systematic of the Solanoideae subfamily. Moreover, the in vitro cytotoxic activity of a set of natural salpichrolides and derivatives was examined against two prostate carcinoma cell lines (PC3 and LNCaP) and two human breast cancer cell lines (MCF-7 and T47D). Several compounds showed moderate activity (IC50  = 64.91 - 29.97 µm).

Association of oral breathing with dental malocclusions and general health in children.

BACKGROUND: The aims of this study were to analyze the association of oral breathing with dental malocclusions and aspects of general health such as acute illnesses, oxygen saturation in blood and its possible implication in the process of nutrition. METHODS: A prevalence analytic study was carried out. Five dentists explored to children between 6 and 12 years and measured their oxygen saturation. Parents completed a questionnaire of 11 items about general health (colds, ear infections, tonsillitis and taking antibiotics) and the food preferences of their children. At the end, children were classified in oral breathing group (prevalence cases) or nasal breathing group (controls). RESULTS: There were statistical differences between cases (452 children) and controls (752 children) in the facial morphometric measurements. Oral breathing children had statistically less percentage of oxygen saturation than controls (92.3±3.3% versus 96.5±2.3%), took less time to have lunch and preferred less consistent and sugary food. Cases had had more prevalence of pathologies in the last year and of taking the antibiotics. This group also had higher prevalence of allergies compared with controls group (P<0.001). CONCLUSIONS: Oral breathing is significantly associated with specific dental malocclusions and important aspects of general health such as oxygen saturation and the nutrition. On the same line, oral breathing is related to a significantly higher prevalence of allergies and a significantly more likely getting sick and taking medication.

Changes in renal WT-1 expression preceding hypertension development.

BACKGROUND: Hypertension is a public health problem with mostly unknown causes, and where strong hereditary genetic alterations have not been fully elucidated. However, the use of experimental models has provided valuable information. Recent evidences suggest that alterations in key nephrogenic factors, such as Wilms' tumor 1 transcription factor (WT-1), could contribute to the development of hypertension. The aim of this paper is to evaluate the expression of WT-1 and related genes in the nephrogenic process in connection with the development of hypertension as well as the corresponding anatomical and functional correlation. METHODS: Male spontaneously hypertensive and control rats were evaluated weekly from birth until week 8 of life. Their blood pressure was taken weekly using the tail-cuff blood pressure system. Weekly, 5 rats per group were sacrificed with a lethal injection of pentobarbital, and their kidneys were removed, decapsulated and weighed. The serum was collected for measuring biochemical parameters. The results were assessed using one-way analysis of variance for comparisons between groups. RESULTS: The relationship between renal weight/total body weights was established, without significantly different values. These data were compared with apoptosis, fibrosis, number and size of the glomeruli. The elevation of systolic blood pressure was significant since week 6. Biochemical values differed slightly. Histology showed a slight increase in deposits of collagen fibers since week 4. Additionally, in kidney cortices, the expression of WT-1, heat shock protein 70 (Hsp70) and vitamin D receptors (VDR) decreased since week 4. Finally, we demonstrated ultrastructural damage to mitochondria since week 4. CONCLUSIONS: Our results would suggest an unprecedented link, possibly a regulatory mechanism, between WT-1 on nephrogenic alteration processes and their relationship with hypertension. Moreover, and previous to the increase in blood pressure, we demonstrated low expressions of WT-1, VDR and Hsp70 in kidneys from neonatal SHRs. If so, this may suggest that deregulation in the expression of WT-1 and its impact on nephrogenesis induction could be crucial in understanding the development and maintenance of hypertension.

Inhalation analgesia with nitrous oxide versus other analgesic techniques in hysteroscopic polypectomy: a pilot study.

STUDY OBJECTIVE: To show the decrease in pain and better tolerance to inhalation analgesia with a 50% equimolar mixture of nitrogen protoxide and oxygen in hysteroscopic polypectomy compared with paracervical anesthesia and a control group. DESIGN: One hundred six patients scheduled for office hysteroscopy and polypectomy were divided into the following 3 groups: the control group, the nitrous oxide group, and the paracervical infiltration group. Patients were assigned sequentially (Canadian Task Force classification II-1). SETTING: The study took place in a hysteroscopy outpatient clinic under the supervision of a gynecologist and 2 nurses trained to cooperate in the trial. PATIENTS: One hundred six women from Area III of Madrid Community, Spain, who had been diagnosed with endometrial polyps at a gynecology office and were scheduled for office hysteroscopy and polypectomy agreed to participate in the study. INTERVENTIONS: Patients in group 1 (control group) received no treatment. Group 2 received inhaled nitrous oxide and group 3 paracervical infiltration with 1% lidocaine. MEASUREMENTS AND MAIN RESULTS: Pain was assessed using the visual analog scale (0-10). Pain perceived by patients was lower in the nitrous Oxide group (mean: 3.55 ± 0.60, median: 3) versus the control group (mean: 5.49 ± 1.88, median: 6, p < .05) and the paracervical infiltration group (mean: 4.22 ± 1.73, median: 5). Tolerance to pain, assessed by the medical staff using qualitative variables, was bad for the control group, very good for the nitrous oxide group, and good for the paracervical infiltration group (p < .05). There were no complications in 82% of the patients in the nitrous oxide group, whereas in the paracervical infiltration group, there were complications in more than 50% of the patients. No severe complications occurred. CONCLUSION: Nitrous oxide is a safe and effective analgesic technique for polipectomy office hysteroscopy compared with the paracervical infiltration and control groups.