Antibiotics for exacerbations of asthma.

BACKGROUND: Asthma is a chronic respiratory condition that affects over 300 million adults and children worldwide. It is characterised by wheeze, cough, chest tightness, and shortness of breath. Symptoms typically are intermittent and may worsen over a short time, leading to an exacerbation. Asthma exacerbations can be serious, leading to hospitalisation or even death in rare cases. Exacerbations may be treated by increasing an individual's usual medication and providing additional medication, such as oral steroids. Although antibiotics are sometimes included in the treatment regimen, bacterial infections are thought to be responsible for only a minority of exacerbations, and current guidance states that antibiotics should be reserved for cases in which clear signs, symptoms, or laboratory test results are suggestive of bacterial infection. OBJECTIVES: To determine the efficacy and safety of antibiotics in the treatment of asthma exacerbations. SEARCH METHODS: We searched the Cochrane Airways Trials Register, which contains records compiled from multiple electronic and handsearched resources. We also searched trial registries and reference lists of primary studies. We conducted the most recent search in October 2017. SELECTION CRITERIA: We included studies comparing antibiotic therapy for asthma exacerbations in adults or children versus placebo or usual care not involving an antibiotic. We allowed studies including any type of antibiotic, any dose, and any duration, providing the aim was to treat the exacerbation. We included parallel studies of any duration conducted in any setting and planned to include cluster trials. We excluded cross-over trials. We included studies reported as full-text articles, those published as abstracts only, and unpublished data. DATA COLLECTION AND ANALYSIS: At least two review authors screened the search results for eligible studies. We extracted outcome data, assessed risk of bias in duplicate, and resolved discrepancies by involving another review author. We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs), and continuous data as mean differences (MDs), all with a fixed-effect model. We described skewed data narratively. We graded the results and presented evidence in 'Summary of findings' tables for each comparison. Primary outcomes were intensive care unit/high dependence unit (ICU/HDU) admission, duration of symptoms/exacerbations, and all adverse events. Seconday outcomes were mortality, length of hospital admission, relapse after index presentation, and peak expiratory flow rate (PEFR). MAIN RESULTS: Six studies met our inclusion criteria and included a total of 681 adults and children with exacerbations of asthma. Mean age in the three studies in adults ranged from 36.2 to 41.2 years. The three studies in children applied varied inclusion criteria, ranging from one to 18 years of age. Five studies explicitly excluded participants with obvious signs and symptoms of bacterial infection (i.e. those clearly meeting current guidance to receive antibiotics). Four studies investigated macrolide antibiotics, and two studies investigated penicillin (amoxicillin and ampicillin) antibiotics; both studies using penicillin were conducted over 35 years ago. Five studies compared antibiotics versus placebo, and one was open-label. Study follow-up ranged from one to twelve weeks. Trials were of varied methodological quality, and we were able to perform only limited meta-analysis.None of the included trials reported ICU/HDU admission, although one participant in the placebo group of a study including children with status asthmaticus experienced a respiratory arrest and was ventilated. Four studies reported asthma symptoms, but we were able to combine results for only two macrolide studies of 416 participants; the MD in diary card symptom score was -0.34 (95% confidence interval (CI) -0.60 to -0.08), with lower scores (on a 7 point scale) denoting improved symptoms. Two macrolide studies reported symptom-free days. One study of 255 adults authors reported the percentage of symptom-free days at 10 days as 16% in the antibiotic group and 8% in the placebo group. In a further study of 40 children study authors reported significantly more symptom-free days at all time points in the antibiotic group compared with the usual care group. The same study reported the duration in days of the index asthma exacerbation, again favouring the antibiotic group. One study of a penicillin including 69 participants reported asthma symptoms at hospital discharge; the between-group difference for both studies was reported as non-significant.We combined data for serious adverse events from three studies involving 502 participants, but events were rare; the three trials reported only 10 events: five in the antibiotic group and five in the placebo group. We combined data for all adverse events (AEs) from three studies, but the effect estimate is imprecise (OR 0.99, 95% CI 0.69 to 1.43). No deaths were reported in any of the included studies.Two studies investigating penicillins reported admission duration; neither study reported a between-group difference. In one study (263 participants) of macrolides, two participants in each arm were reported as experiencing a relapse, defined as a further exacerbation, by the six-week time points. We combined PEFR endpoint results at 10 days for two macrolide studies; the result favoured antibiotics over placebo (MD 23.42 L/min, 95% CI 5.23 to 41.60). One study in children reported the maximum peak flow recorded during the follow-up period, favouring the clarithromycin group, but the confidence interval includes no difference (MD 38.80, 95% CI -11.19 to 88.79).Grading of outcomes ranged from moderate to very low quality, with quality of outcomes downgraded for suspicion of publication bias, indirectness, imprecision, and poor methodological quality of studies. AUTHORS' CONCLUSIONS: We found limited evidence that antibiotics given at the time of an asthma exacerbation may improve symptoms and PEFR at follow-up compared with standard care or placebo. However, findings were inconsistent across the six heterogeneous studies included, two of the studies were conducted over 30 years ago and most of the participants included in this review were recruited from emergency departments, limiting the applicability of findings to this population. Therefore we have limited confidence in the results. We found insufficient evidence about several patient-important outcomes (e.g. hospital admission) to form conclusions. We were unable to rule out a difference between groups in terms of all adverse events, but serious adverse events were rare

One-Step Laparoscopic Management of a Female Adnexal Tumor of Wolffian Origin

We report a case of female adnexal tumor of Wolffian origin (FATWO), a rare neoplasm arising from the mesonephric ducts. A 48-year-old woman came first to our center for a recent discovery of a pelvic mass. Transvaginal ultrasonographic findings suggested a solid right para-ovarian mass suspected to be malignant. After thorough counseling, the patient underwent operative laparoscopy for excision of the para-ovarian mass with frozen section (FS) examination resulting in the diagnosis of a poorly differentiated adenocarcinoma. In this case, FS results allowed performing a comprehensive oncological staging, through a totally laparoscopic extrafascial hysterectomy, bilateral adnexectomy, total omentectomy, pelvic wall peritonectomy, and pelvic, parasacral and para-aortic lymphadenectomy. Final pathological and immunohistochemical results confirmed the diagnosis of FATWO. To our knowledge, this is the first case of FATWO managed entirely by a minimally invasive laparoscopic approach in a single surgical session

Endometriosis in the time of internet: how web navigation affects women with endometriosis

Objectives: Patients often search for health-related information on the internet allthough this trend may have some benefits, it also has some risks, such as misinformation. The aim of this study is to evaluate how Internet information seeking affect the level of anxiety in patients with endometriosis. Materials and methods: This prospective observational study was conducted at our outpatient clinic between March 2019 and December 2020. We enrolled We enrolled all patients with a confirmed sonographic diagnosis of endometriosis who had sought information about the disease prior to our visit. We divided them into two groups based on the source of information (Internet only vs multiple sources). Before the visit, we asked women to fill-in validated questionnaires about anxiety, such as the Generalized Anxiety Disorder-7 (GAD) and the Spielberg State Trait Anxiety Inventory (STAI- Y6) and the Endometriosis Health Profile (EHP) − 5. After the visit, the STAI-Y6 was resubmitted to each woman. Results: We enrolled 200 women who filled-in the questionnaires: 46 reported the Internet as the only source of information, 52 sought information also from medically qualified sources, 74 consulted only healthcare professionals, and 28 resorted to medical journals. Women who used the Internet as their exclusive source of information were younger on average and their STAI-Y6 score after the visit was significantly lower compared to other group (34.1 ± 11.5 vs 42.1 ± 14.7, p =.001). Moreover, the difference between the STAI-Y6 scores before and after our assessment was higher in these women (-18.3 ± 14.7 vs −10.3 ± 16.5, p =.003). Conclusions: Women who sought information online were younger, had lower levels of state trait anxiety after our medical evaluation, and a had a greater reduction in anxiety levels after our examination compared to women who consulted other sources to learn more about endometriosis.KEY MESSAGES Women using only Internet are younger than those who use other sources of information. Women who researched symptoms online showed higher pre-examination anxiety levels. Patients with severe pain symptoms consulted both the internet and professionals

Comparison of perioperative outcomes between standard laparoscopic and robot-assisted approach in patients with rectosigmoid endometriosis

Introduction: Robot-assisted laparoscopic surgery (RALS) has gained widespread application in several surgical specialties. Previous studies on the feasibility and safety of RALS vs standard laparoscopy (S-LPS) for rectosigmoid endometriosis are limited and reported conflicting data. This study aims to compare S-LPS and RALS in patients with rectosigmoid endometriosis in terms of perioperative surgical and clinical data. Material and methods: This is a multicentric, observational, prospective cohort study including 44 patients affected by rectosigmoid endometriosis referred to two tertiary referral centers for endometriosis from September 2018 to September 2019. Patients were divided into two groups: 22 patients underwent S-LPS, and 22 underwent RALS. Our primary outcome was to compare operative time (from skin incision to suture) between the two groups. Secondary outcomes included: operative room time (patient entry into operative room and patient out), estimated blood loss, laparotomic conversion rate, length of hospital stay, perioperative complications, and evaluation of endometriosis-related symptoms at 12-month follow up. Results: The two groups were comparable regarding preoperative and surgical data, except for higher rates of hysterectomies and bilateral uterosacral ligament removal procedures in the RALS group. Also after adjusting for these discrepancies, operative time was similar between S-LPS and RALS. Operative room time was statistically longer in the RALS group compared with that of S-LPS. No statistically significant difference was found concerning other study outcomes. Pain and bowel symptoms improved in both groups at 12-month follow up. Conclusions: If performed by expert teams, RALS provides similar perioperative outcomes compared with S-LPS in rectosigmoid endometriosis surgical treatment, except for longer operative room time

Exercise training improves erectile dysfunction (ED) in patients with metabolic syndrome on phosphodiesterase-5 (PDE-5) inhibitors

Introduction. Erectile dysfunction (ED) affects about 50% of males aged 40-70 years old. ED shares with atherosclerotic disease several common risk factors; therefore, it may be considered a surrogate marker of atherosclerosis. Sincephosphodiesterase-5 inhibitors are well known pharmacologic agents capable of significant improvement in ED, we designed this study to evaluate whether exercise training is of added value in patients with ED who are already on PDE-5 inhibitors. Methods. We recruited 20 male patients affected by ED with metabolic syndrome.At baseline, all patients underwent Cardio-Pulmonary Exercise Testing (CPET) and the International Index of Erectile Function (IIEF) test.After the initial evaluation, patients were subdivided into two groups: tadalafil group (group T, n=10), who were maintained only on tadalafil therapy, and a tadalafil/exercise training group (T/E group, n=10)who continued tadalafil but in addition underwent a2-month structured exercise training program. Results. Basal anthropometric characteristics of study population showed no significant differences. Although bothgroups showed at 2 months an improvement of the IIEF score, thiswas more evident in the T/E group (T group: 11.2 vs 14.2, P=0.02; T/E group: 10.8 vs 20.1, P<0.001). There was an improvement of oxygen consumption at peak exercise (VO2peak) only in the T/E group patients (T group: 13.63±2.03 vs 14.24±2.98 mL/kg/min; P=0.521; T/E group: 13.41±2.97 vs 16.58±3.17 mL/kg/min; P=0.006). A significant correlation was found between the changes in VO2peak and the modifications in IIEF score (r=0.575; P=0.001). Conclusion. Exercise training in ED patients treated with PDE-5 inhibitors is of added valuesincefurther improves ED, as evaluated by IIEF score, and increases functional capacity

Dienogest alone or dienogest combined with estrogens in the treatment of ovarian endometriomas, that is the question. A retrospective cohort study

Purpose: to compare the effects of Dienogest 2 mg (D) alone or combined with estrogens (D + ethinylestradiol 0.03 mg, D + EE; D + estradiol valerate 1-3 mg, D + EV) in terms of symptoms and endometriotic lesions variations. Methods: This retrospective study included symptomatic patients in reproductive age with ultrasound diagnosis of ovarian endometriomas. Medical therapy for at least 12 months with D, D + EE or D + EV was required. Women were evaluated at baseline visit (V1) and after 6 (V2) and 12 months (V3) of therapy. Results: 297 patients were enrolled (156 in the D group, 58 in the D + EE group, 83 in the D + EV group). Medical treatment leaded to a significant reduction in size of endometriomas after 12 months, with no differences between the three groups. When comparing D and D + EE/D + EV groups, a significant decrease of dysmenorrhea was detected in the D group than in D + EE/D + EV group. Conversely, the reduction of dysuria was more significative in the D + EE/D + EV groups rather than in the D group. Regarding tolerability, treatment associated side effects were reported by 16.2% patients. The most frequent one was uterine bleeding/spotting, significantly higher in the D + EV group. Conclusion: Dienogest alone or associated with estrogens (EE/EV) seems to be equally effective in reducing endometriotic lesions mean diameter. The reduction of dysmenorrhea was more significative when D was administered alone, while dysuria seems to improve more when D is associated with estrogens

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.

BACKGROUND: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. PATIENTS AND METHODS: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. RESULTS: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. CONCLUSIONS: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study

Purpose To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. Methods Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. Results Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22–4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23–3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23–3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49–79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69–38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38–22.09). Conclusion Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. Trial registration Clinical trial registration number: NCT03354793

Multi-ancestry genome-wide association study of asthma exacerbations

Altres ajuts: European Regional Development Fund "ERDF A way of making Europe"; Allergopharma-EAACI award 2021; SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020; Sandler Family Foundation; American Asthma Foundation; RWJF Amos Medical Faculty Development Program; National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, R01HL141845); National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844); National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, R56MD013312); National Institute of General Medical Sciences (NIGMS) (RL5GM118984); Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030); National Human Genome Research Institute (NHGRI) (U01HG009080); GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences; Slovenian Research Agency (P3-0067); SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (C3330-16-500106); NHS Research Scotland; Wellcome Trust Biomedical Resource (099177/Z/12/Z); Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII (AC15/00015); UK Medical Research Council and Wellcome (102215/2/13/2); University of Bristol; Swedish Heart-Lung Foundation, Swedish Research Council; Region Stockholm (ALF project and database maintenance); NHS Chair of Pharmacogenetics via the UK Department of Health; Innovative Medicines Initiative (IMI) (115010); European Federation of Pharmaceutical Industries and Associations (EFPIA); Spanish National Cancer Research Centre; Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17); Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); U.S. National Institutes of Health (HL07966); European Social Fund "ESF Investing in your future"; Ministerio de Ciencia, Innovación y Universidades; Universidad de La Laguna (ULL); European Academy of Allergy and Clinical Immunology (EAACI); European Respiratory Society (ERS) (LTRF202101-00861); Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012); Singapore Ministry of Education Academic Research Fund; Singapore Immunology Network (SIgN); National Medical Research Council (NMRC Singapore); Biomedical Research Council (BMRC Singapore); Agency for Science Technology and Research (A*STAR Singapore, N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, H17/01/a0/008); Sime Darby Technology Centre; First Resources Ltd; Genting Plantation; Olam International; U.S. National Institutes of Health (HL138098).Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR) = 0.82, p = 9.05 × 10 and replication: OR = 0.89, p = 5.35 × 10) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR = 0.85, p = 3.10 × 10 and replication: OR = 0.89, p = 1.30 × 10). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense