The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05), and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01) and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005) compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03). In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

ATRA increased the number of ciliated cells in HT and LT.

<p>(<b>A</b>) Immunofluorescence of omentum-derived mesothelial cells (control) and effluent-derived mesothelial cells from LT and HT grown until confluence in the presence of ATRA (0, 50, 100 and 200 nM). Cells were labeled with anti-acetylated α-tubulin (green). Nuclei were labeled with ToPro-3 (blue). HT and LT cultures exhibited a reduction in the number of ciliated cells (e and i, respectively). ATRA increased the number of ciliated cells in LT (f, g and h) and HT (j, k and l), being more notable in HT. In control, ATRA decreased the number of ciliated cells. Panel k shows the zoom of a cell with two cilia. (B to E) Quantification of number of ciliated cells. Mean ± SEM of three individual experiments from three different patients are shown. (<b>B</b>) *<i>P<0</i>.<i>05</i> versus control; <i>***P<0.001</i> versus control. (<b>C</b>) <i>**P<0.01</i> and <i>**P<0.01</i> versus control with ATRA 0 nM. (<b>D</b>) <i>**P<0.01</i> and <i>*P<0.05</i> versus LT with ATRA 0 nM. (<b>E</b>) <i>*P<0.05</i> and <i>**P<0.01</i> versus HT with ATRA 0 nM. ATRA, all trans retinoic acid; LT, low transporter; HT, high transporter.</p

ATRA decreased α-SMA expression in LT and HT cultures.

<p>(<b>A</b>) Immunofluorescence of omentum-derived mesothelial cells (control) and effluent-derived mesothelial cells from LT and HT grown until confluence in the presence of ATRA (0, 50 and 100 nM). Cells were labeled with anti-α-SMA (red). Nuclei were labeled with ToPro-3 (blue). LT and HT cultures were positive for α-SMA staining (d and g). (<b>B</b> and <b>C</b>) Western blot analyses for α-SMA in total cell lysates of mesothelial cells treated as in A. α-SMA expression was importantly augmented in LT cultures. ATRA decreased α-SMA content in LT and in HT cultures. Mean ± SEM of three individual experiments from three different patients are shown. (<b>C</b>) ***<i>P<0.001</i> versus control; ***<i>P<0.001</i> versus HT; <i>*P<0.05</i> and <i>***P<0.001</i> versus LT with ATRA 0 nM; <i>*P<0.05</i> versus HT with ATRA 0 nM. ATRA, all trans retinoic acid; α-SMA, α-smooth muscle actin; LT, low transporter; HT, high transporter.</p

ATRA improved vimentin organization and decreased its expression.

<p>(<b>A</b>) Immunofluorescence of omentum-derived mesothelial cells (control) and effluent-derived mesothelial cells from LT and HT grown until confluence in the presence of ATRA (0, 50 and 100 nM). Cells were labeled with anti-vimentin (red). In LT cultures (d), vimentin immunofluorescence was more intense and exhibited elongated fibers (arrows). These fibers were also observed in HT cultures (g, arrows). ATRA improved vimentin organization in LT and HT, being more notable in LT (f). (<b>B</b> and <b>C</b>) Western blot analyses for vimentin in total cell lysates of mesothelial cells treated as in A. Vimentin expression was augmented in LT and HT cultures. ATRA reduced the vimentin content in LT and HT. Mean ± SEM of three individual experiments from three different patients are shown. **<i>P<0.01</i> versus control; <i>*P<0.05</i> versus LT with ATRA 100 nM and <i>**P<0.01</i> versus HT with ATRA 100 nM. ATRA, all trans retinoic acid; LT, low transporter; HT, high transporter.</p

Retinoic acid improved cell morphology and decreased the number of hypertrophic cells in LT cultures.

<p>(<b>A</b>) Omentum-derived mesothelial cells (control) and effluent-derived mesothelial cells from LT and HT grown until confluence in the presence of ATRA (0, 50, 100 and 200 nM). LT cells exhibited an increase in their average size (e, arrowheads) and hypertrophy (e, double asterisk). In HT cultures epithelial (i, arrowheads) and hypertrophic (i, double asterisk) cells were both observed. ATRA reduced the presence of hypertrophic cells in LT, in a concentration-dependent manner (f, g and h). (B to E) Quantification of total (empty bars), hypertrophic (hatched bars) and flattened (filled bars) in mesothelial cells treated as in A. LT and HT exhibited less cells by field and more hypertrophic cells than control cultures (<b>B</b>). In LT cultures, ATRA decreased the number of hypertrophic cells (<b>D</b>). Scanning electron microscopy, x300, bar= 50µm. Representative photomicrographs were obtained by duplicate from three different patients. Mean ± SEM are shown. (<b>B</b>) <i>***P< 0.001</i> and <i>*P<0.05</i> versus control total cells;<i>**P<0.01</i> versus control hypertrophic cells. (<b>C</b>)<i>**P<0.01</i> versus control flattened cells with ATRA 0 nM (<b>D</b>) <i>**P<0.01</i> and <i>*P<0.05</i> versus LT with ATRA 0nM; <i>**P<0.01</i> and <i>***P<0.001</i> versus LT with ATRA 0 nM. ATRA, all trans retinoic acid; LT, low transporter; HT, high transporter.</p