Ribonucleoprotein Assembly Defects Correlate with Spinal Muscular Atrophy Severity and Preferentially Affect a Subset of Spliceosomal snRNPs

Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival motor neuron (SMN) protein. SMN together with Gemins2-8 and unrip proteins form a macromolecular complex that functions in the assembly of small nuclear ribonucleoproteins (snRNPs) of both the major and the minor splicing pathways. It is not known whether the levels of spliceosomal snRNPs are decreased in SMA. Here we analyzed the consequence of SMN deficiency on snRNP metabolism in the spinal cord of mouse models of SMA with differing phenotypic severities. We demonstrate that the expression of a subset of Gemin proteins and snRNP assembly activity are dramatically reduced in the spinal cord of severe SMA mice. Comparative analysis of different tissues highlights a similar decrease in SMN levels and a strong impairment of snRNP assembly in tissues of severe SMA mice, although the defect appears smaller in kidney than in neural tissue. We further show that the extent of reduction in both Gemin proteins expression and snRNP assembly activity in the spinal cord of SMA mice correlates with disease severity. Remarkably, defective SMN complex function in snRNP assembly causes a significant decrease in the levels of a subset of snRNPs and preferentially affects the accumulation of U11 snRNP—a component of the minor spliceosome—in tissues of severe SMA mice. Thus, impairment of a ubiquitous function of SMN changes the snRNP profile of SMA tissues by unevenly altering the normal proportion of endogenous snRNPs. These findings are consistent with the hypothesis that SMN deficiency affects the splicing machinery and in particular the minor splicing pathway of a rare class of introns in SMA

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

hypertension in patients with acute pulmonary embolism

Introduction: Pulmonary hypertension (PH) is the most important prognostic factor after acute pulmonary embolism (PE). Therefore, determination of patients who will develop PH after acute PE is crucial. The aim of the present study was to evaluate the predictive value of the CHADS2 and CHA2DS2-VASc scores for PH in patients with acute PE.Material and methods: Seventy-nine adults who presented with acute PE, had an admission systolic pulmonary artery pressure (sPAP) measured on echocardiogram and no previous history of PE, were retrospectively identified from the computerized database. 31 patients who had sPAP 40 mm Hg were categorized as a "PH" group.Results: SPAP was > 40 mm Hg in 48 patients (60.8%), with a mean sPAP of 60.9 +/- 16.1 mm Hg (median = 60, min-max = 41-100 mm Hg). In multivariate logistic regression models adjusted for CHADS2 and CHA2DS2-VASc score components, only age was found to be related with the development of PH. SPAP was weakly positively correlated with CHADS2 (p = 0.047; r = 0.224) and CHA2DS2-VASc (p = 0.023; r = 0.256) scores. SPAP values were increasing with the severity of the scores.Conclusions: Both CHADS2 and CHA2DS2-VASc scores could be useful in the determination of which patients should be closely followed up in order to prevent the development of PH after acute PE.C1 [Yilmaz, Samet; Yaylali, Yalin Tolga; Kuyumcu, Mevlut Serdar; Senol, Hande] Pamukkale Univ Hosp, Pamukkale Denizli, Turkey.[Unal, Sefa; Tufekcioglu, Omac] Hlth Sci Univ, Bilkent City Hosp, Ankara, Turkey

Relationship between CHA2DS2-VASc and CHADS2 scores with pulmonary hypertension in patients with acute pulmonary embolism.

INTRODUCTION: Pulmonary hypertension (PH) is the most important prognostic factor after acute pulmonary embolism (PE). Therefore, determination of patients who will develop PH after acute PE is crucial. The aim of the present study was to evaluate the predictive value of the CHADS2 and CHA2DS2-VASc scores for PH in patients with acute PE. MATERIAL AND METHODS: Seventy-nine adults who presented with acute PE, had an admission systolic pulmonary artery pressure (sPAP) measured on echocardiogram and no previous history of PE, were retrospectively identified from the computerized database. 31 patients who had sPAP ≤ 40 mm Hg were categorized as a "normal pulmonary pressure" group, whereas 48 patients who had sPAP > 40 mm Hg were categorized as a "PH" group. RESULTS: SPAP was > 40 mm Hg in 48 patients (60.8%), with a mean sPAP of 60.9 ± 16.1 mm Hg (median = 60, min-max = 41-100 mm Hg). In multivariate logistic regression models adjusted for CHADS2 and CHA2DS2-VASc score components, only age was found to be related with the development of PH. SPAP was weakly positively correlated with CHADS2 (p = 0.047; r = 0.224) and CHA2DS2-VASc (p = 0.023; r = 0.256) scores. SPAP values were increasing with the severity of the scores. CONCLUSIONS: Both CHADS2 and CHA2DS2-VASc scores could be useful in the determination of which patients should be closely followed up in order to prevent the development of PH after acute PE

68Ga-DOTATATE PET–CT imaging in carotid body paragangliomas

The aim of this study was to present our experience in the baseline evaluation of carotid body paragangliomas (CBP) with Ga-68-DOTATATE PET-CT