Retrograde inspection vs standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial

BACKGROUND The adenoma detection rate(ADR) is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening colonoscopy. However, adenoma miss rates reach up to 26% and studies have shown that a second inspection of the right colon in retroflected view(RFV) can increase ADR.AIM To assess whether inspection of the whole colon in RFV compared to standard forward view(SFV) can increase ADR.METHODS Patients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two arms. In RFV arm colonoscopy was initially performed with SFV, followed by a second inspection of the whole colon in RFV. In the SFV arm first withdrawal was performed with SFV, followed by a second inspection of the whole colon again with SFV. Number, size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate containers.RESULTS Two hundred and five patients were randomly assigned to the RFV(n = 101) and SFV(n = 104) arm. In the RFV arm, both polyp detection rate(PDR) and ADR were increased under second inspection in RFV(PDR 1~(st) SFV: 39.8%, PDR 2~(nd)RFV: 46.6%; ADR 1~(st) SFV: 35.2%, ADR 2~(nd) RFV: 42%). Likewise, in the SFV arm,PDR and ADR were increased under second inspection(PDR 1~(st) SFV: 37.5%, PDR 2~(nd) SFV: 46.6%; ADR 1~(st) SFV: 34.1%, ADR 2~(nd)SFV: 44.3%) with no significant differences in ADR and PDR between the SFV and RFV arm. Mean number of adenomas per patient(APP) was increased in the RFV and SFV(APP RFV arm: 1~(st) SFV: 1.71; 2~(nd) RFV: 2.38; APP SFV arm: 1~(st) SFV: 1.83, 2~(nd)SFV:2.2). The majority of adenomas additionally found during second inspection in RFV or in SFV were located in the transverse and left-sided colon and were 5 mm in size.CONCLUSION Second inspection of the whole colon leads to increased adenoma detection with no differences between SFV and RFV. Hence, increased detection is most likely a feature of the second inspection itself but not of the inspection mode.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a Neonate—Rapid Tumor Regression Documented by Real Time 3D Echocardiography

The presented case reports on successful treatment with everolimus in a neonate with left ventricular giant rhabdomyoma. The authors used a different dosage regime compared to literature and documented rapid tumor regression by 3D echocardiography.     

Mycophenolate Mofetil Use Is Associated with Decreased Risk of Late Acute Rejection in Adult Liver Transplant Recipients

Mycophenolate mofetil (MMF) used in a triple-drug regimen has been shown to decrease acute rejection rates, compared to a double-drug regimen. The impact of MMF on late acute rejection (LAR) episodes has not been well described. To investigate the risk of LAR (rejection > or = 6 months post-transplantation) data from the Scientific Registry of Transplant Recipients (SRTR) were used. We studied adult primary liver transplant recipients transplanted between June 1, 1995, and April 30, 2004, with hepatitis C virus (HCV) (n = 3356), hepatitis B virus (HBV) (n = 550) or a nonviral (n = 5740) primary cause of liver disease who were recorded as receiving continuous 3-(MMF + Tacro + steroids) versus 2-drug (Tacro + steroids) therapy for at least 6 months immediately post transplantation. Kaplan-Meier analysis showed significantly lower LAR rates 4 years post-transplant in 3- versus 2-drug HCV, HBV and nonviral disease patients. Multivariate regression confirmed 3- versus 2-drug therapy to be associated with a decreased risk of LAR. Late graft survival was significantly lower at 4 years post-transplant for patients with LAR 6-12 months post-transplantation versus patients with early rejection (78.0% vs. 87.0%, p < 0.001) and no rejection (88.1%, p < 0.001). Three-drug versus 2-drug therapy for a minimum of 6 months may offer a better treatment strategy to avoid the consequences and expense of LAR episodes.     

Entrapment of pacemaker lead by a large netlike Eustachian valve within the right atrium

Summary During pacemaker implantation in a patient with permanent atrial fibrillation, it remained impossible to advance a passive fixation lead with fins through the right atrium. However, a lead with a retractable screw easily passed the right atrium and was positioned in the right ventricle. Transesophageal echocardiography revealed an extensive net–like perforated Eustachian valve within the right atrium that had caused entrapment of the anchor fins during lead implantation. Remnants of embryonal structures within the right atrium should be considered a rare possible barrier during pacemaker implantation.     

Pelvic Ring Fractures: Utility of Clinical Examination in Patients with Impaired Consciousness or Tracheal Intubation

Abstract Objective: To define the diagnostic accuracy of clinical examination in patients with impaired consciousness or endotracheal intubation to detect pelvic ring fractures and to identify those with severe bleeding. Methods: Included in this prospective data collection with retrolective data analysis were a consecutive series of blunt trauma victims with either a Glasgow Coma Scale ≤ 13 or tracheal intubation. Clinical examination comprised testing for stability of the iliac wings. Results: From 784 subjects (injury severity score 23.3 ± 17.4) 93 patients (11.9%) were found to have a pelvic ring fracture. Clinical instability of the pelvic ring was found in 42 patients. There was only one false positive. Fifty-two fractures could not be identified by clinical examination, including nine fractures (17%) that required surgical fracture stabilization (sensitivity of clinical examination 44.1%). Seventeen fractures (18.3%) were associated with a blood loss larger than 20% of circulating blood volume. Sixteen of those were identified by clinical instability of the pelvic ring (sensitivity 94.1%, specificity 97.0%, positive predictive value 38.1%, negative predictive value 99.9%). Conclusions: Clinical examination for stability of the pelvis in this selected group of patients missed a significant number of pelvic ring fractures including fractures that require surgical stabilization. The finding of a clinically unstable identifies most of the patients with the pelvic ring fracture being a major source of bleeding. A stable pelvis makes pelvic ring fracture as being the source of bleeding quite unlikely.     

Quantification of Basal and Stimulated ROS Levels as Predictors of Islet Potency and Function

We have developed a luminol-based assay using intact islets, which allows for quantification of reactive oxygen species (ROS). In addition, an index capable of characterizing metabolic and mitochondrial integrity prior to transplantation was created based on the capacity of islets to respond to high glucose and rotenone (mitochondrial respiratory chain complex I inhibitor) by production of ROS. To validate this assay, lipid peroxidation and antioxidative defense capacity were evaluated by detection of malondialdehyde (MDA) levels and glutathione peroxidase activity (GPx), respectively. Also, flow cytometric analyses of ROS (dihydroethidine), apoptosis (Annexin V, active caspases), necrosis (Topro3), and mitochondrial membrane potential (JC-1) were done in parallel to correlate with changes in luminol-measured ROS. ATP/ADP ratios were quantified by HPLC and the predictive value of ROS measurement on islet functional potency was correlated with capacity to reverse diabetes in a streptozotocin-induced diabetic NOD.scid mouse model as well as in human transplant recipients. Our data demonstrate that levels of ROS in islets correlate with the percentage of apoptotic cells and their functional potency in vivo. The ROS indices following glucose and rotenone exposure are indicative of metabolic potency and mitochondrial integrity and can be used as surrogate markers to evaluate the quality of islets prior to transplantation.     

Body Mass Index and Glomerular Hyperfiltration in Renal Transplant Recipients: Cross-Sectional Analysis and Long-Term Impact

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.     

Karzinomassoziierte Retinopathie (CAR) bei Mammakarzinom und Karzinoid

Fragestellung: Die Karzinomassoziierte Retinopathie (CAR) stellt ein seltenes paraneoplastisches Syndrom dar, das bislang am h?ufigsten bei kleinzelligen Bronchialkarzinomen beschrieben wurde. Wir berichten über 3 Patientinnen mit CAR in Gegenwart eines Mammakarzinoms bzw. eines Karzinoids der Cervix uteri. Patienten und Methode: Es wurden biomikroskopische, perimetrische, angiographische und elektrophysiologische Befunde erhoben. Au?erdem erfolgte eine Testung der Immunreaktivit?t der Seren an humaner Retina. Ergebnisse: Die Befunde umfa?ten ringf?rmige Gesichtsfelddefekte mit statokinetischer Dissoziation und eine pathologische St?bchen- und Zapfenantwort im ERG. Bei 1 Patientin wurde immunhistochemisch eine Reaktion im Bereich der Photorezeptorinnensegmente, der ?u?eren K?rnerschicht sowie der ?u?eren plexiformen Schicht bei fehlendem Nachweis von Antik?rpern gegen Recoverin gefunden. Diskussion: Neben dem kleinzelligen Bronchialkarzinom k?nnen auch andere Prim?rtumoren mit einer CAR vergesellschaftet sein. Der Nachweis von retinalen Autoantik?rpern unterstützt die Annahme einer tumorinduzierten Immunantwort aufgrund der Expression identischer Epitope durch die Tumorzellen. Dabei kommen offensichtlich verschiedene retinale Proteine als Autoantigene in Betracht.