Learning curve and period of experience required for the competent diagnosis of acute appendicitis using abdominal computed tomography: a prospective observational study

Objective To assess the learning curve of novice residents in diagnosing acute appendicitis using abdominal computed tomography (CT) scans. Methods This prospective observational study was conducted within a 4-month period from March 1 to June 30, 2015. After CT scans for right lower quadrant pain or similar acute abdomen were evaluated, postgraduate year 1 (PGY-1) residents completed an interpretation checklist. The primary outcome was evaluation of the learning curve for competent CT scan interpretation under suspicion of acute appendicitis. Secondary outcomes were cumulative numbers of accurate abdominal CT interpretations regardless of initial clinical impression and training period. Results PGY-1 residents recorded a total of 230 interpretation checklists. There were 53, 51, 46, 44, and 36 checklists recorded by individual residents and 92, 92, 91, 91, and 61 respective training days in the emergency department, excluding rotation periods in other departments. After 16 to 20 interpretations of abdominal CT scans performed under suspicion of acute appendicitis, the residents could diagnose acute appendicitis with more than 95% accuracy. Overall, the sensitivity and specificity for diagnosing acute appendicitis were 97% (95% confidence interval, 94 to 100) and 83% (95% confidence interval, 80 to 87), respectively. After 61 to 80 abdominal CT interpretations regardless of suspicion of acute appendicitis and after 41 to 50 days in training, PGY-1 emergency department residents could diagnose acute appendicitis with more than 95% accuracy. Conclusion PGY-1 residents require 16 to 20 checklist interpretations to acquire acceptable abdominal CT interpretation. After performing 61 to 80 CT scans regardless of suspicion of acute appendicitis, they could diagnose acute appendicitis with acceptable accuracy

Mutations at codons 178, 200-129, and 232 contributed to the inherited prion diseases in Korean patients

Background: Polymorphisms of the human prion protein gene (PRNP) contribute to the genetic determinants of Creutzfeldt-Jakob disease (CJD). Numerous polymorphisms in the promoter regions as well as the open reading frame of PRNP were investigated. Greater than 90% of Korean, Chinese, and Japanese carry the homozygote 129 MM codon. In Korea, polymorphisms have not been comprehensively studied, except codons 129 and 219 in PRNP among Korean CJD cases. Although polymorphisms at codons 129 and 219 play an important role in susceptibility to sporadic CJD, patients with other polymorphisms in PRNP exhibited critical distinctions of clinical symptoms. Methods: The genetic analyses of PRNP were carried out among probable CJD patients in comparison with the results from magnetic resonance imaging (MRI) and electroencephalogram (EEG). Results: The molecular analyses revealed that three mutations at codons D178N, E200K, and M232R in heterozygosity. Patients with the D178N and M232R mutations had a 129MM codon, whereas the patient with the E200K mutation showed 129MV heterozygosity. They all revealed strong 14-3-3 positive signals. The 67-year-old patient with the D178N-129M mutation showed progressive gait disturbance and dysarthria was in progress. The 58-year-old patient with the E200K mutation coupled to the 129MV codon had gait disturbance, dysarthria, agitation, and ataxic gait, and progressed rapidly to death 3 months from the first onset of symptoms. The 65-year-old patient with the M232R mutation showed rapidly progressive memory decline and gait disturbance, and died within 16 months after onset of symptoms. Conclusion: Despite differences in ethnicity, the clinical and pathological outcomes were similar to the respective mutations around the world, except absence of insomnia in D178N-129M subject.This research was funded by the Ministry for Health, Welfare and Family Affairs, Korea (grant number, 4800-4835-301-210).Shiga Y, 2007, J NEUROL, V254, P1509, DOI 10.1007/s00415-007-0540-9Kovacs GG, 2005, HUM GENET, V118, P166, DOI 10.1007/s00439-005-0020-1Zarranz JJ, 2005, J NEUROL NEUROSUR PS, V76, P1491, DOI 10.1136/jnnp.2005.056606KONG Q, 2004, PRION BIOL DIS, P673Spacey SD, 2004, ARCH NEUROL-CHICAGO, V61, P122Huang N, 2003, NEUROLOGY, V61, P354Kovacs GG, 2002, J NEUROL, V249, P1567, DOI 10.1007/s00415-002-0896-9Collinge J, 2001, ANNU REV NEUROSCI, V24, P519Schroter A, 2000, ARCH NEUROL-CHICAGO, V57, P1751Wong NKC, 2000, J MOL GRAPH MODEL, V18, P126Taniwaki Y, 2000, J NEUROL NEUROSUR PS, V68, P388Wiltfang J, 1999, J NEUROCHEM, V73, P2485Hainfellner JA, 1999, ANN NEUROL, V45, P812Swietnicki W, 1998, J BIOL CHEM, V273, P31048Riek R, 1998, P NATL ACAD SCI USA, V95, P11667, DOI 10.1073/pnas.95.20.11667Zerr I, 1998, ANN NEUROL, V43, P32ZEIDLER M, 1998, WHO MANUAL STRENGTHERosenmann H, 1997, NEUROLOGY, V49, P593Hoque MZ, 1996, ACTA NEUROPATHOL, V92, P441Nagayama M, 1996, NEUROLOGY, V47, P1313Steinhoff BJ, 1996, ARCH NEUROL-CHICAGO, V53, P162PARCHI P, 1995, CURR OPIN NEUROL, V8, P286BROWN P, 1994, ANN NEUROL, V35, P513PRUSINER SB, 1994, ANN NEUROL, V35, P385GABIZON R, 1994, PHILOS T ROY SOC B, V343, P385HITOSHI S, 1993, J NEUROL SCI, V120, P208GOLDFARB LG, 1992, SCIENCE, V258, P806BROWN P, 1991, EUR J EPIDEMIOL, V7, P469STAHL N, 1990, BIOCHEMISTRY-US, V29, P8879BROWN P, 1986, ANN NEUROL, V20, P597

Quality of life in patients with diabetic nephropathy: findings from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort

Background Diabetic nephropathy (DN) can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences between DN patients and patients with other chronic kidney diseases (CKDs). Methods The analysis included subjects (n = 1,766) from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form questionnaire. After implementing propensity score matching (PSM) using factors that affect the QoL of DN patients, QoL differences between DN and non-DN participants were examined. Results Among all DN patients (n = 390), higher QoL scores were found for taller subjects, and lower scores were found for those who were unemployed or unmarried, received Medical Aid, had lower economic status, had higher platelet counts or alkaline phosphatase levels, or used clopidogrel or insulin. After PSM, the 239 matched DN subjects reported significantly lower patient satisfaction (59.9 vs. 64.5, p = 0.02) and general health (35.3 vs. 39.1, p = 0.04) than the 239 non-DN subjects. Scores decreased in both groups during the 5-year follow-up, and the scores in the work status, sexual function, and role-physical domains were lower among DN patients than non-DN patients, though those differences were not statistically significant. Conclusion Socioeconomic factors of DN were strong risk factors for impaired QoL, as were high platelet, alkaline phosphatase, and clopidogrel and insulin use. Clinicians should keep in mind that the QoL of DN patients might decrease in some domains compared with non-DN CKDs

Lactational coumestrol exposure increases ovarian apoptosis in adult rats

This study is the first to examine the increased apoptosis in the adult rat ovary after lactational exposure to coumestrol (COU), a potent phytoestrogen. Lactating dams were gavaged at doses of 0.01, 0.1, 1, and 10 mg/kg COU during the lactation period and the reproductive effects of female pups were investigated in young adults. Rats were sacrificed at postnatal days (PND) 81–84. Ovarian weights were reduced significantly at 0.1 and 1.0 mg/kg COU. The reduction in the ovarian weight occurred in parallel with an increase in the apoptosis at PND 135–140. A marked dose-dependent increase in the expressions of active caspase-3 and -7 was observed in ovarian granulosa cells. Immunostaining for active caspase-3 and the TUNEL staining of apoptotic cells were also increased in ovaries exposed to COU in a dose-dependent manner. These results suggest new sights into the effect of lactational exposure to COU on the female reproductive health

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Characterization of <span style="font-variant: small-caps">l</span>-Arabinose Isomerase from <i>Klebsiella pneumoniae</i> and Its Application in the Production of <span style="font-variant: small-caps">d</span>-Tagatose from <span style="font-variant: small-caps">d</span>-Galactose

d-Tagatose, a functional sweetener, is converted from d-galactose by l-arabinose isomerase, which catalyzes the conversion of l-arabinose to l-ribulose. In this study, the araA gene encoding l-arabinose isomerase from Klebsiella pneumoniae was cloned and expressed in Escherichia coli, and the expressed enzyme was purified and characterized. The purified l-arabinose isomerase, a soluble protein with 11.6-fold purification and a 22% final yield, displayed a specific activity of 1.8 U/mg for d-galactose and existed as a homohexamer of 336 kDa. The enzyme exhibited maximum activity at pH 8.0 and 40 °C in the presence of Mn2+ and relative activity for pentoses and hexoses in the order l-arabinose > d-galactose > l-ribulose > d-xylulose > d-xylose > d-tagatose > d-glucose. The thermal stability of recombinant E. coli cells expressing l-arabinose isomerase from K. pneumoniae was higher than that of the enzyme. Thus, the reaction conditions of the recombinant cells were optimized to pH 8.0, 50 °C, and 4 g/L cell concentration using 100 g/L d-galactose with 1 mM Mn2+. Under these conditions, 33.5 g/L d-tagatose was produced from d-galactose with 33.5% molar yield and 67 g/L/h productivity. Our findings will help produce d-tagatose using whole-cell reactions, extending its industrial application