A Critical Systematic Review for Inhaled Corticosteroids on Lung Cancer Incidence: Not Yet Concluded Story

Background To systematically review studies on inhaled corticosteroids (ICS) and lung cancer incidence in chronic airway disease patients. Methods We conducted electronic bibliographic searches on OVID-MEDLINE, EM-BASE, and the Cochrane Database before May 2020 to identify relevant studies. Detailed data on the study population, exposure, and outcome domains were reviewed. Results Of 4,058 screened publications, 13 eligible studies in adults with chronic obstructive pulmonary disease (COPD) or asthma evaluated lung cancer incidence after ICS exposure. Pooled hazard ratio and odds ratio for developing lung cancer in ICS exposure were 0.81 (95% confidence interval, 0.64 to 1.02; I2=95.7%) from 10 studies and 1.02 (95% confidence interval 0.50 to 2.07; I2=94.7%) from three studies. Meta-regression failed to explain the substantial heterogeneity of pooled estimates. COPD and asthma were variously defined without spirometry in 11 studies. Regarding exposure assessment, three and 10 studies regarded ICS exposure as a time-dependent and fixed variable, respectively. Some studies assessed ICS use for the entire study period, whereas others assessed ICS use for 6 months to 2 years within or before study entry. Smoking was adjusted in four studies, and only four studies introduced 1 to 2 latency years in their main or subgroup analysis. Conclusion Studies published to date on ICS and lung cancer incidence had heterogeneous study populations, exposures, and outcome assessments, limiting the generation of a pooled conclusion. The beneficial effect of ICS on lung cancer incidence has not yet been established, and understanding the heterogeneities will help future researchers to establish robust evidence on ICS and lung cancer incidence

Tissue Adequacy and Safety of Percutaneous Transthoracic Needle Biopsy for Molecular Analysis in Non-Small Cell Lung Cancer: A Systematic Review and Meta-analysis

OBJECTIVE: We conducted a systematic review and meta-analysis of the tissue adequacy and complication rates of percutaneous transthoracic needle biopsy (PTNB) for molecular analysis in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We performed a literature search of the OVID-MEDLINE and Embase databases to identify original studies on the tissue adequacy and complication rates of PTNB for molecular analysis in patients with NSCLC published between January 2005 and January 2020. Inverse variance and random-effects models were used to evaluate and acquire meta-analytic estimates of the outcomes. To explore heterogeneity across the studies, univariable and multivariable meta-regression analyses were performed. RESULTS: A total of 21 studies with 2232 biopsies (initial biopsy, 8 studies; rebiopsy after therapy, 13 studies) were included. The pooled rates of tissue adequacy and complications were 89.3% (95% confidence interval [CI]: 85.6%-92.6%; I(2) = 0.81) and 17.3% (95% CI: 12.1%-23.1%; I(2) = 0.89), respectively. These rates were 93.5% and 22.2% for the initial biopsies and 86.2% and 16.8% for the rebiopsies, respectively. Severe complications, including pneumothorax requiring chest tube placement and massive hemoptysis, occurred in 0.7% of the cases (95% CI: 0%-2.2%; I(2) = 0.67). Multivariable meta-regression analysis showed that the tissue adequacy rate was not significantly lower in studies on rebiopsies (p = 0.058). The complication rate was significantly higher in studies that preferentially included older adults (p = 0.001). CONCLUSION: PTNB demonstrated an average tissue adequacy rate of 89.3% for molecular analysis in patients with NSCLC, with a complication rate of 17.3%. PTNB is a generally safe and effective diagnostic procedure for obtaining tissue samples for molecular analysis in NSCLC. Rebiopsy may be performed actively with an acceptable risk of complications if clinically required

White-Box AES Implementation Revisited

White-box cryptography is an obfuscation technique for protecting secret keys in software implementations even if an adversary has full access to the implementation of the encryption algorithm and full control over its execution platforms. This concept was presented by Chow et al. with white-box implementations of DES and AES in 2002. The strategy used in the implementations has become a design principle for subsequent white-box implementations. However, despite its practical importance, progress has not been substantial. In fact, it is repeated that as a proposal for a white-box implementation is reported, an attack of lower complexity is soon announced. This is mainly because most cryptanalytic methods target specific implementations, and there is no general attack tool for white-box cryptography. In this paper, we present an analytic toolbox on white-box implementations in this design framework and show how to reveal the secret information obfuscated in the implementation using this. For a substitution-linear transformation cipher on $n$ bits with S-boxes on $m$ bits, if $m_Q$-bit nonlinear encodings are used to obfuscate output values in the implementation, our attack tool can remove the nonlinear encodings with complexity $O(\frac{n}{m_Q}2^{3m_Q})$. We should increase $m_Q$ to obtain higher security, but it yields exponential storage blowing up and so there are limits to increase the security using the nonlinear encoding. If the inverse of the encoded round function $F$ on $n$ bits is given, the affine encoding $A$ can be recovered in $O(\frac{n}{m}\cdot{m_A}^32^{3m})$ time using our specialized affine equivalence algorithm, where $m_A$ is the smallest integer $p$ such that $A$ (or its similar matrix obtained by permuting rows and columns) is a block-diagonal matrix with $p\times p$ matrix blocks. According to our toolbox, a white-box implementation in the Chow et al.\u27s framework has complexity at most $O\left(\min\left\{ \tfrac{2^{2m}}{m}\cdot n^{m+4}, n\log n \cdot 2^{n/2}\right\}\right)$ within reasonable storage, which is much less than $2^n$. To overcome this, we introduce an idea that obfuscates two AES-128 ciphers at once with input/output encoding on 256 bits. To reduce storage, we use a sparse unsplit input encoding. As a result, our white-box AES implementation has up to 110-bit security against our toolbox, close to that of the original cipher. More generally, we may consider a white-box implementation on the concatenation of $t$ ciphertexts to increase security

CT Examinations for COVID-19: A Systematic Review of Protocols, Radiation Dose, and Numbers Needed to Diagnose and Predict

Purpose Although chest CT has been discussed as a first-line test for coronavirus disease 2019 (COVID-19), little research has explored the implications of CT exposure in the population. To review chest CT protocols and radiation doses in COVID-19 publications and explore the number needed to diagnose (NND) and the number needed to predict (NNP) if CT is used as a first-line test. Materials and Methods We searched nine highly cited radiology journals to identify studies discussing the CT-based diagnosis of COVID-19 pneumonia. Study-level information on the CT protocol and radiation dose was collected, and the doses were compared with each national diagnostic reference level (DRL). The NND and NNP, which depends on the test positive rate (TPR), were calculated, given a CT sensitivity of 94% (95% confidence interval [CI]: 91%–96%) and specificity of 37% (95% CI: 26%–50%), and applied to the early outbreak in Wuhan, New York, and Italy. Results From 86 studies, the CT protocol and radiation dose were reported in 81 (94.2%) and 17 studies (19.8%), respectively. Low-dose chest CT was used more than twice as often as standard-dose chest CT (39.5% vs.18.6%), while the remaining studies (44.2%) did not provide relevant information. The radiation doses were lower than the national DRLs in 15 of the 17 studies (88.2%) that reported doses. The NND was 3.2 scans (95% CI: 2.2–6.0). The NNPs at TPRs of 50%, 25%, 10%, and 5% were 2.2, 3.6, 8.0, 15.5 scans, respectively. In Wuhan, 35418 (TPR, 58%; 95% CI: 27710–56755) to 44840 (TPR, 38%; 95% CI: 35161–68164) individuals were estimated to have undergone CT examinations to diagnose 17365 patients. During the early surge in New York and Italy, daily NNDs changed up to 5.4 and 10.9 times, respectively, within 10 weeks. Conclusion Low-dose CT protocols were described in less than half of COVID-19 publications, and radiation doses were frequently lacking. The number of populations involved in a first-line diagnostic CT test could vary dynamically according to daily TPR; therefore, caution is required in future planning

CT analysis of thoracolumbar body composition for estimating whole-body composition

Background To evaluate the correlation between single- and multi-slice cross-sectional thoracolumbar and whole-body compositions. Methods We retrospectively included patients who underwent whole-body PET–CT scans from January 2016 to December 2019 at multiple institutions. A priori-developed, deep learning-based commercially available 3D U-Net segmentation provided whole-body 3D reference volumes and 2D areas of muscle, visceral fat, and subcutaneous fat at the upper, middle, and lower endplate of the individual T1–L5 vertebrae. In the derivation set, we analyzed the Pearson correlation coefficients of single-slice and multi-slice averaged 2D areas (waist and T12–L1) with the reference values. We then built prediction models using the top three correlated levels and tested the models in the validation set. Results The derivation and validation datasets included 203 (mean age 58.2years; 101 men) and 239 patients (mean age 57.8years; 80 men). The coefficients were distributed bimodally, with the first peak at T4 (coefficient, 0.78) and the second peak at L2-3 (coefficient 0.90). The top three correlations in the abdominal scan range were found for multi-slice waist averaging (0.92) and single-slice L3 and L2 (0.90, each), while those in the chest scan range were multi-slice T12–L1 averaging (0.89), single-slice L1 (0.89), and T12 (0.86). The model performance at the top three levels for estimating whole-body composition was similar in the derivation and validation datasets. Conclusions Single-slice L2–3 (abdominal CT range) and L1 (chest CT range) analysis best correlated with whole-body composition around 0.90 (coefficient). Multi-slice waist averaging provided a slightly higher correlation of 0.92.Key points In single-slice analysis, the L2–3 and L1 levels had the closest correlations with whole-body composition. Multi-slice waist averaging (0.92; correlation) showed a better correlation than the L2–3 single-slice analysis (0.90) in the abdomen. Multi-slice T12–L1 averaging (0.89) provided a comparable correlation to the L1 level in the chest (0.89).This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Trade Industry and Energy, the Ministry of Health & Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202011A03). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Impact of national policy on hand hygiene promotion activities in hospitals in Korea

Background After the Middle East respiratory syndrome coronavirus outbreak in Korea in 2015, the Government established a strategy for infection prevention to encourage infection control activities in hospitals. The new policy was announced in December 2015 and implemented in September 2016. The aim of this study is to evaluate how infection control activities improved within Korean hospitals after the change in government policy. Methods Three cross-sectional surveys using the WHO Hand Hygiene Self-Assessment Framework (HHSAF) were conducted in 2013, 2015, and 2017. Using a multivariable linear regression model, we analyzed the change in total HHSAF score according to survey year. Results A total of 32 hospitals participated in the survey in 2013, 52 in 2015, and 101 in 2017. The number of inpatient beds per infection control professionals decreased from 324 in 2013 to 303 in 2015 and 179 in 2017. Most hospitals were at intermediate or advanced levels of progress (90.6% in 2013, 86.6% in 2015, and 94.1% in 2017). In the multivariable linear regression model, total HHSAF score was significantly associated with hospital teaching status (β coefficient of major teaching hospital, 52.6; 95% confidence interval [CI], 8.9 to 96.4; P = 0.018), beds size (β coefficient of 100 beds increase, 5.1; 95% CI, 0.3 to 9.8; P = 0.038), and survey time (β coefficient of 2017 survey, 45.1; 95% CI, 19.3 to 70.9; P = 0.001). Conclusions After the new national policy was implemented, the number of infection control professionals increased, and hand hygiene promotion activities were strengthened across Korean hospitals.This work supported by grants (2017 N-E2805–00) from Korea Centers for Disease Control, which had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript

Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma

Background Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. Methods The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. Results The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10–3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. Conclusions Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.This work was supported by the National Research Foundation of Korea funded by the Korean Government (MSIT) (Grant No. NRF-2021R1A2C3005360) (YK) and the Ministry of Health & Welfare, Republic of Korea (Grant No. HI18C1876) (SSY). This study was supported by the Future Medicine 20 × 30 Project of the Samsung Medical Center (Grant No. SMX1230041, SMO1230021) and a Samsung Medical Center Research and Development Grant (Grant No. SMO1230661) (JKP)

Invertible Polynomial Representation for Private Set Operations

Abstract. In many private set operations, a set is represented by a polynomial over a ring Zσ for a composite integer σ, where Zσ is the message space of some additive homomorphic encryption. While it is useful for implementing set operations with polynomial additions and multiplications, a polynomial representation has a limitation due to the hardness of polynomial factorizations over Zσ. That is, it is hard to recover a corresponding set from a resulting polynomial over Zσ if σ is not a prime. In this paper, we propose a new representation of a set by a polynomial over Zσ, in which σ is a composite integer with known factorization but a corresponding set can be efficiently recovered from a polynomial except negligible probability. Note that Zσ[x] is not a unique factorization domain, so a polynomial may be written as a product of linear factors in several ways. To exclude irrelevant linear factors, we introduce a special encoding function which supports early abort strategy. As a result, our representation can be efficiently inverted by computing all the linear factors of a polynomial in Zσ[x] whose root locates in the image of encoding function. When we consider group decryption as in most private set operation protocols, inverting polynomial representations should be done without a single party possessing a factorization of σ. This is very hard for Paillier’s encryption whose message space is ZN with unknown factorization of N. Instead, we detour this problem by using Naccache-Stern encryption with message space Zσ where σ is a smooth integer with public factorization. As an application of our representation, we obtain a constant round privacy-preserving set union protocol. Our construction improves the complexity than the previous without honest majority assumption. It can be also used for constant round multi-set union protocol and private set intersection protocol even when decryptors do not possess a superset of the resulting set

Percutaneous transthoracic catheter drainage for lung abscess: a systematic review and meta-analysis

Objectives To evaluate the outcomes of patients receiving image-guided percutaneous catheter drainage (PCD) for lung abscesses in terms of treatment success, major complications, and mortality as well as the predictors of those outcomes. Methods Embase and OVID-MEDLINE databases were searched to identify studies on lung abscesses treated with PCD that had extractable outcomes. The outcomes were pooled using a random-intercept logistic regression model. Multivariate Firth's bias-reduced penalised-likelihood logistic regression analyses were performed to identify predictors of treatment success and complications. Methodological quality was assessed by summing scores of binary responses to items regarding selection, ascertainment of exposure and outcome, causality of follow-up duration, and reporting. Results From 26 studies with acceptable methodological quality (median score, 4; range, 3-5), 194 patients were included. The pooled rates of treatment success and major complications were 86.5% (95% confidence interval [CI], 78.5-91.8%; I-2 = 23%) and 8.1% (95% CI, 4.1-15.3%; I-2 = 26%), respectively. Four patients eventually died from uncontrolled lung abscesses (pooled rate, 1.5%; 95% CI, 0.2-11.1%; I-2 = 36%). Malignancy-related abscess (odds ratio [OR], 0.129; 95% CI, 0.024-0.724; p = .022) and the occurrence of a major complication (OR, 0.065; 95% CI, 0.02-0.193; p < .001) were significant predictors of treatment failure. Traversing normal lung parenchyma was the only significant risk factor for major complications (OR, 27.69; 95% CI, 7.196-123.603; p < .001). Conclusion PCD under imaging guidance was effective for lung abscess treatment, with a low complication rate. Traversal of normal lung parenchyma was the sole risk factor for complications, and malignancy-related abscesses and the occurrence of major complications were predictors of treatment failure.N