Deep-learning model to improve histological grading and predict upstaging of atypical ductal hyperplasia / ductal carcinoma in situ on breast biopsy.

AIMS: Risk stratification of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), diagnosed using breast biopsy, has great clinical significance. Clinical trials are currently exploring the possibility of active surveillance for low-risk lesions, whereas axillary lymph node staging may be considered during surgical planning for high-risk lesions. We aimed to develop a machine-learning algorithm based on whole-slide images of breast biopsy specimens and clinical information to predict the risk of upstaging to invasive breast cancer after wide excision. METHODS AND RESULTS: Patients diagnosed with ADH/DCIS on breast biopsy were included in this study, comprising 592 (740 slides) and 141 (198 slides) patients in the development and independent testing cohorts, respectively. Histological grading of the lesions was independently evaluated by two pathologists. Clinical information, including biopsy method, lesion size, and Breast Imaging Reporting and Data System (BI-RADS) classification of ultrasound and mammograms, were collected. Deep DCIS consisted of three deep neural networks to evaluate nuclear grade, necrosis, and stromal reactivity. Deep DCIS output comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. Deep DCIS highly correlated with the pathologists' evaluations of both slide- and patient-level labels. All five parameters of Deep DCIS were significantly associated with upstaging to invasive carcinoma in subsequent wide excisional specimens. Using multivariate logistic regression, Deep DCIS predicted upstaging to invasive carcinoma with an area under the curve (AUC) of 0.81, outperforming pathologists' evaluation (AUC, 0.71 and 0.69). After including clinical and hormone receptor status information, performance further improved (AUC, 0.87). This combined model retained its predictive power in two subgroup analyses: the first subgroup included unequivocal DCIS (excluding cases of ADH and DCIS suspicious for microinvasion) (AUC, 0.83), while the second excluded cases of high-grade DCIS (AUC, 0.81). The model was validated in an independent testing cohort (AUC, 0.81). CONCLUSION: This study demonstrated that deep-learning models can refine histological evaluation of ADH and DCIS on breast biopsies, which may help guide future treatment planning.

Creating Augmented Reality Holograms for Polytrauma Patients Using 3D Slicer and Holomedicine Medical Image Platform.

In traumatology physicians heavily rely on computed tomography (CT) 2D axial scans to identify and assess the patient's injuries after an accident. However, in some cases it can be difficult to rigorously evaluate the real extent of the damage considering only the bidimensional slices produced by the CT, and some life-threatening lesions can be missed. With the development of 3D holographic rendering and extended reality (XR) technology, CT images can be projected in a 3D format through head-mounted holographic displays, allowing multi-view from different angles and interactive slice intersections, thus increasing anatomical intelligibility. In this article, we explain how to import CT scans into holographic displays for 3D visualization and further compare the methodolgy with traditional bidimensional reading.

Effect of methylprednisolone treatment on COVID-19: An inverse probability of treatment weighting analysis.

OBJECTIVES: While corticosteroids have been hypothesized to exert protective benefits in patients infected with SARS-CoV-2, data remain mixed. This study sought to investigate the outcomes of methylprednisone administration in an Italian cohort of hospitalized patients with confirmed SARS-CoV-2 infection. METHODS: Patients with confirmatory testing for SARS-CoV-2 were retrospectively enrolled from a tertiary university hospital in Milan, Italy from March 1st to April 30th, 2020 and divided into two groups by administration of corticosteroids. Methylprednisolone was administered to patients not responding to pharmacological therapy and ventilatory support at 0.5-1mg/kg/day for 4 to 7 days. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between the steroid and non-steroid cohorts via inverse probability of treatment weight. Primary outcomes included acute respiratory failure (ARF), shock, and 30-day mortality among surviving patients. RESULTS: Among 311 patients enrolled, 71 patients received steroids and 240 did not receive steroids. The mean age was 63.1 years, 35.4% were female, and hypertension, diabetes, heart disease, and chronic pulmonary disease were present in 3.5%, 1.3%, 14.8% and 12.2% respectively. Crude analysis revealed no statistically significant reduction in the incidence of 30-day mortality (36,6% vs 21,7%; OR, 2.09; 95% CI, 1.18-3.70; p = 0.011), shock (2.8% vs 4.6%; OR, 0.60; 95% CI = 0.13-2.79; p = 0.514) or ARF (12.7% vs 15%; OR, 0.82; 95% CI = 0.38-1.80; p = 0.625) between the steroid and non-steroid groups. After IPTW analysis, the steroid-group had lower incidence of shock (0.9% vs 4.1%; OR, 0.21; 95% CI,0.06-0.77; p = 0.010), ARF (6.6% vs 16.0%; OR, 0.37; 95% CI, 0.22-0.64; p<0.001) and 30-day mortality (20.3% vs 22.8%; OR 0.86; 95% CI, 0.59-1.26 p = 0.436); even though, for the latter no statistical significance was reached. Steroid use was also associated with increased length of hospital stay both in crude and IPTW analyses. Subgroup analysis revealed that patients with cardiovascular comorbidities or chronic lung diseases were more likely to be steroid responsive. No significant survival benefit was seen after steroid treatment. CONCLUSIONS: Physicians should avoid routine methylprednisolone use in SARS-CoV-2 patients, since it does not reduce 30-day mortality. However, they must consider its use for severe patients with cardiovascular or respiratory comorbidities in order to reduce the incidence of either shock or acute respiratory failure.

Facial Motion Analysis beyond Emotional Expressions.

Facial motion analysis is a research field with many practical applications, and has been strongly developed in the last years. However, most effort has been focused on the recognition of basic facial expressions of emotion and neglects the analysis of facial motions related to non-verbal communication signals. This paper focuses on the classification of facial expressions that are of the utmost importance in sign languages (Grammatical Facial Expressions) but also present in expressive spoken language. We have collected a dataset of Spanish Sign Language sentences and extracted the intervals for three types of Grammatical Facial Expressions: negation, closed queries and open queries. A study of several deep learning models using different input features on the collected dataset (LSE_GFE) and an external dataset (BUHMAP) shows that GFEs can be learned reliably with Graph Convolutional Networks simply fed with face landmarks.

Association Between Aspirin Use and Sepsis Outcomes: A National Cohort Study.

BACKGROUND: Aspirin has anti-inflammatory and antiplatelet activities and directly inhibits bacterial growth. These effects of aspirin may improve survival in patients with sepsis. We retrospectively reviewed a large national health database to test the relationship between prehospital aspirin use and sepsis outcomes. METHODS: We conducted a retrospective population-based cohort study using the National Health Insurance Research Database of Taiwan from 2001 to 2011 to examine the relationship between aspirin use before hospital admission and sepsis outcomes. The association between aspirin use and 90-day mortality in sepsis patients was determined using logistic regression models and weighting patients by the inverse probability of treatment weighting (IPTW) with the propensity score. Kaplan-Meier survival curves for each IPTW cohort were plotted for 90-day mortality. For sensitivity analyses, restricted mean survival times (RMSTs) were calculated based on Kaplan-Meier curves with 3-way IPTW analysis comparing current use, past use, and nonuse. RESULTS: Of 52,982 patients with sepsis, 12,776 took aspirin before hospital admission (users), while 39,081 did not take any antiplatelet agents including aspirin before hospital admission (nonusers). After IPTW analysis, we found that when compared to nonusers, patients who were taking aspirin within 90 days before sepsis onset had a lower 90-day mortality rate (IPTW odds ratio [OR], 0.90; 95% confidence interval [CI], 0.88-0.93; P < .0001). Based on IPTW RMST analysis, nonusers had an average survival of 71.75 days, while current aspirin users had an average survival of 73.12 days. The difference in mean survival time was 1.37 days (95% CI, 0.50-2.24; P = .002). CONCLUSIONS: Aspirin therapy before hospital admission is associated with a reduced 90-day mortality in sepsis patients.

Risk Stratification in COVID-19 Pneumonia - Determining the Role of Lung Ultrasound.

LUS patterns of COVID-19 pneumonia have been described and shown to be characteristic. The aim of the study was to predict the prognosis of patients with COVID-19 pneumonia, using a score based on LUS findings. MATERIALS AND METHODS: An observational, retrospective study was conducted on patients admitted to Niguarda hospital with a diagnosis of COVID-19 pneumonia during the period of a month, from March 2nd to April 3rd 2020. Demographics, clinical, laboratory, and radiological findings were collected. LUS was performed in all patients. The chest was divided into 12 areas. The LUS report was drafted using a score from 0 to 3 with 0 corresponding to A pattern, 1 corresponding to well separated vertical artifacts (B lines), 2 corresponding to white lung and small consolidations, 3 corresponding to wide consolidations. The total score results from the sum of the scores for each area. The primary outcome was endotracheal intubation, no active further management, or death. The secondary outcome was discharge from the emergency room (ER). RESULTS: 255 patients were enrolled. 93.7 % had a positive LUS. ETI was performed in 43 patients, and 24 received a DNI order. The general mortality rate was 15.7 %. Male sex (OR 3.04, p = 0.014), cardiovascular disease and hypertension (OR 2.75, p = 0.006), P/F (OR 0.99, p < 0.001) and an LUS score > 20 (OR 2.52, p = 0.046) were independent risk factors associated with the primary outcome. Receiver operating characteristic (ROC) curve analysis for an LUS score > 20 was performed with an AUC of 0.837. Independent risk factors associated with the secondary outcome were age (OR 0.96, p = 0.073), BMI (OR 0.87, p = 0,13), P/F (OR 1.03, p < 0.001), and LUS score < 10 (OR 20.9, p = 0.006). ROC curve analysis was performed using an LUS score < 10 with an AUC 0.967. CONCLUSION: The extent of lung abnormalities evaluated by LUS score is a predictor of a worse outcome, ETI, or death. Moreover, the LUS score could be an additional tool for the safe discharge of patient from the ER.

Risk of out-of-hospital cardiac arrest among sepsis survivors in Taiwan: analysis of a nationwide population-based cohort.

OBJECTIVES: There is minimal literature examining the association of sepsis with out-of-hospital cardiac arrest (OHCA). Using a large national database, we aimed to quantify the risk of OHCA among sepsis patients after hospital discharge. DESIGN: Population-based cohort study. SETTING: Nationwide sepsis cohort retrieved from the National Health Insurance Research Database of Taiwan between 2000 and 2013. PARTICIPANTS: We included 17 304 patients with sepsis. After hospital discharge, 144 patients developed OHCA within 30 days and 640 between days 31 and 365. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcomes were OHCA events following hospital discharge for sepsis. To evaluate the independent association between sepsis and OHCA after a sepsis hospitalisation, we constructed two non-sepsis comparison cohorts using risk set sampling and propensity score matching techniques (non-infection cohort, non-sepsis infection cohort). We plotted the daily number and daily risk of OHCA within 1 year of hospital discharge between sepsis and matched non-sepsis cohorts. We used Cox regression to evaluate the risk of early and late OHCA, comparing sepsis to non-sepsis patients. RESULTS: Compared with non-infected patients, sepsis patients had a higher rate of early (HR 1.66, 95% CI: 1.27 to 2.16) and late (HR 1.19, 95% CI: 1.06 to 1.33) OHCA events. This association was independent of age, sex or cardiovascular history. Compared with non-sepsis patients with infections, sepsis patients had a higher rate of both early (HR 1.28, 95% CI: 1.00 to 1.63) and late (HR 1.13, 95% CI: 1.01 to 1.27) OHCA events, especially among patients with cardiovascular disease (OR 1.35, 95% CI: 1.01 to 1.81). CONCLUSIONS: Sepsis patients had increased risk of OHCA compared with matched non-sepsis controls, which lasted up to 1 year after hospital discharge.

Use of Calcium Channel Blockers and Risk of Active Tuberculosis Disease: A Population-Based Analysis.

Calcium channel blockers (CCBs) are known to reduce the availability of iron-an important mineral for intracellular pathogens. Nonetheless, whether the use of CCBs modifies the risk of active tuberculosis in the clinical setting remains unclear. To determine whether CCBs may modify the risk of active tuberculosis disease, we conducted a nested case-control study using the National Health Insurance Research Database of Taiwan between January 1999 and December 2011. Conditional logistic regression and disease risk score adjustment were used to calculate the risk of active tuberculosis disease associated with CCB use. Subgroup analyses investigated the effect of different types of CCBs and potential effect modification in different subpopulations. A total of 8164 new active tuberculosis cases and 816 400 controls were examined. Use of CCBs was associated with a 32% decrease in the risk of active tuberculosis (relative risk [RR], 0.68 [95% CI, 0.58-0.78]) after adjustment with disease risk score. Compared with nonuse of CCBs, the use of dihydropyridine CCBs was associated with a lower risk of tuberculosis (RR, 0.63 [95% CI, 0.53-0.79]) than nondihydropyridine CCBs (RR, 0.73 [95% CI, 0.57-0.94]). In contrast, use of ß-blockers (RR, 0.99 [95% CI, 0.83-1.12]) or loop diuretics (RR, 0.88 [95% CI, 0.62-1.26]) was not associated with lower risk of tuberculosis. In subgroup analyses, the risk of tuberculosis associated with the use of CCBs was similar among patients with heart failure or cerebrovascular diseases. Our study confirms that use of dihydropyridine CCBs decreases the risk of active tuberculosis.

Predictive Accuracy of Electrocardiographic Monitoring of Patients With Syncope in the Emergency Department: The SyMoNE Multicenter Study.

BACKGROUND: Arrhythmia is one of the most worrisome causes of syncope. Electrocardiographic (ECG) monitoring is crucial for the management of non-low-risk patients in the emergency department (ED). However, its diagnostic accuracy and optimal duration are unknown. We aimed to assess the diagnostic accuracy of ECG monitoring in non-low-risk patients with syncope in the ED. METHODS: This prospective multicenter observational study included adult patients presenting to the ED after syncope. Patients without an obvious etiology after ED evaluation who were classified by ED physicians as being at non-low risk of adverse events underwent ECG monitoring. We assessed sensitivity, specificity, and diagnostic yield (defined as the proportion of patients with true-positive ECG monitoring findings) of ECG monitoring in the identification of 7- and 30-day adverse and arrhythmic events according to monitoring duration. RESULTS: Of 242 patients included in the study, 29 patients had 7-day serious outcomes. Ten additional patients had serious outcomes at 30 days. The overall sensitivity, specificity, and diagnostic yield of ECG monitoring in the identification of 7-day adverse events were 0.55 (95% confidence interval [CI] = 0.36 to 0.74], 0.93 (95% CI = 0.89 to 0.96), and 0.07 (95% CI = 0.04 to 0.10), respectively. The sensitivity, specificity, and diagnostic yield of >12-hour ECG monitoring in the identification of 7-day adverse events were 0.89 (95% CI = 0.65 to 0.99), 0.78 (95% CI = 0.67 to 0.87), and 0.18 (95% CI = 0.12 to 0.28), respectively. Similar results were observed for 30-day adverse events. The median (interquartile range) ECG monitoring time was 6.5 (6 to 15) hours. ECG monitoring findings were positive in 31 patients. CONCLUSIONS: Although the overall diagnostic accuracy of ECG monitoring is fair, its sensitivity at >12 hours' duration is substantially higher. These results suggest that prolonged (>12 hours) monitoring is a safe alternative to hospital admission in the management of non-low-risk patients with syncope in the ED.

Fluoroquinolone use and serious arrhythmias: A nationwide case-crossover study.

AIM: Fluoroquinolones have been associated with life-threatening ventricular arrhythmias and even sudden cardiac death. We aimed to assess the temporal relationship of fluoroquinolone use and serious arrhythmias via a case-crossover analysis of a large cohort of serious arrhythmias patients. METHODS: In a national administrative database, we compare the distributions of fluoroquinolone exposure for the same patient across a 30-day period before the serious arrhythmia event and 5 randomly selected 30-day periods before the serious arrhythmia event. Odds ratios (ORs) and 95% Confidence Intervals (CIs) were estimated using conditional logistic regression analysis. RESULTS: From a total of 2 million participants, 7657 patients with serious arrhythmias were identified. Use of fluoroquinolones within the 30-day period before the event was significantly associated with increased risk for serious arrhythmia (OR:3.03, 95% CI:2.48, 3.71). The risk association was attenuated, but remained significant after adjustment for time-varying confounders (OR:1.48, 95% CI:1.18, 1.86). A consistent increase in risk of serious arrhythmia was observed for all time windows investigated (7 days, 14 days, 30 days, 60 days and 90 days). CONCLUSIONS: Exposure to fluoroquinolones was substantially associated with serious arrhythmic events, independent of the temporal proximity of fluoroquinolone prescription.

Oral Fluoroquinolone and the Risk of Aortic Dissection.

BACKGROUND: Previous studies raised safety concerns on the association between fluoroquinolone treatment and serious collagen disorders, aortic aneurysm and dissection (AA/AD). OBJECTIVES: This study sought to evaluate this association via a case-crossover analysis in a large national administrative database. METHODS: A case-crossover design was used to compare the distributions of fluoroquinolone exposure for the same patient across a 60-day period before the AA/AD event (hazard period) and 1 randomly selected 60-day period (referent period) between 60 to 180 days before the AA/AD events. In the sensitivity analysis, the authors repeated the main analysis using a 1:5 ratio of hazard period to referent period, to adjust for the effect of time-variant confounders. A disease-risk score-matched time control analysis was performed to investigate the potential time-trend bias. The risks were calculated by a conditional logistic regression model. RESULTS: A total of 1,213 hospitalized AA/AD patients were identified between 2001 and 2011. In the main case-crossover analysis, exposure to fluoroquinolone was more frequent during the hazard periods than during the referent periods (1.6% vs. 0.6%; odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for infections and co-medications, the risk remains significant (OR: 2.05; 95% CI: 1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure). Susceptible period analysis revealed that the use of fluoroquinolone within 60 days was associated with the highest risk of AA/AD. In the case-time-control analysis, there was no evidence that the observed association is due to temporal changes in fluoroquinolone exposure. CONCLUSIONS: Exposure to fluoroquinolone was substantially associated with AA/AD. This risk was modified by the duration of fluoroquinolone use and the length of the hazard period.

Trend and outcome of sepsis in children: A nationwide cohort study.

AIM: The aim of this study was to investigate the trend of incidence and outcome of paediatric sepsis in a population-based database. METHODS: Children with sepsis were identified from the 23 million nationwide health insurance claims database of Taiwan. Sepsis was defined by the presence of single ICD-9 code for severe sepsis or septic shock or a combination of ICD-9 codes for infection and organ dysfunction. We analysed the trend of incidence, mortality and source of infection in three age groups: infant (28 days to 1 year), child (1-9 years) and adolescent (10-18 years). RESULTS: From 2002 to 2012, we identified 38 582 paediatric patients with sepsis, of which 21.3% were infants, 52.8% were children and 25.8% were adolescents. The incidence of sepsis was 336.4 cases per 100 000 population in infants, 3.3 times higher than in children (101.5/100 000 cases) and 7.3 times higher than in adolescents (46.2/100 000 cases). While sepsis incidence decreased from 598.0 to 336.4 cases per 100 000 people in the infant population, it remained relatively unchanged in children and adolescents. For 90-day mortality, there were significant decreases in all three age groups (absolute decrease of 5.0% for infants, 3.7% for children and 14.4% for the adolescents). In the infant population, we observed a decrease in the incidence of lower respiratory tract infections, while the incidence of urinary tract infections remained unchanged. CONCLUSIONS: The incidence and mortality of sepsis among paediatric patients have decreased substantially between 2002 and 2012, especially among infants. The widespread use of Haemophilus influenzae and pneumococcal vaccines in infants could be a possible explanation.

A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome.

BACKGROUND: Whether statin treatment, proved by recent experimental studies to have an antimicrobial activity, exerts a drug- or a class-specific effect in sepsis remains unknown. METHODS: Short-term mortality in patients with sepsis was analyzed using data from the National Health Insurance Research Database. Use of statins was defined as the cumulative use of a specific statin (atorvastatin, simvastatin, or rosuvastatin) for > 30 days prior to the index sepsis admission. We determined the association between statin and sepsis outcome by multivariate-adjusted Cox models and propensity score (PS)-matched analysis, using a 1:1:1 PS matching technique. RESULTS: A total of 52,737 patients with sepsis fulfilled the inclusion criteria, of which 1,855 were prescribed atorvastatin, 916 were prescribed simvastatin, and 732 were prescribed rosuvastatin. Compared with nonusers, simvastatin (hazard ratio [HR], 0.72; 95% CI, 0.58-0.90) and atorvastatin (HR, 0.78; 95% CI, 0.68-0.90) were associated with an improved 30-day survival, whereas rosuvastatin was not (HR, 0.87; 95% CI, 0.73-1.04). Using rosuvastatin as the reference, atorvastatin (HR, 0.79; 95% CI, 0.64-0.99) and simvastatin (HR, 0.77; 95% CI, 0.59-0.99) had superior effectiveness in preventing mortality. CONCLUSIONS: Compatible with in vitro experimental findings, our results suggest that the drug-specific effect of statins on sepsis is not correlated to their lipid-lowering potency.

Risk of gastrointestinal perforation in patients taking oral fluoroquinolone therapy: An analysis of nationally representative cohort.

BACKGROUND: Fluoroquinolone is a commonly prescribed antimicrobial agent, and up to 20% of its users registers adverse gastroenterological symptoms. We aimed to evaluate the association between use of fluoroquinolone and gastrointestinal tract perforation. METHODS: We conducted a nested case-control study on a national health insurance claims database between 1998 and 2011. The use of fluoroquinolones was classified into current (< 60 days), past (61-365 days prior to the index date) and any prior year use of fluoroquinolones. We used the conditional logistic regression model to estimate rate ratios (RRs), adjusting or matching by a disease risk score (DRS). RESULTS: We identified a cohort of 17,510 individuals diagnosed with gastrointestinal perforation and matched them to 1,751,000 controls. Current use of fluoroquinolone was associated with the greatest increase in risk of gastrointestinal perforations after DRS score adjustment (RR, 1.90; 95% CI, 1.62-2.22). The risk of gastrointestinal perforation was attenuated for past (RR, 1.33; 95% CI, 1.20-1.47) and any prior year use (RR, 1.46; 95% CI, 1.34-1.59). To gain insights into whether the observed association can be explained by unmeasured confounder, we compared the risk of gastrointestinal perforation between fluoroquinolone and macrolide. Use of macrolide, an active comparator, was not associated with a significant increased risk of gastrointestinal perforation (RR, 1.11, 95%CI, 0.15-7.99). Sensitivity analysis focusing on perforation requiring in-hospital procedures also demonstrated an increased risk associated with current use. To mitigate selection bias, we have also excluded people who have never used fluoroquinolone before or people with infectious colitis, enteritis or gastroenteritis. In both of the analysis, a higher risk of gastrointestinal perforation was still associated with the use of fluoroquinolone. CONCLUSIONS: We found that use of fluoroquinolones was associated with a non-negligible increased risk of gastrointestinal perforation, and physicians should be aware of this possible association.

Alcohol drinking and risk of leukemia-a systematic review and meta-analysis of the dose-risk relation.

The association between alcohol and leukemia risk has been addressed in several studies in the past two decades, but results have been inconsistent. Therefore, we conducted a systematic review and meta-analysis to quantify the dose-risk relation. Through the literature search up to August 2013, we identified 18 studies, 10 case-control and 8 cohorts, carried out in a total of 7142 leukemia cases. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and we performed a dose-risk analysis using a class of nonlinear random-effects meta-regression models. Stratified analyses were carried out on leukemia subtypes and groups, in order to identify possible etiologic differences. Compared with nondrinkers, the relative risks (RRs) for all leukemia were 0.94 [95% confidence interval (CI), 0.85-1.03], 0.90 (95% CI, 0.80-1.01) and 0.91 (95% CI, 0.81-1.02) for any, light (≤ 1 drink/day) and moderate to heavy (>1 drink/day) alcohol drinking, respectively. The summary RRs for any alcohol drinking were 1.47 (95% CI, 0.47-4.62) for acute lymphoblastic leukemia, 0.94 (95% CI 0.77-1.15) for chronic lymphocytic leukemia, 1.02 (95% CI, 0.86-1.21) for acute myeloid leukemia and 0.93 (95% CI 0.75-1.14) for chronic myeloid leukemia. The subgroup analysis on geographical area for all leukemia combined showed RRs of 0.84 (95% CI, 0.76-0.93), 0.92 (95% CI, 0.83-1.01) and 1.32 (95% CI, 1.02-1.70) for studies conducted in America, Europe and Asia, respectively. We did not find an increased risk of leukemia among alcohol drinkers. If any, a modest favorable effect emerged for light alcohol drinking, with a model-based risk reduction of approximately 10% in regular drinkers.

Alcohol drinking and multiple myeloma risk--a systematic review and meta-analysis of the dose-risk relationship.

The role of alcohol intake in the risk for multiple myeloma (MM) is unclear, although some recent findings suggest an inverse relationship. To summarize the information on the topic, we carried out a systematic review and a dose-risk meta-analysis of published data. Through the literature search until August 2013, we identified 18 studies, eight case-control and 10 cohort studies, carried out in a total of 5694 MM patients. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and we carried out a dose-risk analysis using a class of nonlinear random-effects meta-regression models. The relative risk for alcohol drinkers versus non/occasional drinkers was 0.97 [95% confidence interval (CI), 0.85-1.10] overall, 0.96 (95% CI, 0.74-1.24) among case-control studies, and 1.00 (95% CI, 0.89-1.13) among cohort studies. Compared with nondrinkers, the pooled relative risks were 0.96 (95% CI, 0.81-1.13) for light (i.e. ≤ 1 drink/day) and 0.89 (95% CI, 0.74-1.07) for moderate-to-heavy (i.e. >1 drink/day) alcohol drinkers. The dose-risk analysis revealed a model-based MM risk reduction of about 15% at two to four drinks/day (i.e. 25-50 g of ethanol). The present meta-analysis of published data found no strong association between alcohol drinking and MM risk, although a modest favorable effect emerged for moderate-to-heavy alcohol drinkers.