Predictive Value of Gross Extranodal Extension for Differentiated Thyroid Carcinoma Persistence/Recurrence

2021 ◽  
pp. 019459982110231
Author(s):  
Ying Kou ◽  
Guohua Shen ◽  
Zhuzhong Cheng ◽  
Anren Kuang
Keyword(s):  
High Risk ◽  
Thyroid Carcinoma ◽  
Risk Group ◽  
Differentiated Thyroid Carcinoma ◽  
Individual Risk ◽  
Intermediate Risk ◽  
Entire Cohort ◽  
Gene Group ◽  
Extranodal Extension ◽  
Disease Persistence

Objective We systematically investigated the predictive value of gross extranodal extension (gENE) for differentiated thyroid carcinoma persistence/recurrence. Study Design Retrospective study. Setting A tertiary care hospital. Methods This study was divided into 2 groups according to gENE status: the gENE group and non-gENE group. We compared the disease persistence/recurrence rates of these 2 groups in the entire cohort and by individual risk group (intermediate/high risk), analyzed whether gENE was an independent risk factor for disease persistence/recurrence, and explored the impact of gENE-specific features on disease persistence/recurrence. Results There were 989 patients who satisfied the inclusion criteria: 57 patients in the gENE group and 932 in the non-gENE group. The disease persistence/recurrence rate of the gENE group was higher than that of the non-gENE group in the entire cohort and by individual risk group ( P < .05 for each). Unexpectedly, the outcomes of the gENE group with intermediate risk were similar to those of the non-gENE group with high risk ( P = .72). For the entire cohort, gENE was an independent predictor for disease persistence/recurrence (odds ratio, 2.89; 95% CI, 1.39-6.00; P = .005). Specific features of gENE ( P > .05 for each) were not related to disease persistence/recurrence. Conclusion Patients with gENE and intermediate risk might be regraded as high risk. Specific features of gENE have no impact on disease persistence/recurrence.

scholarly journals Risk stratification of 282 differentiated thyroid cancers found incidentally in 1369 total thyroidectomies according to the 2015 ATA guidelines; implications for management and treatment

2018 ◽  
Vol 100 (5) ◽  
pp. 357-365 ◽  
Author(s):  
I Christakis ◽  
S Dimas ◽  
ID Kafetzis ◽  
N Roukounakis
Keyword(s):  
Thyroid Carcinoma ◽  
Preoperative Diagnosis ◽  
Radioactive Iodine ◽  
Risk Group ◽  
Differentiated Thyroid Carcinoma ◽  
Stage I ◽  
American Thyroid Association ◽  
Intermediate Risk ◽  
Incidental Group ◽  
Iodine Treatment

Introduction The purpose of this study was to evaluate the incidence of incidental differentiated thyroid carcinoma in thyroid operations for a benign preoperative diagnosis, to identify the risk factors involved and to risk stratify the cancer patients according to the 2015 American Thyroid Association (ATA) guidelines. Materials and methods The study was a retrospective review of all thyroidectomy operations performed in a single institution (January 2004 to January 2009). We excluded patients with a preoperative diagnosis of thyroid malignancy. Results Incidental differentiated thyroid carcinoma was diagnosed in 282/1369 patients (21%). The incidental group had a significantly higher number of males (19% vs 14%, P = 0.033) and a higher number of patients with histopathological evidence of thyroiditis (35% vs 25%, P = 0.004). There was a higher number of lymph nodes present in the incidental group but numbers did not reach statistical significance (17% vs 13%, P = 0.079). There were 270 cases in the ATA low-risk group (96%) and 12 cases in the ATA intermediate-risk group (4%). Patients with an ATA intermediate risk had a statistically higher number of capsule invasion, extrathyroidal extension and angioinvasion (P < 0.001, P < 0.001 and P < 0.001, respectively). Overall, 22% of patients with an incidental differentiated thyroid carcinoma should be considered for radioactive iodine 131I treatment. 29 of the 191 patients in American Joint Committee on Cancer stage I should be considered for radioactive iodine treatment (15%). Conclusions Males and patients with thyroiditis are at a higher risk for an incidental differentiated thyroid carcinoma. One of every five of patients diagnosed with cancer will need radioactive iodine treatment, even some patients with stage I disease.

scholarly journals Reappraising the Diagnostic Accuracy of Post-Treatment Whole-Body Scans for Differentiated Thyroid Carcinoma

2020 ◽  
Vol 52 (12) ◽  
pp. 834-840
Author(s):  
Carla Fernanda Nava ◽  
Rafael Selbach Scheffel ◽  
André Borsatto Zanella ◽  
Flavio Zelmanovitz ◽  
Ana Luiza Maia ◽  
...  
Keyword(s):  
High Risk ◽  
Thyroid Carcinoma ◽  
Diagnostic Accuracy ◽  
Distant Metastasis ◽  
False Negative ◽  
Differentiated Thyroid Carcinoma ◽  
Post Treatment ◽  
Whole Body ◽  
American Thyroid Association ◽  
Intermediate Risk

AbstractInitial treatment for differentiated thyroid carcinoma (DTC) often consists of surgery and the administration of radioiodine. In this context, post-treatment Whole-Body Scans (ptWBS) are currently recommended, but data on its diagnostic accuracy are rare. The aim of the study was to evaluate the performance of ptWBS for distant metastasis in DTC patients. We included DTC patients who received radioiodine and underwent ptWBS between 2009–2015. The medical data were independently reviewed by two specialists to evaluate the concordance of positive distant ptWBS uptake and distant metastasis documented by imaging exams (gold standard). We studied 268 DTC patients. The mean age was 46±16 years (82% women), and papillary thyroid carcinoma was diagnosed in 87% of the patients. The median tumor size was 2.7 cm, 40% had lymph node involvement, and 11% had distant metastasis. Twenty-eight patients (10%) had distant ptWBS uptake, and nine of them (32%) were false-positives. In addition, nine false-negative ptWBS uptakes were identified. The overall performance of ptWBS showed 68% sensitivity and 96% specificity with significantly different performance according to the American Thyroid Association (ATA) risk groups. While the ptWBS performance for ATA low-intermediate-risk showed 29% sensitivity, 97% specificity, and Kappa of 0.19, the ATA high-risk group ptWBS displayed high sensitivity (82%), specificity (100%), and good agreement (Kappa 0.74). ptWBS is useful for a subgroup of ATA high-risk DTC patients. The overall poor performance of ptWBS suggests that it should be reconsidered for routine use in ATA at low to intermediate risk: the exam has little value to this subgroup.

scholarly journals SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4540
Author(s):  
Johannes Korth ◽  
Benjamin Wilde ◽  
Sebastian Dolff ◽  
Jasmin Frisch ◽  
Michael Jahn ◽  
...  
Keyword(s):  
High Risk ◽  
Healthcare Workers ◽  
Risk Group ◽  
Close Contact ◽  
Virus Transmission ◽  
High Risk Group ◽  
Low Risk ◽  
University Hospital ◽  
Intermediate Risk ◽  
Igg Antibody

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

Association of pathological response to neoadjuvant pembrolizumab with tumor PD-L1 expression and high disease-free survival (DFS) in patients with resectable, local-regionally advanced, head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6006-6006
Author(s):  
Trisha Michel Wise-Draper ◽  
Vinita Takiar ◽  
Michelle Lynn Mierzwa ◽  
Keith Casper ◽  
Sarah Palackdharry ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Disease Free Survival ◽  
Immune Checkpoint Blockade ◽  
Skin Wound ◽  
High Risk Group ◽  
Pathological Response ◽  
Intermediate Risk ◽  
Positive Margins ◽  
Post Surgery

6006 Background: Patients with resected HNSCC, with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year DFS of 65% and 69%, respectively. Immune checkpoint blockade improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiotherapy (RT) synergizes with anti-PD-1. Therefore, we administered the PD-1 inhibitor pembrolizumab (pembro) pre- and post-surgery with adjuvant RT +/- cisplatin in patients with resectable, locoregionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093). Methods: Eligible patients received pembro (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembro (q3 wks x 6 doses) was administered with RT (60-66Gy) with or without weekly cisplatin (40mg/m2 X 6) for patients with high-risk and intermediate-risk features, respectively. The primary endpoint was 1-year DFS estimated by Kaplan Meier curves. Safety was evaluated by CTCAE v5.0. Pathological response (PR) to neoadjuvant pembro was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE), defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. PR was classified as no (NPR, < 20%), partial (PPR, ≥20% and < 90%) and major (MPR, ≥90%). Tumor PD-L1 immunohistochemistry was performed with 22c3 antibody and reported as combined positive score (CPS). Results: Ninety-two patients were enrolled. Seventy-six patients received adjuvant pembro and were evaluable for DFS. Patient characteristics included: median age 58 (range 27 – 80) years; 32% female; 88% oral cavity, 8% larynx, and 3% human papillomavirus negative oropharynx; 86% clinical T3/4 and 65% ≥2N; 49 (53%) high-risk (positive margins, 45%; ECE, 78%); 64% (44/69 available) had PD-L1 CPS ≥1. At a median follow-up of 20 months, 1-year DFS was 67% (95%CI 0.52-0.85) in the high-risk group and 93% (95%CI 0.84-1) in the intermediate-risk group. Among 80 patients evaluable for PR, TE scoring resulted in 48 NPR, 26 PPR and 6 MPR. Patients with PPR/MPR had significantly improved 1-year DFS when compared with those with NPR (100% versus 68%, p = 0.01; HR = 0.23). PD-L1 CPS ≥ 1 was not independently associated with 1-year DFS, but was highly associated with MPR/PPR (p = 0.0007). PPR/MPR in PD-L1 CPS < 1, ≥1 and ≥20, were estimated as 20, 55 and 90%, respectively. Grade ≥ 3 adverse events occurred in 62% patients with most common including dysphagia (15%), neutropenia (15%), skin/wound infections (10%), and mucositis (9%). Conclusions: PR to neoadjuvant pembro is associated with PD-L1 CPS≥1 and high DFS in patients with resectable, local-regionally advanced, HNSCC. Clinical trial information: NCT02641093.

scholarly journals A Mitochondrial Dysfunction and Oxidative Stress Pathway-Based Prognostic Signature for Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-32
Author(s):  
Yue Wu ◽  
Xi Zhang ◽  
Xian Wei ◽  
Huan Feng ◽  
Bintao Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Risk Group ◽  
Prognostic Significance ◽  
Individual Risk ◽  
Cell Renal Cell Carcinoma

Mitochondria not only are the main source of ATP synthesis but also regulate cellular redox balance and calcium homeostasis. Its dysfunction can lead to a variety of diseases and promote cancer and metastasis. In this study, we aimed to explore the molecular characteristics and prognostic significance of mitochondrial genes (MTGs) related to oxidative stress in clear cell renal cell carcinoma (ccRCC). A total of 75 differentially expressed MTGs were analyzed from The Cancer Genome Atlas (TCGA) database, including 46 upregulated and 29 downregulated MTGs. Further analysis screened 6 prognostic-related MTGs (ACAD11, ACADSB, BID, PYCR1, SLC25A27, and STAR) and was used to develop a signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses showed that the signature could accurately distinguish patients with poor prognosis and had good individual risk stratification and prognostic potential. Stratified analysis based on different clinical variables indicated that the signature could be used to evaluate tumor progression in ccRCC. Moreover, we found that there were significant differences in immune cell infiltration between the low- and high-risk groups based on the signature and that ccRCC patients in the low-risk group responded better to immunotherapy than those in the high-risk group (46.59% vs 35.34%, P = 0.008 ). We also found that the expression levels of these prognostic MTGs were significantly associated with drug sensitivity in multiple ccRCC cell lines. Our study for the first time elucidates the biological function and prognostic significance of mitochondrial molecules associated with oxidative stress and provides a new protocol for evaluating treatment strategies targeting mitochondria in ccRCC patients.

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Cardiovascular Events ◽  
Risk Group ◽  
Temporal Trends ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

scholarly journals The Impact of Preoperative Risk on the Association between Hypotension and Mortality after Cardiac Surgery: An Observational Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2057
Author(s):  
Vanja Ristovic ◽  
Sophie de Roock ◽  
Thierry G. Mesana ◽  
Sean van Diepen ◽  
Louise Y. Sun
Keyword(s):  
Cardiac Surgery ◽  
Risk Factor ◽  
High Risk ◽  
Hospital Mortality ◽  
Risk Group ◽  
High Risk Group ◽  
Group Care ◽  
Intermediate Risk ◽  
Intraoperative Hypotension ◽  
The Impact

Background: Despite steady improvements in cardiac surgery-related outcomes, our understanding of the physiologic mechanisms leading to perioperative mortality remains incomplete. Intraoperative hypotension is an important risk factor for mortality after noncardiac surgery but remains relatively unexplored in the context of cardiac surgery. We examined whether the association between intraoperative hypotension and in-hospital mortality varied by patient and procedure characteristics, as defined by the validated Cardiac Anesthesia Risk Evaluation (CARE) mortality risk score. Methods: We conducted a retrospective cohort study of consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass (CPB) from November 2009–March 2015. Those who underwent off-pump, thoracic aorta, transplant and ventricular assist device procedures were excluded. The primary outcome was in-hospital mortality. Hypotension was categorized by mean arterial pressure (MAP) of <55 and between 55–64 mmHg before, during and after CPB. The relationship between hypotension and death was modeled using multivariable logistic regression in the intermediate and high-risk groups. Results: Among 6627 included patients, 131 (2%) died in-hospital. In-hospital mortality in patients with CARE scores of 1, 2, 3, 4 and 5 was 0 (0%), 7 (0.3%), 35 (1.3%), 41 (4.6%) and 48 (13.6%), respectively. In the intermediate-risk group (CARE = 3–4), MAP < 65 mmHg post-CPB was associated with increased odds of death in a dose-dependent fashion (adjusted OR 1.30, 95% CI 1.13–1.49, per 10 min exposure to MAP < 55 mmHg, p = 0.002; adjusted OR 1.18 [1.07–1.30] per 10 min exposure to MAP 55–64 mmHg, p = 0.001). We did not observe an association between hypotension and mortality in the high-risk group (CARE = 5). Conclusions: Post-CPB hypotension is a potentially modifiable risk factor for mortality in intermediate-risk patients. Our findings provide impetus for clinical trials to determine if hemodynamic goal-directed therapies could improve survival in these patients.

scholarly journals Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592092821
Author(s):  
Li-Ting Liu ◽  
Yu-Jing Liang ◽  
Shan-Shan Guo ◽  
Hao-Yuan Mo ◽  
Ling Guo ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Risk Group ◽  
Risk Groups ◽  
Rank Test ◽  
Intermediate Risk ◽  
Free Survival ◽  
Alternative Treatment Strategy

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

Metformin Associated Lactic Acidosis in Clinical Practice – A Case Series

2020 ◽  
Author(s):  
Philipp Schädle ◽  
Otto Tschritter ◽  
Monika Kellerer
Keyword(s):  
Renal Replacement Therapy ◽  
High Risk ◽  
Lactic Acidosis ◽  
Replacement Therapy ◽  
Risk Score ◽  
Risk Group ◽  
Case Series ◽  
Individual Risk ◽  
Volume Depletion ◽  
Screening Criteria

Abstract Aims The aim of this case report is to specify the frequency and mortality of Metformin-Associated Lactic Acidosis (MALA) in emergency medicine, as the diagnosis seems to occur more often than estimated. Methods To identify the subjects, we developed screening criteria for MALA. We measured the serum metformin concentration to confirm the diagnosis in all patients fulfilling these criteria. Retrospectively the patients were grouped according to individual risk (according to a defined risk score) and the application of renal replacement therapy. Results From 2013 until 2018 we were able to identify 11 MALA patients revealing a frequency of 1:4,000 emergency patients. Six patients survived and five died in the follow-up. All three patients in the high-risk group died although all of them received renal replacement therapy. In the low-risk group (three patients, one with renal replacement therapy), all patients survived, while in the intermediate-risk group (five patients, one with renal replacement therapy) three patients survived and two died. Additional severe comorbidities also contributed to mortality. Conclusions Every patient matching the screening criteria of acute renal failure, lactic acidosis and continued intake of metformin can be considered a potential MALA case. A risk score assessment which includes severe comorbidities may help to identify high-risk individuals and should be evaluated in larger studies.To prevent MALA, patients should be trained to immediately interrupt their own metformin use when showing signs of volume depletion. Physicians should be aware of the additional risk factors such as co-medication with diuretics, ACE (angiotensin converting enzyme) ACE inhibitors and NSAIDs (non steroidal anti inflammatory drugs).

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