Exploratory analysis of serum Krebs von den Lungen-6, blood gas analysis & Brixia score in determining COVID-19 severity & mortality.

Background & objectives Krebs von den Lungen-6 (KL-6) is primarily expressed by the damaged type II pneumocytes. In this context, the relationship of KL-6 with blood gas analysis (BGA) parameters and Brixia score is still limitedly discussed. This study aims to analyze the correlation of KL-6, BGA and Brixia scores to the severity and mortality of COVID-19. Methods A cross-sectional study was conducted in adult COVID-19 positive individuals at Universitas Airlangga Hospital, Surabaya, East Java, Indonesia, from March to August 2021. KL-6, BGA, and Brixia scores were compared according to severity (severe vs. non-severe) and mortality (non-survivor vs. survivor). The receiver operating characteristic (ROC) analysis was also performed to define the optimal cut-off, sensitivity, as well as the specificity of KL-6, BGA and Brixia scores to determine the COVID-19 severity and mortality. Results Total 35 severe and 20 non-severe COVID-19 positive individuals were enrolled in this study. Of those, there were 22 non-survivors. No significant difference in serum KL-6 levels was observed in the severity and mortality groups. KL-6 and HCO3- had positive correlation in the severe group (r=0.37). KL-6 and Brixia scores showed a significant negative correlation among COVID-19 positive individuals (r=-0.283; P=0.036). KL-6 and Brixia scores together served as the best severity markers in the current study [AUC 0.809 (0.697-0.920); Sn/Sp=0.686/0.900)], followed by KL-6 and P/F ratio [AUC 0.800 (0.637-0.963); Sn/Sp=0.971/0.750]. Interpretation & conclusions The findings of this study suggest that KL-6 has the potential to be a useful adjunct laboratory parameter to the BGA and Brixia score representing COVID-19 severity and mortality.

Unusual Presentations of Thyrotoxic Tricuspid and Mitral Regurgitations in 62 Adults: A Systematic Review of Case Reports with In-depth Pathophysiological Review.

Background: Thyrotoxicosis is related to cardiovascular mortality. This can be caused by several clinical manifestations involving the rare provocation of tricuspid regurgitation (TR) and mitral regurgitation (MR). However, there are still no clear data on thyrotoxic TR and/or MR. This study examines the progression of TR, MR, heart failure (HF) and pulmonary hypertension (PH) in response to the thyrotoxic heart manifestations, clinical characteristics and treatment approaches. Methods: A PRISMA-based systematic search was conducted using PubMed and other databases up to 17 June 2023. The outcomes of this study were TR, MR, HF and PH with their progression on follow-up, clinical characteristics and treatment approaches. Results: A total of 57 case reports involving 62 patients (45.77 ± 13.41 years) were included in this study. They were predominantly women (n=50; 80.65%) and diagnosed with Graves' disease (n=41; 75.81%). All patients were diagnosed with thyrotoxicosis, and this included 23 (37.10%) cases of thyroid storm. From echocardiographic studies, several patients improved clinically within the first 6 months of follow-up, including 20 TR patients (83.33%) in 6 months, nine MR patients (69.23%) in 3 months, eight HF patients (66.67%) in 2 months and 16 PH patients (76.19%) in 6 months. Conclusion: Several mechanisms are involved in thyrotoxic TR and/or MR, including the direct thyroid hormone effect and the indirect effect of other hyperthyroidism-associated factors. Patients with thyrotoxic TR and/or MR, including those with HF and PH, can experience clinical and structural improvements following hyperthyroidism treatment in the first 6 months.

An in-depth investigation of serum Krebs von den Lungen-6 and other biomarkers in COVID-19 severity and mortality.

Krebs von den Lungen-6 (KL-6) is a glycoprotein mainly expressed by type II pneumocytes and recently known as a lung injury biomarker. However, the number of studies is still limited, especially in Indonesian COVID-19 populations. Therefore, we aim to provide correlation, sensitivity, and specificity analyses of KL-6 and other biomarkers in Indonesian COVID-19 severity and mortality. We conducted a cross-sectional study involving adult COVID-19 patients at Universitas Airlangga Hospital, Surabaya, East Java, Indonesia, between March 26, 2021, and August 25, 2021. KL-6 and other biomarker levels were compared according to severity (severe versus non-severe) and mortality (non-survivor versus survivor). We also included the receiver operating characteristic analysis to define the optimal cut-off, sensitivity, and specificity of KL-6 to determine COVID-19 severity and mortality. We enrolled 78 COVID- 19 patients (23 non-survivors), including 39 non-severe and 39 severe patients. There was no significant difference in serum KL-6 levels, neither in severity nor mortality groups. KL-6 had the strongest positive correlations with ferritin in severe patients (r=0.313) and non-survivors (r=0.467). We observed that the best sensitivity was KL-6 combined with platelet-to- lymphocyte ratio (PLR) (0.818) in severe patients and with neutrophil-to-lymphocyte ratio (NLR)/PLR/ferritin/C-reactive protein (0.867) in non-survivors. In contrast, the best specificity was found when KL-6 was combined with NLR/D-dimer (0.750) in severe patients and with D-dimer (0.889) in non-survivors. Serum KL-6 is a useful auxiliary laboratory evaluation index for COVID-19 lung injury to depict its severity and mortality.

Risk factors and 26-years worldwide prevalence of endoscopic erosive esophagitis from 1997 to 2022: a meta-analysis.

Erosive esophagitis (EE) is the part of gastroesophageal reflux disease (GERD) spectrum and may progress to esophageal adenocarcinoma. Due to its progressivity and unclear prevalence, we aim to identify the factors contributing in EE to decide the need for further examination. We performed a PRISMA 2020-based systematic search through PubMed and other resources up to June 2, 2022. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). The odds ratio (OR) of each factor and worldwide prevalence of EE were measured. There are 114 observational studies included with a total of 759,100 participants. Out of 29 factors, the significant risk factors are age ≥ 60 y.o. (OR 2.03 [1.81-2.28]), White/Caucasian (OR 1.67 [1.40-1.99]), unmarried (OR 1.08 [1.03-1.14]), having GERD ≥ 5 years (OR 1.27 [1.14-1.42]), general obesity (OR 1.78 [1.61-1.98]), central obesity (OR 1.29 [1.18-1.42]), diabetes mellitus (DM) (OR 1.24 [1.17-1.32]), hypertension (OR 1.16 [1.09-1.23]), dyslipidemia (OR 1.15 [1.06-1.24]), hypertriglyceridemia (OR 1.42 [1.29-1.57]), hiatal hernia (HH) (OR 4.07 [3.21-5.17]), and non-alcoholic fatty liver disease (NAFLD) (OR 1.26 [1.18-1.34]). However, H. pylori infection (OR 0.56 [0.48-0.66]) and atrophic gastritis (OR 0.51 [0.31-0.86]) are protective towards EE. This study demonstrates that age, ethnicity, unmarried, long-term GERD, metabolic diseases, HH, and NAFLD act as risk factors for EE, whereas H. pylori infection and atrophic gastritis act as protective factors. These findings may enable a better understanding of EE and increase greater awareness to address its growing burden.

Baseline serum Mac-2 binding protein glycosylation isomer as a predictor of hepatocellular carcinoma in chronic hepatitis B patients: a systematic review and meta-analysis.

Background: A minimally invasive tool to promptly predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is currently needed. In this study, we aimed via a meta-analysis to identify the serum Mac-2 binding protein glycosylation isomer (M2BPGi) as a novel glycoprotein-based liver fibrosis marker for predicting HCC in CHB patients. Methods: We conducted a systematic search on PubMed, Scopus, ProQuest, Wiley Online Library, and CINAHL Plus (via EBSCOhost). The articles were screened based on several eligibility criteria and were further assessed for study qualities using the Newcastle-Ottawa Scale. The outcomes were presented as standard mean difference (SMD), hazard ratio (HR), and predictive accuracy parameters of a baseline cutoff index (COI) for serum M2BPGi. Results: Fourteen studies involving 5918 CHB patients were included in this systematic review and meta-analysis. Baseline COI serum M2BPGi was significantly higher in CHB patients who developed HCC than in those who did not (SMD 1.32, 95% confidence interval [CI] 0.91-1.72). A significant HCC risk prediction was also observed (multivariate HR 1.18, 95%CI 1.05-1.32). Baseline COI serum M2BPGi could predict HCC with a pooled sensitivity of 74% (95%CI 50-89%), specificity of 80% (95%CI 65-90%), and area under the summary receiver operating characteristic curve of 0.84 (95%CI 0.81-0.87). Conclusion: High baseline COI serum M2BPGi may predict the development of HCC in CHB patients with moderate-to-high accuracy.

Risk factors for exocrine pancreatic insufficiency after pancreatic surgery: a systematic review and meta-analysis.

BACKGROUND: Patients should be informed beforehand of the risk factors for exocrine pancreatic insufficiency (ExoPI) after pancreatic surgery; however, there are no clear identified risk factors for this condition. This study aimed to identify the preoperative, perioperative and postoperative risk factors for ExoPI after pancreatic surgery. METHODS: We conducted a systematic search of PubMed, Scopus, SAGE, CINAHL Plus and Taylor & Francis from inception to Mar. 7, 2021, for full-text articles that included patients who had undergone pancreatic surgery. The primary outcome was the number of ExoPI events and any risk factors evaluated. We used the Newcastle-Ottawa Scale to assess study quality. RESULTS: Twenty studies involving 4131 patients (2312 [52.3%] male, mean age 60.12 [standard deviation 14.07] yr) were included. Of the 4131 patients, 1651 (40.0%) had postoperative ExoPI. Among the 11 factors evaluated, the significant risk factors were preoperative main pancreatic duct (MPD) diameter greater than 3 mm (odds ratio [OR] 4.50, 95% confidence interval [CI] 1.06-19.05), pancreaticoduodenectomy (PD) as the surgical treatment procedure (OR 3.31, 95% CI 1.92-5.68), pancreaticogastrostomy (PG) as the anastomotic procedure (OR 3.13, 95% CI 1.83-5.35), hard pancreatic texture (OR 2.93, 95% CI 1.99-4.32) and adjuvant chemotherapy (OR 2.50, 95% CI 1.54-4.04). Gender, history of diabetes mellitus or endocrine pancreatic insufficiency (EndoPI), underlying diseases, de novo diabetes or EndoPI, pylorus-preserving PD and postoperative pancreatic fistula were not risk factors for ExoPI after pancreatic surgery. CONCLUSION: Preoperative MPD diameter greater than 3 mm, PD, PG reconstruction, hard pancreatic texture and adjuvant chemotherapy were risk factors for the development of ExoPI after pancreatic surgery. The findings should provide useful information for patients to reduce postoperative dissatisfaction and improve quality of life.

Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19 Lung Injury: A Systematic Review and Meta-Analysis.

Background: Lung injury is common in coronavirus disease 2019 (COVID-19) patients. The severity of lung injury appears to be reflected in serum Krebs von den Lungen-6 (KL-6), a glycoprotein expressed on type II alveolar epithelium. This study aims to assess the role of serum KL-6 in reflecting the severity of lung injury in COVID-19 patients. Methods: A systematic search was conducted in Scopus, PubMed, Wiley Online Library, and ProQuest. Articles were screened based on several eligibility criteria and assessed for study quality using Newcastle-Ottawa Scale. Results: This systematic review included four studies involving a total of 151 adult COVID-19 patients. Pooled analysis revealed that serum KL-6 was significantly higher in severe patients (SMD = 1.16; 95% CI = 0.69­1.63) with moderately high pooled sensitivity (79%; 95% CI = 61­91%) and specificity (86%; 95% CI = 72­95%). Conclusion: High serum KL-6 may depict more severe lung injury in COVID-19 patients with moderately high sensitivity and specificity.