Identification of biomarkers for the early detection of non-small cell lung cancer: a systematic review and meta-analysis.

Lung cancer (LC) causes few symptoms in the earliest stages, leading to one of the highest mortality rates among cancers. Low-dose computerised tomography (LDCT) is used to screen high-risk individuals, reducing the mortality rate by 20%. However, LDCT results in a high number of false positives and is associated with unnecessary follow-up and cost. Biomarkers with high sensitivities and specificities could assist in the early detection of LC, especially in patients with high-risk features. Carcinoembryonic antigen (CEA), cytokeratin 19 fragments and cancer antigen 125 have been found to be highly expressed during the later stages of LC but have low sensitivity in the earliest stages. We determined the best biomarkers for the early diagnosis of LC, using a systematic review of eight databases. We identified 98 articles that focussed on the identification and assessment of diagnostic biomarkers and achieved a pooled area under curve of 0.85 (95% CI 0.82-0.088), indicating that the diagnostic performance of these biomarkers when combined was excellent. Of the studies, 30 focussed on single/antigen panels, 22 on autoantibodies, 31 on miRNA and RNA panels, and 15 suggested the use of circulating DNA combined with CEA or neuron-specific enolase (NSE) for early LC detection. Verification of blood biomarkers with high sensitivities (Ciz1, exoGCC2, ITGA2B), high specificities (CYFR21-1, antiHE4, OPNV) or both (HSP90α, CEA) along with miR-15b and miR-27b/miR-21 from sputum may improve early LC detection. Further assessment is needed using appropriate sample sizes, control groups that include patients with non-malignant conditions, and standardised cut-off levels for each biomarker.

Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis.

Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. Objective: The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. Methods: This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Results: Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. Conclusion: The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.

Os anticolinérgicos (ACs) estão entre os medicamentos mais prescritos. Investigar os domínios cognitivos prejudicados devido ao uso individual de ACs está associado a achados controversos. Objetivo: Investigar os efeitos de ACs individuais em diferentes aspectos da função cognitiva, com base em estudos de ensaios clínicos. Métodos: Esta revisão sistemática foi realizada em acordo com a declaração PRISMA. Uma busca sistemática foi realizada nos bancos de dados Embase, PubMed, Cochrane Library, Scopus e Web of Science. O risco de viés (risk of bias - RoB) foi avaliado pelas listas de verificação do Joanna Briggs Institute e a meta-análise foi realizada através do software CMA. Resultados: Foram incluídos 138 estudos dos 3.026 resultados da pesquisa. Trinta e oito estudos que avaliam os impactos cognitivos da escopolamina foram incluídos na meta-análise. Os estudos incluídos relataram efeitos cognitivos de escopolamina, mecamilamina, atropina, biperideno, oxibutinina, triexifenidil, benzhexol, diciclomina; no entanto, glicopirrolato, tróspio, tolterodina, darifenacina, fesoterodina, tiotrópio e ipratrópio não foram associados ao declínio cognitivo. Com base nas meta-análises, a escopolamina foi associada a reconhecimento reduzido (DPM -1,84; IC95% -2,48 a -1,21; p<0,01), recordação imediata (DPM -1,82; IC95% -2,35 a -1,30; p<0,01), correspondência com a amostra (DPM -1,76; IC95% -2,57 a -0,96; p<0,01), recordação atrasada (DPM -1,54; IC95% -1,97 a -1,10; p <0,01), tarefas de memória complexas (DPM -1,31; IC95% -1,78 a -0,84; p<0,01), recordação livre (DPM -1,18; IC95% -1,63 a -0,73; p<0,01), função cognitiva (DPM -0,95; IC95% -1,46 a -0,44; p<0,01), atenção (DPM -0,85; IC95% -1,38 a -0,33; p<0,01) e amplitude de memória de dígitos (DPM -0,65; IC95% -1,21 a -0,10; p=0,02). Houve um alto RoB em nosso estudo, especialmente quanto aos possíveis confundidores. Conclusão: As limitações deste estudo sugerem a necessidade de estudos mais bem delineados e com maior duração de acompanhamento sobre o tema para alcançar evidências mais confiáveis.

Postesophagectomy chylothorax: a review of the risk factors, diagnosis, and management.

Chylothorax is a crucial postoperative complication of esophagectomy. Characterized by the leakage of chyle and lymphatic fluid through the thoracic duct, chylothorax could result in pleural effusion, respiratory distress, shortness of breath, cardiac arrhythmia, electrolyte imbalance, and malnutrition. Postesophagectomy chylothorax is associated with high morbidity and mortality, and its diagnosis and management require prompt and accurate identification of risk factors and treatment strategies. A variety of strategies are available to treat postesophagectomy chylothorax, ranging from conservative management to pharmacological, lymphangiographic, and surgical treatments. This study reviews the physio-anatomical basis, disease presentation, diagnostic methods, risk factors, and management options for postesophageal chylothorax, filling the literature gap, and highlighting the importance of early recognition and timely intervention in improving patient outcomes.

Upper lip bite test compared to modified Mallampati test in predicting difficult airway in obstetrics: A prospective observational study.

Difficult airway and intubation can have dangerous sequela for patients if not managed promptly. This issue is even more challenging among obstetric patients. Several studies have aimed to determine whether the test to predict a difficult airway or difficult intubation, is higher in accuracy. This study aims to compare the upper lip bite test with the modified Mallampati test in predicting difficult airway among obstetric patients. During this prospective observational study, 184 adult pregnant women, with ASA physical status of II, were enrolled. Difficult intubations of Cormack-Lehane grade III and IV were defined as difficult airways and difficult intubation in this study. Upper lip bite test, modified Mallampati test, thyromental distance and sternomental distance were noted for all patients. Modified Mallampati test, upper lip bite test and sternomental distance had highest specificity. Based on regression analysis, body mass index and Cormack-Lehane grade have a significant association. Modified Mallampati test was the most accurate test for predicting difficult airway. The best cut-off points of thyromental distance and sternomental distance in our study were 5cm and 15cm, respectively, by receiver operating characteristic curve analysis. Based on the results of the present study, it can be concluded that in the obstetric population, modified Mallampati test is practically the best test for predicting difficult airway. However, combining this test with upper lip bite test, thyromental distance and sternomental distance might result in better diagnostic accuracy.

Metformin: new applications for an old drug.

Metformin is a biguanide, evolved as one of the most widely used medicines. The applications of this component include but are not limited to reducing blood glucose, weight loss, and polycystic ovary syndrome. Studies about other probable indications have emerged, indicating that this agent can also be utilized for other purposes. In this review, applications of metformin are noticed based on the current evidence. Metformin commonly is used as an off-label drug in non-alcoholic fatty liver disease (NAFLD), but it worsens inflammation and should not be used for this purpose, according to the latest research. Metformin decreased the risk of death in patients with liver cirrhosis. It is an effective agent in the prevention and improvement of survival in patients suffering hepatocellular carcinoma. There is evidence of the beneficial effects of metformin in colorectal cancer, early-stage prostate cancer, breast cancer, urothelial cancer, blood cancer, melanoma, and bone cancer, suggesting metformin as a potent anti-tumor agent. Metformin shows neuroprotective effects and provides a potential therapeutic benefit for mild cognitive impairment and Alzheimer's disease (AD). It also has been shown to improve mental function and reduce the incidence of dementia. Another condition that metformin has been shown to slow the progression of is Duchenne muscular dystrophy. Regarding infectious diseases, tuberculosis (TB) and coronavirus disease (COVID-19) are among the conditions suggested to be affected by metformin. The beneficial effects of metformin in cardiovascular diseases were also reported in the literature. Concerning renal function, studies showed that daily oral administration of metformin could ameliorate kidney fibrosis and normalize kidney structure and function. This study reviewed the clinical and preclinical evidence about the possible benefits of metformin based on recent studies. Numerous questions like whether these probable indications of metformin can be observed in non-diabetics, need to be described by future basic experiments and clinical studies.

Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis / Efeitos cognitivos de drogas anticolinérgicas individuais: uma revisão sistemática e meta-análise

ABSTRACT. Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. Objective: The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. Methods: This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Results: Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. Conclusion: The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.

RESUMO. Os anticolinérgicos (ACs) estão entre os medicamentos mais prescritos. Investigar os domínios cognitivos prejudicados devido ao uso individual de ACs está associado a achados controversos. Objetivo: Investigar os efeitos de ACs individuais em diferentes aspectos da função cognitiva, com base em estudos de ensaios clínicos. Métodos: Esta revisão sistemática foi realizada em acordo com a declaração PRISMA. Uma busca sistemática foi realizada nos bancos de dados Embase, PubMed, Cochrane Library, Scopus e Web of Science. O risco de viés (risk of bias - RoB) foi avaliado pelas listas de verificação do Joanna Briggs Institute e a meta-análise foi realizada através do software CMA. Resultados: Foram incluídos 138 estudos dos 3.026 resultados da pesquisa. Trinta e oito estudos que avaliam os impactos cognitivos da escopolamina foram incluídos na meta-análise. Os estudos incluídos relataram efeitos cognitivos de escopolamina, mecamilamina, atropina, biperideno, oxibutinina, triexifenidil, benzhexol, diciclomina; no entanto, glicopirrolato, tróspio, tolterodina, darifenacina, fesoterodina, tiotrópio e ipratrópio não foram associados ao declínio cognitivo. Com base nas meta-análises, a escopolamina foi associada a reconhecimento reduzido (DPM -1,84; IC95% -2,48 a -1,21; p<0,01), recordação imediata (DPM -1,82; IC95% -2,35 a -1,30; p<0,01), correspondência com a amostra (DPM -1,76; IC95% -2,57 a -0,96; p<0,01), recordação atrasada (DPM -1,54; IC95% -1,97 a -1,10; p <0,01), tarefas de memória complexas (DPM -1,31; IC95% -1,78 a -0,84; p<0,01), recordação livre (DPM -1,18; IC95% -1,63 a -0,73; p<0,01), função cognitiva (DPM -0,95; IC95% -1,46 a -0,44; p<0,01), atenção (DPM -0,85; IC95% -1,38 a -0,33; p<0,01) e amplitude de memória de dígitos (DPM -0,65; IC95% -1,21 a -0,10; p=0,02). Houve um alto RoB em nosso estudo, especialmente quanto aos possíveis confundidores. Conclusão: As limitações deste estudo sugerem a necessidade de estudos mais bem delineados e com maior duração de acompanhamento sobre o tema para alcançar evidências mais confiáveis.

Prognostic value of National Early Warning Score and Modified Early Warning Score on intensive care unit readmission and mortality: A prospective observational study.

Background: Modified Early Warning Score (MEWS) and National Early Warning Score (NEWS) are widely used in predicting the mortality and intensive care unit (ICU) admission of critically ill patients. This study was conducted to evaluate and compare the prognostic value of NEWS and MEWS for predicting ICU readmission, mortality, and related outcomes in critically ill patients at the time of ICU discharge. Methods: This multicenter, prospective, observational study was conducted over a year, from April 2019 to March 2020, in the general ICUs of two university-affiliated hospitals in Northwest Iran. MEWS and NEWS were compared based on the patients' outcomes (including mortality, ICU readmission, time to readmission, discharge type, mechanical ventilation (MV), MV duration, and multiple organ failure after readmission) using the univariable and multivariable binary logistic regression. The receiver operating characteristic (ROC) curve was used to determine the outcome predictability of MEWS and NEWS. Results: A total of 410 ICU patients were enrolled in this study. According to multivariable logistic regression analysis, both MEWS and NEWS were predictors of ICU readmission, time to readmission, MV status after readmission, MV duration, and multiple organ failure after readmission. The area under the ROC curve (AUC) for predicting mortality was 0.91 (95% CI = 0.88-0.94, P < 0.0001) for the NEWS and 0.88 (95% CI = 0.84-0.91, P < 0.0001) for the MEWS. There was no significant difference between the AUC of the NEWS and the MEWS for predicting mortality (P = 0.082). However, for ICU readmission (0.84 vs. 0.71), time to readmission (0.82 vs. 0.67), MV after readmission (0.83 vs. 0.72), MV duration (0.81 vs. 0.67), and multiple organ failure (0.833 vs. 0.710), the AUCs of MEWS were significantly greater (P < 0.001). Conclusion: National Early Warning Score and MEWS values of >4 demonstrated high sensitivity and specificity in identifying the risk of mortality for the patients' discharge from ICU. However, we found that the MEWS showed superiority over the NEWS score in predicting other outcomes. Eventually, MEWS could be considered an efficient prediction score for morbidity and mortality of critically ill patients.

Is COVID-19 really a geriatric syndrome?

Geriatric syndromes are a group of medical conditions, such as cognitive impairment, delirium, frailty, dizziness, syncope, and incontinence, associated with age increase. Many studies have reported a higher mortality rate for older COVID-19 patients, which could be explained by the complications of COVID-19, including the components of geriatric syndromes. We read with great interest the paper "Prevalence of unwillingness and uncertainty to vaccinate against COVID-19 in older people: A systematic review and meta-analysis" by Nicola Veronese et al. Their valuable work determines how uncertainty and unwillingness towards receiving the COVID-19 vaccine are more prevalent among older adults and how this hesitancy could affect vaccine uptake, and ultimately, the mortality rate. Regarding this paper, we wish to address some points.

Impact of Body Mass Index on the Mortality of Critically Ill Patients Admitted to the Intensive Care Unit: An Observational Study.

BACKGROUND: Obesity is a severe multifactorial disorder that carries high morbidity and mortality. OBJECTIVES: This study aimed to evaluate the possible association between body mass index (BMI) and mortality in patients admitted to intensive care units (ICU). METHODS: In this cross-sectional study, all patients admitted to the ICU were studied. The demographic characteristics, ICU, and hospital length of stay, organ failure, mortality, duration of mechanical ventilation, the occurrence of nosocomial infection, and type of admission were recorded for all patients. Patients were categorized based on their BMI. RESULTS: In total, 502 patients were studied who 53.2% of them were male. Most of the death (28.6%) were recorded in the obesity class II patients, while the lowest rate (3.9%) was for the normal-weight patients (P value < 0.001). The APACHE II and waist circumference had a statistically significant association with the mortality rate (P value < 0.001). After adjusting for age and gender, a significant association was found between waist circumference and mortality rate (OR = 1.15, 95% CI = 1.03 - 1.29; P value = 0.014), APACHE II score, and mortality rate (OR = 2.79, 95% CI = 1.91 - 4.07, P value < 0.001); but there was no significant association between BMI and mortality rate. CONCLUSIONS: This study demonstrated that BMI is associated with an increased risk of mortality, regardless of age and gender. However, after adjusting for age and gender as confounding factors, BMI didn't have a significant effect on mortality, while the APACHE II score and waist circumference affected the mortality rate.

Kawasaki or Kawasaki-like disease? A debate on COVID-19 infection in children.

Kawasaki disease (KD) is an inflammatory syndrome which is generally observed among children. Considering the significant number of COVID-19-positive children presenting with the manifestations of typical/atypical KD, it has been mentioned as a possible complication of COVID-19 infection among the children. However, many of the reported cases do not completely fill the clinical diagnostic criteria, which has made some researchers use the term "Kawasaki-like disease" instead of KD for this state. The current manuscript aims to review the key studies in the field, address the ongoing conflict, and indicate the objective requirements of the further studies.