Invasive Surgery For Lung Cancer Research Articles

Preoperative Exercise Training Decreases Complications of Minimally Invasive Lung Cancer Surgery- A Randomized Controlled Trial

ObjectiveLimited evidence exists regarding the efficacy of preoperative exercise (PE) in reducing short-term complications after minimally invasive surgery in patients with non-small cell lung cancer (NSCLC). This study aims to investigate the impact of PE on short-term complications following minimally invasive lung resection. MethodsIn this prospective, open-label, randomized (1:1) controlled trial at Xiangya Hospital, China (Sep 2020-Feb 2022), patients were randomly assigned to a PE group with 16-day alternate supervised exercise or a control. The primary outcome assessed was short-term postoperative complications, with a follow-up period of 30 days post-surgery. ResultsA total of 124 patients were recruited (PE group n=62; control n=62). Finally, 101 patients (PE group; n=51 and control; n=50) with a median age of 56 years (interquartile range, 50–62 years) completed the study. Compared with the control, the PE group showed fewer postoperative complications (PE:3/51 vs. Control 10/50; OR [95% CI], 0.17 [0.04 to 0.86], P=0.03) and shorter hospital stays (mean difference [95% CI], -2 [-3 to -1], P=0.01). PE significantly improved depression, stress, functional capacity, and quality of life (all P<0.05) before surgery. Furthermore, PE demonstrated a significantly lower minimum blood pressure during surgery, lower increases body temperature on day 2 after surgery, neutrophil-to-lymphocyte ratio, and neutrophil count after surgery (all P<0.05). Exploratory research on lung tissue RNA sequencing (5 in each group) showed downregulation of the tumor necrosis factor signaling pathway in the PE group compared with control. ConclusionsPreoperative exercise training decreased short-term postoperative complications in patients with NSCLC.

Meta-lasso: new insight on infection prediction after minimally invasive surgery.

Surgical site infection (SSI) after minimally invasive lung cancer surgery constitutes an important factor influencing the direct and indirect economic implications, patient prognosis, and the 5-year survival rate for early-stage lung cancer patients. In the realm of predictive healthcare, machine learning algorithms have been instrumental in anticipating various surgical outcomes, including SSI. However, accurately predicting infection after minimally invasive surgery remains a clinical challenge due to the multitude of physiological and surgical factors associated with it. Furthermore, clinical patient data, in addition to being high-dimensional, often exists the long-tail problem, posing difficulties for traditional machine learning algorithms in effectively processing such data. Based on this insight, we propose a novel approach called meta-lasso for infection prediction following minimally invasive surgery. Our approach leverages the sparse learning algorithm lasso regression to select informative features and introduces a meta-learning framework to mitigate bias towards the dominant class. We conducted a retrospective cohort study on patients who had undergone minimally invasive surgery for lung cancer at Shanghai Chest Hospital between 2018 and 2020. The evaluation encompassed key performance metrics, including sensitivity, specificity, precision (PPV), negative predictive value (NPV), and accuracy. Our approach has surpassed the performance of logistic regression, random forest, Naive Bayes classifier, gradient boosting decision tree, ANN, and lasso regression, with sensitivity at 0.798, specificity at 0.779, precision at 0.789, NPV at 0.798, and accuracy at 0.788 and has greatly improved the classification performance of the inferior class.

Retracted: Medical Data Analysis of CYP1B1 Gene Polymorphism and Clinical Prognosis of Minimally Invasive Surgery for Lung Cancer

Retracted: Medical Data Analysis of CYP1B1 Gene Polymorphism and Clinical Prognosis of Minimally Invasive Surgery for Lung Cancer

Retracted: CYP1B1 Gene Polymorphism Based on Health Monitoring and Nursing Methods after Minimally Invasive Surgery for Lung Cancer.

[This retracts the article DOI: 10.1155/2022/7042014.].

Medical Data Analysis of CYP1B1 Gene Polymorphism and Clinical Prognosis of Minimally Invasive Surgery for Lung Cancer.

To address the issue of genetic mutations in medical records, clinical studies on minimally invasive surgery for breast cancer have been proposed. The CYP1B1 gene is mainly a single-nucleotide mutation, which affects the enzymatic reaction related to carcinogens and causes the susceptibility differences of different individuals. First, the survival rate and other factors influencing the estimation of 120 leukemia patients were examined with the help of various medical records by establishing an organization for auxiliary diagnosis of lung cancer based on expertise. Secondly, through the treatment of 120 leukemia patients after minor surgery, the average life expectancy of 120 patients was 19 months, the one-year survival rate was 74.61%, and the two-year survival rate was 32.70%. Currently, there are more than 160 cases of CYP1B1 discovered. In recent years, people have gradually entered into in-depth research on the correlation between genes and lung cancer, which is of great significance to the treatment and research of lung cancer. An analysis showed patients' age, stage, whether they would work, whether radiation therapy and antibiotics were offered, and so on. s has a direct impact on patient survival, and many tests have shown that the patient's age, stage, whether it will work, and whether fire radiation and drug therapy are provided are important interventions for patients with anemia. Finally, in patients with leukemia, especially during the restricted period, combined treatment with a physician, radiologist, and surgeon should be initiated as soon as possible. For a wide range of disease, depending on the use of chemotherapy, local metastasis with antibiotics can improve the disease. After success, it is more beneficial to choose second-line treatment.

CYP1B1 Gene Polymorphism Based on Health Monitoring and Nursing Methods after Minimally Invasive Surgery for Lung Cancer.

The rapid development of science and technology has become an indispensable part of human life. Minimally invasive lung cancer surgery, that is, thoracoscopic surgery and da Vinci robotic surgery, has many advantages over previous surgeries, there is no need to make a large incision in the chest, the patient after such surgery, and recovery is also better and can also reduce the incision of the operation. Therefore, with the rapid development of science and technology today, how to detect changes in patients' health and establish an intelligent health monitoring system has become a development trend. This paper proposes to apply health monitoring in CYP1B1 gene polymorphism and nursing after clinical treatment of minimally invasive lung cancer surgery, after analyzing the society's demand for real-time health monitoring in this paper. It also studies the health monitoring system based on the advantages of smart phones. The system is suitable for the Android operating system and can monitor the temperature, weight, and other data of the human body. The experimental results show that the data value of the information displayed by the android software has a high degree of matching with the measured value, which basically keeps floating around 80, and the data consistency is strong.

Long-Term Survival Following Minimally Invasive Lung Cancer Surgery: Comparing Robotic-Assisted and Video-Assisted Surgery.

Simple SummaryVideo-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS) are known to be safe and efficient surgical procedures to treat lung cancer. Both VATS and RATS allow anatomical resection associated with radical lymph node dissection. However, RATS, unlike VATS, allows the thoracic surgeon to mimic an open approach and to perform lung resection. We hypothesized that the technical advantages of RATS, compared with VATS, would allow more precise resection, with “better lymph node dissection” which could increase survival compared to VATS. Nevertheless, VATS, and RATS nodal up-staging are still debated, with conflicting results and in our study, as well as in the medical literature, RATS failed to show its superiority over VATS in resectable non-small cell lung cancer.Background: Nowadays, video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS) are known to be safe and efficient surgical procedures to treat early-stage non-small cell lung cancer (NSCLC). We assessed whether RATS increased disease-free survival (DFS) compared with VATS for lobectomy and segmentectomy. Methods: This retrospective cohort study included patients treated for resectable NSCLC performed by RATS or VATS, in our tertiary care center from 2012 to 2019. Patients’ data were prospectively recorded and reviewed in the French EPITHOR database. Primary outcomes were 5-year DFS for lobectomy and 3-year DFS for segmentectomy, compared by propensity-score adjusted difference of Kaplan–Meier estimates. Results: Among 844 lung resections, 436 VATS and 234 RATS lobectomies and 46 VATS and 128 RATS segmentectomies were performed. For lobectomy, the adjusted 5-year DFS was 60.9% (95% confidence interval (CI) 52.9–68.8%) for VATS and 52.7% (95%CI 41.7–63.7%) for RATS, with a difference estimated at −8.3% (−22.2–+4.9%, p = 0.24). For segmentectomy, the adjusted 3-year DFS was 84.6% (95%CI 69.8–99.0%) for VATS and 72.9% (95%CI 50.6–92.4%) for RATS, with a difference estimated at −11.7% (−38.7–+7.8%, p = 0.21). Conclusions: RATS failed to show its superiority over VATS for resectable NSCLC.

A Delphi Consensus report from the "Prolonged Air Leak: A Survey" study group on prevention and management of postoperative air leaks after minimally invasive anatomical resections.

This study reports the results of an international expert consensus process evaluating the assessment of intraoperative air leaks (IAL) and treatment of postoperative prolonged air leaks (PAL) utilizing a Delphi process, with the aim of helping standardization and improving practice. A panel of 45 questions was developed and submitted to an international working group of experts in minimally invasive lung cancer surgery. Modified Delphi methodology was used to review responses, including 3 rounds of voting. The consensus was defined a priori as >50% agreement among the experts. Clinical practice standards were graded as recommended or highly recommended if 50-74% or >75% of the experts reached an agreement, respectively. A total of 32 experts from 18 countries completed the questionnaires in all 3 rounds. Respondents agreed that PAL are defined as >5 days and that current risk models are rarely used. The consensus was reached in 33/45 issues (73.3%). IAL were classified as mild (<100 ml/min; 81%), moderate (100-400 ml/min; 71%) and severe (>400 ml/min; 74%). If mild IAL are detected, 68% do not treat; if moderate, consensus was not; if severe, 90% favoured treatment. This expert consensus working group reached an agreement on the majority of issues regarding the detection and management of IAL and PAL. In the absence of prospective, randomized evidence supporting most of these clinical decisions, this document may serve as a guideline to reduce practice variation.

Minimally Invasive Surgery for Lung Cancer Following Neoadjuvant Therapy in the United States.

Introduction: Pulmonary resections following neoadjuvant therapy (NT) can be technically demanding. There is a paucity of data regarding the use of minimally invasive surgery (MIS) approaches in that setting on the National level. In this study, we explored the trends of using MIS approaches following NT and its associated outcomes. Methods: The study included all adult patients with non-small cell lung cancer who underwent pulmonary resection following NT between 2010 and 2016. Propensity score (PS) matching (MIS versus open) was performed and the perioperative outcomes were compared. Results: The study included 11,287 patients who underwent pulomonary resection after NT. The percentage of patients undergoing MIS lung resection and the number of hospitals performing one or more MIS increased from 19% and 166 (2010) to 41% and 305 (2016), respectively. When compared with thoracotomy, MIS lung resections were more frequently performed in academic centers in patients with higher income (P < .001). In PS matched groups, the use of MIS was associated with shorter hospital length of stay (5 days versus 6 days; P < .001), compared with open approach. However, there were no differences between the two groups in readmission rate (P = .513), or 30-/90-day mortality (P = .145/.685). In multivariable regression analysis, MIS approach was not associated with worse long-term, all-cause, survival (confidence interval: 0.91-1.09). Conclusion: The use of MIS approaches after NT increased significantly over the study period and was associated with perioperative outcomes and long-term survival comparable to those noted with the open approach.

Safety profile of preoperative administration of low-molecular-weight heparin on minimally invasive lung cancer surgery: a randomized controlled trial

BackgroundVenous thromboembolism remains a common but preventable complication for cancerous lung surgical patients. Current guidelines recommend thromboprophylaxis for lung patients at high risk of thrombosis, while a consensus about specific administration time is not reached. This study was designed to investigate the safety profile of preoperative administration of low-molecular-weight-heparin (LMWH) for lung cancer patients.MethodsFrom July 2017 to June 2018, patients prepared to undergo lung cancer surgery were randomly divided into the preoperative LMWH-administration group (PRL) for 4000 IU per day and the postoperative LMWH-administration group (POL) with same dosage, all the patients received thromboprophylaxis until discharge. Baseline characteristics including demographics and preoperative coagulation parameters were analyzed, while the endpoints included postoperative coagulation parameters, postoperative drainage data, hematologic data, intraoperative bleeding volume and reoperation rate.ResultsA total of 246 patients were collected in this RCT, 34 patients were excluded according to exclusion criterion, 101 patients were assigned to PRL group and 111 patients belonged to POL group for analysis finally. The baseline characteristic and preoperative coagulation parameters were all comparable except the PRL group cost more operation time (p = 0.008) and preoperative administration duration was significantly longer (p < 0.001). The endpoints including postoperative day 1 coagulation parameters, mean and total drainage volume, drainage duration, intraoperative bleeding volume and reoperation rate were all similar between the two groups. Moreover, coagulation parameters for postoperative day 3 between the two groups demonstrated no difference.ConclusionPreoperative administration of low-molecular-weight-heparin demonstrated safety and feasibility for lung cancer patients intended to receive minimally invasive surgery.Trial registration: ChiCTR2000040547 (www.chictr.org.cn), 2020/12/1, retrospectively registered.

Uptake and survival effects of minimally invasive surgery for lung cancer: A population-based study

IntroductionDespite growing evidence supporting the safety of minimally invasive surgery (MIS) in the treatment of lung cancer, its uptake is still variable and its outcomes debated. This study examines the factors associated with MIS uptake and its effects on survival in patients with non-small cell lung cancer (NSCLC). MethodsAll patients in the Canadian province of Ontario with early stage NSCLC (stage I/II) from 2007 to 2017 were included. A logistic regression identified the predictors of MIS uptake, and a flexible parametric model was used to estimate survival rates based on MIS versus open resection. ResultsIn total, 8,988 patients underwent surgical resection; 53.6% had MIS. Year of diagnosis was associated with MIS uptake (OR = 1.33, p < 0.001); patients in later years were more likely to receive MIS. Rurality was a significant predictor of MIS, though distance from nearest regional cancer center did not predict MIS utilization. Patients with stage II disease were less likely to receive MIS compared to those with stage I disease (OR = 0.44, p < 0.001). MIS had a significantly higher 5-year survival compared to open resection for stage I and II disease. Patients >70 years had the greatest 5-year survival benefit from MIS. ConclusionsWe observed a substantial long-term survival benefit in patients undergoing MIS for early stage NSCLC. This difference was most pronounced in the oldest age group. These findings support the use of MIS in the treatment of lung cancer and challenge the notion that MIS compromises oncologic outcomes.

Confocal laser microscopy without fluorescent dye in minimal-invasive thoracic surgery: an ex-vivo pilot study in lung cancer.

Cancer will be the leading cause of death in a few decades. In line with minimal invasive lung cancer surgery, surgeons loose most of their tactile tissue information and need an additional tool of intraoperative tissue navigation during surgery. Confocal laser microscopy is a well-established method of tissue investigation. In this ex-vivo pilot study, we evaluated an endoscopic confocal laser microscope (eCLM) that does not need any fluorescent dye as a diagnostic tool in non-malignant and malignant pulmonary tissue and distal stapler resection margins, respectively. In seven cases, an eCLM was used for examining pulmonary tissue ex-vivo. Images of non-malignant and non-small cell lung cancer tissue and distal stapler resection margins were characterized in terms of specific signal-patterns. No fluorescent dye was used. Correlations to findings in conventional histology were systematically recorded and described. Healthy lung tissue showed hyperreflectoric alveolar walls with dark alveolar spaces. Hyperreflective nets indicated the tumor stroma; whereas the hyperreflective areas indicated the tumor cell clusters. Compared to adenocarcinoma tissue, tissue from squamous cell carcinoma showed more distinctive hyperreflective stroma nets. eCLM characteristics seen in non-malignant and malignant tissue were also visible in distal stapler resection margins and so therefore it was feasible to distinguish between healthy lung tissue and lung cancer. This pilot study shows that the assessment of pulmonary tissue with this eCLM for minimally invasive surgical approach without any fluorescent dye is feasible. It enables to differentiate between benign and malignant tissue in pulmonary specimen by easy to evaluate and reproducible parameters.

Association Between Patient Physical Function and Length of Stay After Thoracoscopic Lung Cancer Surgery

Patient-reported outcomes (PRO) are an ideal method for measuring patient functional status. We sought to evaluate whether preoperative PRO were associated with resource utilization. We hypothesize that higher preoperative physical function PRO scores, measured via the NIH-sponsored Patient Reported Outcome Measurement Information System (PROMIS), are associated with shorter length of stay (LOS). Preoperative physical function scores were obtained using NIH PROMIS in a prospective observational study of patients undergoing minimally invasive surgery for lung cancer. Poisson regression models were constructed to estimate the association between the length of stay and PROMIS physical function T-score, adjusting for extent of resection, age, gender, and race. Due to the significant interaction between postoperative complications and physical function T-score, the relationship between physical function and LOS was described separately for each complication status. A total of 123 patients were included; 88 lobectomy, 35 sublobar resections. Mean age was 67 years, 35% were male, 65% were Caucasian. Among patients who had a postoperative complication, a lower preoperative physical function T-score was associated with progressively increasing LOS (P  value = 0.006). In particular, LOS decreased by 18% for every 10-point increase in physical function T-score. Among patients without complications, T-score was not associated with LOS (P = 0.86). Preoperative physical function measured via PRO identifies patients who are at risk for longer LOS following thoracoscopic lung cancer surgery. In addition to its utility for preoperative counseling and planning, these data may be useful in identifying patients who may benefit from risk-reduction measures.

Preoperative Lung Function Is Associated With Patient-Reported Outcomes After Lung Cancer Surgery

Patient quality of life (QOL) is a critical outcomes measure in lung cancer surgery. Patient-reported outcomes (PROs) provide valuable insight into the patient experience and allow measurement of preoperative and postoperative QOL. Our objective was to determine which clinical factors predict differences in QOL, as measured by patient-reported physical function and pain intensity among patients undergoing minimally invasive lung cancer surgery. PRO surveys assessing physical function and pain intensity were conducted using instruments from the National Institutes of Health Patient-Reported Outcomes Measurement Information System. PRO surveys were administered to patients undergoing minimally invasive lung cancer resections at preoperative, 1-month, and 6-month postoperative time points, in an academic institution. Linear mixed-effects regression models were constructed to assess the association between clinical variables on PRO scores over time. A total of 123 patients underwent a thoracoscopic lung resection for cancer. Mean age of the cohort was 67 ± 9.6 years, 43% were male, and 80% were White. When comparing clinical variables with PRO scores after surgery, lower diffusing capacity of the lungs for carbon monoxide (Dlco) was associated with significantly worse physical function (P < .01) and greater pain intensity scores (P < .01) at 6 months, with no differences identified at 1 month. No other studied clinical factor was associated with significant differences in PRO scores. Low preoperative Dlco was associated with significant decreases in PRO after minimally invasive lung cancer surgery. Dlco may be of utility in identifying patients who experience greater decline in QOL after surgery and for guiding surgical decision making.

A commentary on “albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database” (International Journal of Surgery 2019; 59: 32–42)

A commentary on “albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database” (International Journal of Surgery 2019; 59: 32–42)

Efficacy of transcutaneous electrical acupoint stimulation combined with general anesthesia for sedation and postoperative analgesia in minimally invasive lung cancer surgery: A randomized, double-blind, placebo-controlled trial.

BackgroundMultimodal opioid‐sparing analgesia is a key component of an enhanced recovery pathway after surgery that aims to improve postoperative recovery. Transcutaneous electrical acupoint stimulation (TEAS) is assumed to alleviate pain and anxiety and to modify the autonomic nervous system. This study aimed to determine the efficacy of TEAS for sedation and postoperative analgesia in lung cancer patients undergoing thoracoscopic pulmonary resection.MethodsA total of 80 patients were randomized into two groups: the TEAS group and the sham TEAS combined with general anesthesia group. Postoperative pain levels at six, 24, 48 hours, and one month after surgery were measured using the visual analogue scale (VAS). Bispectral index (BIS) score during the TEAS prior to anesthetic induction, Observer's Assessment of Alertness/Sedation (OAAS) score, sufentanil consumption during postoperative patient‐controlled intravenous analgesia (PCIA), number of total and effective attempts of PCIA pump use, and incidence of postoperative nausea and vomiting were recorded and analyzed statistically.ResultsPatients in the TEAS group had significantly lower VAS scores at six, 24, and 48 hours after surgery (P < 0.01); lower BIS scores at 10, 20, and 30 minutes before induction (P < 0.01); lower levels of postoperative sufentanil consumption; lower number of PCIA attempts and effective rates (P < 0.01); lower incidences of nausea at 0, six, 24, and 48 hours; and lower incidence of vomiting at 24 hours after surgery (P < 0.05). The postoperative OAAS scores were similar between the groups.ConclusionsTEAS could be a feasible approach for sedation and postoperative analgesia in thoracoscopic pulmonary resection.

P2.17-24 Minimally Invasive Surgery for Lung Cancer Improves Short Term Outcomes in Patients with History of Head and Neck Carcinoma

P2.17-24 Minimally Invasive Surgery for Lung Cancer Improves Short Term Outcomes in Patients with History of Head and Neck Carcinoma

Albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database

Albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database

Albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database

To evaluate prognostic significance of albumin-to-alkaline phosphatase ratio (AAPR) for patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC) by a propensity score-matching (PSM) analysis. This PSM study was conducted on the prospectively-maintained database in our institution between December 2013 and March 2015. Overall survival analyses and further subgroup analyses were both performed to distinguish the differences in postoperative survival between patients stratified by an optimal cutoff of AAPR. Multivariable Cox proportional hazards regression models were established to determine the independent prognostic factors. There were 390 patients with operable NSCLCs included. An AAPR of 0.57 was identified as the optimal cutoff regarding to postoperative survival. Both overall survival (OS) and disease-free survival (DFS) in patients with AAPR≤0.57 were significantly shortened compared to those in patient with AAPR>0.57 (Log-rank P < 0.001). Patients with AAPR≤0.57 had significantly lower rates of OS and DFS than those of patients with AAPR>0.57 (P < 0.001). These differences still remained significant after subgroup analyses and PSM analyses. Multivariate analyses on the entire cohort and the PSM cohort commonly indicated that low preoperative AAPR could be an independent prognostic factor for unfavorable OS and DFS of resected NSCLCs. AAPR can serve as a novel risk stratification tool to refine prognostic prediction for surgical NSCLC. It may help surgeons to screen high-surgical-risk patients and further formulate individualized treatment schemes.

Thoracoscopic surgery for lung cancer is associated with improved survival and shortened admission length: a nationwide propensity-matched study.

Population-based studies comparing long-term survival after minimally invasive and open surgery for lung cancer are lacking. The aim of this study was to compare long-term survival rates between minimally invasive [video-assisted thoracoscopic surgery (VATS)] and open surgery for lung cancer in an unselected nationwide setting. Patients undergoing minimally invasive (n = 710) or open (n = 2814) lung resection for lung cancer between 2004 and 2014 were identified from nationwide complete registries in Finland. Propensity score matching resulted in groups of 632 patients who had VATS and 632 who had a thoracotomy. The primary outcome was the 1-year survival rate. Secondary outcomes were 30-day, 90-day and 5-year survival rates and the length of surgical admission. Cox models were adjusted for sex, age, comorbidity, centre size, year of surgery, histological diagnosis, stage and adjuvant therapy. In the propensity-matched cohort, the 1-year survival rate was 90.8% [confidence interval (CI) 88.3-92.8%] after VATS and 87.1% (CI 84.3-89.6%) after open surgery. The 5-year survival rate in the propensity-matched cohort was 59.6% (CI 54.9-63.9%) after VATS and 53.3% (CI 48.6-57.7%) after open surgery. The 30-day mortality rates showed no differences between approaches, but the 90-day mortality rate was better after VATS when adjusted for patient-, tumour- and operation-specific features (hazard ratio 0.56, 95% CI 0.30-0.92; P = 0.024). According to this population-based nationwide study from Finland, minimally invasive surgery for lung cancer is associated with improved long- and short-term survival rates, supporting the use of VATS as a primary surgical method for treating lung cancer. Due to the complexity of confounding factors in this study, one should, however, interpret the results critically. Additional studies are needed.