Home Medicine The influence of smoking in minimally invasive spinal fusion surgery
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The influence of smoking in minimally invasive spinal fusion surgery

  • Wolfgang Senker EMAIL logo , Harald Stefanits , Matthias Gmeiner , Wolfgang Trutschnig , Christian Radl and Andreas Gruber
Published/Copyright: January 27, 2021

Abstract

Background

The impact of smoking on spinal surgery has been studied extensively, but few investigations have focused on minimally invasive surgery (MIS) of the spine and the difference between complication rates in smokers and non-smokers. We evaluated whether a history of at least one pack-year preoperatively could be used to predict adverse peri- and postoperative outcomes in patients undergoing minimally invasive fusion procedures of the lumbar spine. In a prospective study, we assessed the clinical effectiveness of MIS in an unselected population of 187 patients.

Methods

We evaluated perioperative and postoperative complication rates in MIS fusion techniques of the lumbar spine in smoking and non-smoking patients. MIS fusion was performed using interbody fusion procedures and/or posterolateral fusion alone.

Results

Smokers were significantly younger than non-smokers. We did not encounter infection at the site of surgery or severe wound healing disorder in smokers. We registered no difference between the smoking and non-smoking groups with regard to peri- or postoperative complication rate, blood loss, or length of stay in hospital. We found a significant influence of smoking (p = 0.049) on the overall perioperative complication rate.

Conclusion

MIS fusion techniques seem to be a suitable tool for treating degenerative spinal disorders in smokers.

1 Introduction

Smoking continues to contribute considerably to health problems across Europe. According to Eurostat, 19.2% of Europeans smoke on a daily basis, whereas 4.7% are occasional smokers. In the European Union (EU), one in four people (24.9%) aged 15 years or older smokes with a higher percentage of male smokers (28.7%) than female smokers (19.5%). Consequently, spine surgeons have to treat a sizable group of smoking patients. Moreover, smoking has been shown to have a harmful effect on bone healing. The literature shows that the rate of nonunion or pseudarthrosis after spinal fusion is higher in smokers than in non-smokers [1,2,3,4,5]. However, the distinct pathophysiologic mechanisms that lead to these differences are still unclear. The most commonly accepted theories hypothesize that a decrease in systemic bone mineral density, osteoblastic cellular metabolism, local blood flow, and angiogenesis may cause these differences [6]. Smokers are also significantly more likely to report less favorable clinical outcomes after spinal surgery. Furthermore, the literature shows that smokers suffer from postoperative infections more frequently than non-smokers do [3]. This study compares the perioperative complication rate, blood loss, and length of hospital stay of smoking and non-smoking patients who are undergoing minimally invasive fusion procedures of the lumbar spine. Data treating these specific topics, especially in minimally invasive surgery (MIS), are scarce.

2 Materials and methods

This study was approved by the ethics committee. We recruited 187 patients for this prospective investigation, of which 115 were female and 72 male. Written informed consent was obtained from all patients, and the study was registered at ClinicalTrials.gov (NCT01259960). We categorized patients as smokers (history of at least one pack-year) and non-smokers and further subdivided them according to age group. We split the data into two age groups (≤64 and ≥65).

2.1 Surgical technique

Revisions of the disc space and laminotomy for spinal stenosis were performed using the Quadrant Tubular Retractor System (Medtronic Inc., Memphis, TN, USA). After identifying the appropriate facet joint using fluoroscopy, an incision was made 1.5 cm off the midline. A tube was inserted subcutaneously and muscle tissue was sequentially dilated by creating a corridor to the facet joint in a fashion similar to that described by Foley and Smith [7]. Next, a tubular retractor was inserted. The facet joint and the yellow ligament were exposed. We used the percutaneous fusion system Sextant II or Longitude (both Medtronic Inc.) for posterolateral fusion. In 360° fusion cases, we performed a transforaminal lumbar interbody fusion (TLIF) procedure [8]. In spinal stenosis cases, the retractor was directed to the contralateral side of the spinal canal to perform a laminotomy (146 patients) [9].

2.2 Statistics

Statistical analyses were performed using the R package (npmv). We used the nonpartest [10] for testing the null hypothesis that the underlying distributions in the groups under investigation coincided. Whenever three groups were encountered, we used the standard three-sample test for equality of proportions. A linear dependence of variables was determined by Pearson’s correlation, whereas concordance was demonstrated by Spearman’s rank correlation. Statistical significance was assumed by a p-value of <0.05.

3 Results

The sample of 187 patients contained 18 male (25%) and 31 female (27%) smokers (for one patient, no information was available). The mean age of the total cohort was 64.27 years (range: 33–85 years), that of the smoker group was 53.27 years (49–74 years), and that of the non-smoker group was 68.10 years (41–85 years). The age distributions of smokers and non-smokers differ significantly (Figure 1). Going forward, we will refer to this fact as “smoking-age-bias.” Testing for equal age distribution in the smoking and the non-smoking groups using nonpartest [10] yields a p-value of 0 for the full sample, as well as for the male and the female subsamples. Consequently, any variable of interest that positively correlates with the “age” variable is likely to have lower correlation values in the smoker group than in the non-smoker group. Furthermore, we defined diabetes (DM, n = 34), coronary heart disease (CHD, n = 20), any other cardiac disease including atrial fibrillation (n = 9), and peripheral vascular disease (PAD, n = 7) as secondary diseases and looked at a possible statistical impact. Fifty-eight patients suffered from at least one secondary disease.

Figure 1 
               Number of female and male smokers (left and middle panels) and age distribution of smokers and non-smokers (right panel).
Figure 1

Number of female and male smokers (left and middle panels) and age distribution of smokers and non-smokers (right panel).

3.1 Surgery-related complications

Since the following complications are directly related to surgery, we defined them as surgery-related complications. The study registered 14 patients who experienced surgery-related complications (6.95%): 3 in the smoker group (6.12%) and 11 in the non-smoker group (8.03%). Of these, 12 had to undergo revision (4.87%). These complications included: one impression fracture of an L4 endplate in a 360° fusion of L3–L5; one iatrogenic fracture of an S1 pedicle; one excoriation due to the removal of surgical drapes; one extraforaminal hematoma with a persistent neurological deficit; three epidural hematomas (one patient was revised on day 2, one on day 4, and one on day 5); one patient with a screw malposition, who had to undergo revision; one patient with activated arthritis of the shoulder due to inappropriate positioning on the operating table; and one with a loosened screw (due to osteoporosis), which occurred 2 months postoperatively and needed revision. Furthermore, one patient had to undergo revision because of a weakness of dorsiflexion of the foot due to a bone fragment in the spinal canal. Another patient had to undergo revision because of a pedicle fracture that caused a space-occupying lesion in the spinal canal and one because of a dislocation of a TLIF. There were 3 patients (1 male and 2 females) in the smoker group and 11 patients (5 males and 6 females) in the non-smoker group, who suffered from surgery-related complications (Figure 2). This is consistent with the previously reported results, which indicate that the surgery-related complication rate was slightly lower in the smoker group. Nevertheless, we could not observe a statistically significant difference (p = 0.9).

Figure 2 
                  Number and percentage of smokers with and without perioperative complications.
Figure 2

Number and percentage of smokers with and without perioperative complications.

3.2 Smoking versus perioperative complications

We combined wound healing disorders (WHDs), hematomas, wound dehiscence, tension cavities, and incidental durotomies into perioperative complications. We encountered one patient (0.534%) with WHDs. Two patients (1.07%) developed a wound dehiscence, one of which needed a secondary suture, and nine patients had hematomas (4.81%). No patient in this group had to undergo a revision in the operating room. In 22 patients (11.64%), we recorded liquor leakages. We could not see a statistically significant difference between the smoker and the non-smoker groups (p = 0.46) for all four of these perioperative complications.

3.3 Smoking versus overall perioperative complication percentages (i.e., cerebrospinal fluid leakage, surgery-related complications, WHD, dehiscence, wound necrosis, hematoma, or tension cavity)

We coded this group as a binary variable. Adjusting for age to avoid the smoking-age-bias, considering only the group of patients not older than 64, and testing for equal overall perioperative complication rates in the smoker and the non-smoker groups (6 out of 45 smokers and 11 out of 40 non-smokers had at least one perioperative complication), we found no statistically significant difference (p = 0.17). We recognized DM, CHD, PAD, and cardiac disease as secondary diseases. Considering that secondary diseases might potentially lead to perioperative complications and considering the smoke-age-bias, we calculated two logistic regression models: (i) one with overall perioperative complication (yes = 1 and no = 0) as binary output and overall secondary disease (yes/no) as well as age and smoking (yes/no) as explanatory variables. Neither smoking (p = 0.080) nor overall secondary disease (p = 0.529) showed a statistically significant influence on the perioperative complication rate. (ii) Avoiding aggregation of secondary diseases, age, smoking, and each of the four aforementioned secondary diseases as separate explanatory variables in a multivariate logistic regression with perioperative complication (yes = 1 and no = 0) as binary output, we found a statistically significant influence of smoking (p = 0.049). However, we were not able to find any statistically significant impact of DM (p = 0.527), CHD (p = 0.349), PAD (p = 0.297), or cardiac diseases (p = 0.592) on the complication rate.

3.4 Smoking versus postoperative complications

We grouped any adverse event in the postoperative period under “postoperative complications.” In total, 18 possible postoperative complications were recorded for 186 patients; data were missing for 1 patient. Eighteen patients (9.68%) had a fever, whereas 45 (24.19%) had subfebrile temperatures. Seven patients (3.76%) had a urinary tract infection and two (1.08%) had pneumonia. One patient (0.54%) sustained fatal pulmonary emboli. Thirty patients (16.13%) had a neurological deficit, which included any form of self-reported transient sensation. Four patients had atrial fibrillation postoperatively (2.15%), two (1.08%) had cardiac ischemia, and one (0.54%) had a transient ischemic attack. Two patients had a myocardial infarction (1.08%), six had anemia (3.23%), and one patient each had enteritis, urinary retention, reflux esophagitis, (pre-)ileus, and an attack of gout (0.54%) (Table 1). Overall, postoperative complication percentages increase with age, implying that the smoking-age-bias might lead to lower percentages in the smoker group. The fact that overall postoperative disease percentages increase with age implies that the smoking-age-bias might lead to lower percentages in the smoker group. Only in pneumonia and subfebrile cases did the smoker group show (slightly) higher percentages. Nevertheless, we could not find any statistically significant differences between the smoker and the non-smoker groups for each postoperative complication. Testing for equal postoperative complication percentages in the smoker and the non-smoker groups, we could not find any statistical differences (p = 0.57).

Table 1

Number and percentage of postoperative complications in the smoker and the non-smoker groups

Complication Smoker No of patients Percentage
Anemia No 6 0.0438
Anemia Yes 0 0
Atrial fibrillation No 3 0.0219
Atrial fibrillation Yes 1 0.0204
Attack of gout No 1 0.0073
Attack of gout Yes 0 0
Cardiac ischemia No 2 0.0146
Cardiac ischemia Yes 0 0
Enteritis No 1 0.0073
Enteritis Yes 0 0
Ileus/preileus No 1 0.0073
Ileus/preileus Yes 0 0
Meningismus No 0 0
Meningismus Yes 0 0
Myocardial infarction No 2 0.0146
Myocardial infarction Yes 0 0
Neurological deficit No 24 0.1752
Neurological deficit Yes 6 0.1224
Pneumonia No 1 0.0073
Pneumonia Yes 1 0.0204
Pulmonary emboli No 1 0.0073
Pulmonary emboli Yes 0 0
Reflux oesophagitis No 1 0.0073
Reflux oesophagitis Yes 0 0
Respiratory tract infection No 0 0
Respiratory tract infection Yes 0 0
Subfebrile No 32 0.2336
Subfebrile Yes 13 0.2653
Temperature No 15 0.1095
Temperature Yes 3 0.0612
Transient ischemic attack No 1 0.0073
Transient ischemic attack Yes 0 0
Urinary retention No 1 0.0073
Urinary retention Yes 0 0
Urinary tract infection No 6 0.0438
Urinary tract infection Yes 1 0.0204

The probability of occurrence of at least one postoperative complication was not different between the smoker and the non-smoker groups (44.90 vs 48.18%, p = 0.7). Interestingly, we saw in the (smaller) male group a higher complication rate in the smoker group (61.11 vs 42.59%). In contrast, in the (larger) female group the complication was lower in the smoker group (35.48 vs 51.81%) (Figure 3). Although there is a stronger smoking-age-bias in the female group (approximately 3 years), this fact only partially explains the substantial difference. Adjusting for age to avoid the smoking-age-bias, considering only the group of patients not older than 64, and testing for equal overall complication rates in the smoker and the non-smoker groups (19 out of 45 smokers and 15 out of 40 non-smokers had at least one postoperative complication), we found no statistically significant difference (p = 0.82). Considering that secondary diseases might potentially lead to complications and considering the smoke-age-bias, we calculated two logistic regression models: (i) one with overall postoperative complication (yes = 1 and no = 0) as binary output and overall secondary disease (yes/no) as well as age and smoking (yes/no) as explanatory variables. Neither smoking (p = 0.642) nor overall secondary disease (p = 0.866) showed a statistically significant influence on the postoperative complication rate. (ii) Avoiding aggregation of secondary diseases, age, smoking, and each of the four aforementioned secondary diseases as separate explanatory variables in a multivariate logistic regression with postoperative complication (yes = 1 and no = 0) as binary output, we did not find any statistically significant influence of smoking (p = 0.114), DM (p = 0.858), CHC (p = 0.997), PAD (p = 0.074), or cardiac disease (p = 0.344).

Figure 3 
                  The postoperative complication rate in female and male smokers.
Figure 3

The postoperative complication rate in female and male smokers.

3.5 Smoking versus blood loss

We defined blood loss as the sum of blood loss during surgery, the monitoring phase, and the postoperative drainage phase. Mean blood loss during the surgery and monitoring phase was 93.54 (0–1,050 ml) in the entire sample, 79.38 ml (0–1,050 ml) in the smoking group, and 98.54 ml (0–1,000 ml) in the non-smoking group. Blood loss per drainage was 143.13 ml (0–790 ml) in the collective and 116.77 ml (0–410 ml) and 152.50 ml (0–790 ml) in the subgroups. Total blood loss was 237.18 ml (0–1,600 ml), 196.14 ml (0–1,150 ml), and 251.77 ml (0–1,600 ml). Age and blood loss (perioperative and monitoring) are weakly correlated (ρ ≐ 0.13, ρs ≐ 0.15) as are age and amount of drainage (ρ ≐ 0.18 and ρs ≐ 0.13). As a direct consequence of this fact, and given the smoking-age-bias, the smoker group shows a tendency toward less blood loss/drainage than the non-smoker group. Since testing for equal blood loss/drainage distributions and ignoring the smoking-age-bias might lead to wrong conclusions, we only focused on the descriptive statistics.

3.6 Smoking versus discharge day

Data for two patients were missing. The average length of stay (LOS) in hospital was 9.59 days (4–32 days), 9.02 days (5–24 days) in the smoker group, and 9.79 days (4–32 days) in the non-smoking group. For age and discharge day, Pearson correlation ρ and Spearman rank correlation ρs are given as ρ ≐ 0.1181 and ρs ≐ 0.1994. Testing for the null hypothesis of zero Pearson (Spearman) correlation yields a p-value of 0.1101 (0.006656). As a result of the age bias, we saw a tendency that the average LOS in the smoking patient cohort is shorter than that of the average non-smokers (Figure 4). Again, as ignoring the smoking-age-bias might lead to wrong conclusions, we focused on the descriptive statistics.

Figure 4 
                  Comparison of the discharge day in female and male smokers as well as non-smokers.
Figure 4

Comparison of the discharge day in female and male smokers as well as non-smokers.

4 Discussion

In this study, we investigated the perioperative complication rate in smokers undergoing minimally invasive fusion surgery. MIS techniques minimize soft tissue damage, reduce blood loss, show less postoperative pain, and a shorter hospital stay [11,12,13,14,15]. The impact of smoking on the general state of health is well known. Vogt et al. investigated the association between the smoking status of spinal surgery patients, the duration and severity of symptoms, and their self-reported health status. They found that smokers reported more severe symptoms than non-smokers [16]. Furthermore, those who were non-smokers reported better health status postoperatively than those who smoked. Smoking increases the risk of pseudarthrosis in both lumbar and cervical fusion procedures [1,2,3,4,5]. In this study, we focused on the perioperative effects of smoking tobacco in MIS fusion procedures of the spine. Turan et al. evaluated more than 5,00,000 patients to determine the effect of smoking on 30-day perioperative outcomes in noncardiac surgical patients [17]. In their study, current smokers were 1.38 times more likely to die than patients who had never smoked. They also had significantly greater odds of suffering from pneumonia, requiring unplanned intubation or needing mechanical ventilation. Current smokers were substantially more likely to experience a cardiac arrest, myocardial infarction, and stroke. Seicean et al. saw similar effects of smoking on the perioperative outcome of patients undergoing elective surgery [18]. They selected 14,500 patients who needed elective spinal surgery from the American College of Surgeons National Surgical Quality Improvement database and divided them into current, prior, and never smokers. Compared with both prior and never smokers, current smokers had fewer comorbidities, abnormal laboratory values, and intra/postoperative transfusions. Previous smokers were older than current and never smokers, had more comorbidities and abnormal lab values, and were less likely to be operated on by the attending surgeon alone. Prior smokers were also found to have a significantly greater number of major complications than never smokers, with 7 and 5.4% being affected, respectively. Current smokers with more than 60 pack-years were more likely than never smokers to die within 30 days of surgery. However, smoking itself was not found to be associated with poorer operative or 30-day outcomes in nearly all patients undergoing elective spinal surgery. De la Garza Ramos et al. investigated 1,368 patients who underwent surgery for adult spinal deformity and saw no significant difference between smokers and non-smokers when it came to the development of complications, either in major complication rates or increased odds of developing any complication or major complication [19]. In our group, we could not detect any significant difference between smokers and non-smokers when it came to surgery-related complications in our cohort. We could not identify any statistically significant differences between peri- or postoperative complications and smoking. In the overall perioperative complications group, we found a weak, statistically significant smoking influence (p = 0.049). Possible relevant secondary diseases such as DM, CHD, PAD, or cardiac diseases did not influence the results.

Due to the significantly lower average age of smokers in the sample and the fact that age has a weak positive correlation with peri- and postoperative complication rates, the corresponding complication rates were slightly lower in the smoker group. There was only a marginally greater number of patients suffering from subfebrile temperatures or pneumonia in the smoker group. Interestingly, we saw a higher rate of postoperative complications in the male smoker group (61.11 vs 42.59%), whereas in the larger female group, the rate of postoperative complications was lower in the smoker group (35.48 vs 51.81%). Tobacco smoking increases the risk of wound complications and infection by reducing tissue oxygenation and blood flow. Smoking also decreases the effectiveness of inflammatory cell function and oxidative bactericidal mechanisms. Furthermore, reparative cell functions are inhibited [20]. Nevertheless, the literature provides diverging positions concerning smoking and wound infection. Turan et al. found that current smokers had significantly higher odds of having superficial and deep incisional infections, sepsis, organ space infections, and septic shock [17]. Veeravagu et al., who studied 24,774 patients, reported that smokers had a statistically significant higher rate of infection than non-smokers (OR: 1.19, 95% CI: 1.02–1.37) [21]. On the other hand, Cizik et al., who worked with 1,532 patients, found that smoking was not a significantly contributing factor in surgical site infections (SSIs) [22]. Lee et al. developed a predictive model for the occurrence of SSI after spinal surgery [23]. Interestingly, a history of congenital heart failure was the greatest medical risk factor for SSI in multivariate analysis. The odds of SSI in these patients were 3.07 times higher than they were for those without congenital heart failure when adjusted for surgical invasiveness and diabetes. According to their analysis, a 65-year-old man with a history of rheumatoid arthritis and diabetes, undergoing an L4–L5 laminectomy and transforaminal interbody fusion, has an 11.84% chance of SSI requiring an operative debridement. Smoking was considered as a predictor variable but was not defined as a criterion for infections. Ee et al. investigated the medical records of 2,299 patients after TLIF procedures, laminectomies, or discectomies comparing MIS with open spinal surgery [24]. Patients undergoing open spinal surgery were 5.77 times more likely to suffer from an SSI than MIS approaches. Furthermore, diabetes, the number of levels operated on, and body mass index were predictive of an increased SSI risk. Smoking was not a risk factor for suffering from an SSI. We observed no severe WHDs in our patients. We noted one WHD (0.534%) due to dry necrosis of the wound margin, one case of wound dehiscence that needed a secondary suture, and four superficial WHDs in the form of tension cavities (2.139%). We observed no significant difference between the smoking and non-smoking groups, but we did observe slightly better results in the smoking group. Smoking is associated with longer hospital stays. In their survey of 160 patients who underwent anterior cervical corpectomy, Lau et al. found that current smokers were subject to higher complication rates (p < 0.001) and longer lengths of stay (p < 0.001) [1]. Seicean et al. divided their cohort of 14,500 adults into current, prior, and never smokers [18]. Mean LOS was 2 days for all three groups. Current smokers had a shorter interquartile range of 1–3 days, compared with 1–4 days for both prior and never smokers. Interestingly, former smokers were most likely to have prolonged LOS (30.2%), whereas current smokers were the least likely (22.2%). Patients smoking more than 60 pack-years had a higher likelihood of a prolonged LOS than never smokers. In our study group, the mean LOS was around 9 days in both the smoking and the non-smoking groups. We saw that the average smoker in our patient cohort had spent less time in hospital than the average non-smoker. Very little research has been carried out in a possible association between smoking and intraoperative blood loss and perioperative transfusion use in patients undergoing spinal surgery. McCunniff et al. investigated 581 lumbar decompression cases with or without fusion [25]. They found that smokers had an increased estimated blood loss compared with non-smokers (mean 328 ml more for each pack smoked per day; 95% CI: 249–407 ml; p < 0.001). They also found that smokers had a greater perioperative transfusion rate than non-smokers. In our cohort, the average smoker suffered less blood loss/drainage than the average non-smoker. To our knowledge, this is one of the largest single-center studies investigating MIS procedures. A limitation of this study might be the close relationship of young age and smokers. Nevertheless, because of this very relationship, it would be even more remarkable if more adverse events were observed in the smoking group. This aspect in particular was not observed among our cohort.

5 Conclusion

The negative impact of smoking on health is undeniable. In the EU, one person out of four is a smoker (Eurostat). Consequently, spine surgeons must treat a significant population of patients who smoke. In our cohort of 187 patients undergoing surgery in a single center, smokers did not show an elevated risk of perioperative complications in MIS fusion. The use of MIS fusion techniques does itself provide a low comorbidity, too [15]. We do, of course, recommend postoperative smoking cessation, since this helps to reverse the impact of cigarette smoking on outcomes following spinal fusion, particularly as regard to a lower nonunion rate or a higher return to work rate [4].

  1. Conflict of interest: The authors state no conflict of interest.

  2. Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Received: 2020-05-31
Revised: 2020-11-10
Accepted: 2020-12-05
Published Online: 2021-01-27

© 2021 Wolfgang Senker et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  5. Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
  6. Research Articles
  7. GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway
  8. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  9. Additional baricitinib loading dose improves clinical outcome in COVID-19
  10. The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
  11. SLC12A8 plays a key role in bladder cancer progression and EMT
  12. LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
  13. Case Report
  14. Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
  15. Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
  16. Research Articles
  17. TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
  18. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
  19. LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
  20. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
  21. Rapid Communication
  22. COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
  23. Case Report
  24. Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
  25. An infertile female delivered a baby after removal of primary renal carcinoid tumor
  26. Research Articles
  27. Hypertension, BMI, and cardiovascular and cerebrovascular diseases
  28. Case Report
  29. Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
  30. Research Articles
  31. Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
  32. Review Articles
  33. Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
  34. Research Articles
  35. Thermography in the diagnosis of carpal tunnel syndrome
  36. Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
  37. Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
  38. The influence of smoking in minimally invasive spinal fusion surgery
  39. Impact of body mass index on left atrial dimension in HOCM patients
  40. Expression and clinical significance of CMTM1 in hepatocellular carcinoma
  41. miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
  42. Comparison of multiple flatfoot indicators in 5–8-year-old children
  43. Early MRI imaging and follow-up study in cerebral amyloid angiopathy
  44. Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
  45. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
  46. Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
  47. Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
  48. Review Articles
  49. The ambiguous role of mannose-binding lectin (MBL) in human immunity
  50. Case Report
  51. Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
  52. Fertility problems in males carrying an inversion of chromosome 10
  53. Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
  54. Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
  55. Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
  56. Skull hemophilia pseudotumor: A case report
  57. Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
  58. Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
  59. Clinicopathologic features of Good’s syndrome: Two cases and literature review
  60. Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
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