Case report: Regression after low-dose glucocorticoid therapy in a case of acute immune myocarditis induced by anti-PD-1 therapy for NSCLC.

Background: PD-1 inhibitors exhibit efficacy in managing unresectable/metastatic driver gene-negative NSCLC, albeit with potential immune-related adverse events (irAEs). Among these, immune checkpoint inhibitor-associated myocarditis (ICI-M) is rare yet lethal. This study presents the initial successful instance of ICI-M in a lung cancer patient, rescued by low-dose glucocorticoids post-deterioration during treatment. Case summary: A 78-year-old male with a medical history of stage IV pT3N2M1 NSCLC underwent four cycles of palliative chemotherapy, resulting in stable disease (SD). Subsequent to declining further chemotherapy, the patient was transitioned to a targeted therapy regimen comprising Anlotinib in conjunction with PD-1 inhibitor immunotherapy. On the 26th day post-administration of the PD-1 inhibitor, the patient manifested Grade 2 immune-mediated myocarditis. Treatment encompassing 1mg/kg methylprednisolone combined with immunoglobulin shock therapy was initiated for 3 days, achieving symptomatic control. Nonetheless, upon tapering methylprednisolone dosage to 4-8mg/3-4d, the condition deteriorated, necessitating transfer to the intensive care unit. Methylprednisolone dosage was escalated to 80mg/day for 3 days, followed by gradual reduction by one-third to two-thirds weekly, culminating in the patient's safe discharge from the hospital. Conclusion: Immune-related myocarditis linked to checkpoint inhibitors is often managed effectively with high-dose glucocorticoid therapy. However, in Asian populations, low-dose glucocorticoids are increasingly utilized for salvage therapy, yielding favorable outcomes and improving prognosis compared to European populations.

Forkhead Box S1 mediates epithelial-mesenchymal transition through the Wnt/ß-catenin signaling pathway to regulate colorectal cancer progression.

BACKGROUND: Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. METHOD: FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/ß-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. RESULT: Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P < 0.05). Upregulation of FOXS1 association with poor prognosis of CRC patients. si-FOXS1 induced apoptosis and inhibited proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT), and the Wnt/ß-catenin signaling pathway in vitro; sh-FOXS1 inhibited the volume and weight of subcutaneous xenografts and the number of lung metastases in vivo. LiCl, an activator of Wnt signaling, partially reversed the effect of FOXS1 overexpression on CRC cells. CONCLUSION: FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/ßcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.

Case Report: Radiotherapy Plus Immunotherapy and Lenvatinib for the Treatment of Recurrent Hepatocellular Carcinoma With a Right Atrium and Inferior Vena Cava Tumor Thrombus.

Background: The treatment of hepatocellular carcinoma (HCC) with right atrium (RA) and inferior vena cava (IVC) tumor thrombi is challenging, with the standard treatment being not well established. Immunotherapy plus antiangiogenic therapy is a potentially effective treatment for patients with advanced HCC. Here, we described the case of a patient with HCC with RA and IVC tumor thrombi who achieved a successful response from radiotherapy and targeted therapy plus immunotherapy. Case Summary: A 62-year-old women presented with severe bilateral lower extremity edema identified as recurrent HCC with RA and IVC tumor thrombi based on past medical history and computed tomography. The patient received palliative radiotherapy plus pembrolizumab and lenvatinib treatment and was relieved of disease symptoms of bilateral lower extremity edema. The HCC with RA and IVC tumor thrombi shrunk, and the progression-free survival of this patient was > seven months. Conclusion: Tumor thrombus-directed radiotherapy plus concurrent immunotherapy and targeted therapy might be a feasible and safe approach for patients with HCC with RA and IVC tumor thrombi.

Short-term posterior C1-C2 pedicle screw fixation without fusion to treat type II odontoid fracture among people under 60 years.

INTRODUCTION: Posterior C1-C2 pedicle screw fixation is a reliable technique used in treatment of type II odontoid fracture. However, the loss of cervical range of rotation motion (RORM) was inevitable. There were few studies focusing on the influence of short-term C1-C2 fixation with nonfusion technique to preserve cervical function in patients younger than 60 years. The purpose of this study was to compare cervical RORM which was measured by an improved goniometer, and the clinical outcomes between short-term and long-term C1-C2 fixation techniques in the treatment of Grauer type 2B and 2C odontoid fracture. MATERIALS AND METHODS: This study represents a retrospective analysis, including patients who underwent primary C1-C2 fixation surgery. These patients were divided into short-term and long-term groups based on whether underwent a fixation removal operation. The clinical results were collected and compared between the two groups. Independent T test and Chi-square analyses were used to identify significant differences between the two groups and dependent T test was used within each group. Statistical significance was set at p < .05. RESULTS: There were no severe postoperative complications, and all 60 patients achieved spinal stabilization after primary surgery. The mean rotation angle in the short-term group at last follow-up time was 138.39 ± 21.06°, which was better than 83.59 ± 13.06° in the long-term group (p < .05). The same statistical difference was observed in flexion-extension angle, which was 71.11 ± 18.73° in short-term group and 53.34 ± 18.23° in long-term group. The mean NDI score in short-term group at last follow-up time was 1.23 ± 0.86 and better than 8.24 ± 3.17 in long-term group. However, the VAS score in short-term group was 1.82 ± 0.54 which was worse compared to 0.64 ± 0.29 in long-term group. CONCLUSIONS: The results demonstrated that primary C1-C2 fixation with nonfusion technique could support satisfactory clinical effects. In addition, the removal of instruments after bony fusion could improve the function of cervical movement significantly in patients under 60 years.

The retropharyngeal steroid use during operation on the fusion rate and dysphagia after ACDF? A systematic review and meta-analysis.

PURPOSE: The aim of this meta-analysis was to investigate the effects of retropharyngeal steroid use during operation on bony fusion and dysphagia rate after ACDF. METHODS: We searched the electronic literature database of PubMed, Embase and the Cochrane Library published from January 1990 to February 2020. The size of each group, mean age, proportion of female patients, dysphagia events and fusion rate at one-year follow-up were extracted. RevMan 5.3 was used for the meta-analysis. RESULTS: A total of eight studies including six RCTs and two case-control studies met the inclusion criteria. This meta-analysis showed that retropharyngeal steroids could achieve significantly lower dysphagia rates (p < 0.001), higher fusion rates (p = 0.01), less moderate and severe events rates according to the Bazaz stratification (p < 0.001). However, there was no significant difference between two groups regarding operation time (p = 0.67), blood loss (p = 0.33), VAS scores at one day (p = 0.90) and VAS scores at two weeks (p = 0.80). CONCLUSIONS: Retropharyngeal steroid use is an effective method in reducing dysphagia rate, severe dysphagia rate and increasing fusion rate during ACDF surgery, without increasing operating time, blood loss or VAS scores at one day and two weeks. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Occipitocervical Revision Surgery Using the Bicortical Screw and Plate System for Failed Craniovertebral Junction Stabilization.

BACKGROUND: To evaluate the clinical efficacy and safety of the modified technique utilizing the occipital bicortical screws and plate system in occipitocervical revision surgery. METHODS: Between October 2010 and May 2018, 12 consecutive patients were retrospectively evaluated. All patients had posterior occipitocervical resurgery utilizing modified technique of bicortical screws and occipital plate. The measurements of extracranial occiput on midline were conducted on computed tomography (CT) scans. The thickness of the occipital bone at the location of external occipital protuberance and below 15 mm were evaluated, respectively. For the procedure, the trajectory was drilled perpendicular to the external occipital protuberance for the specified depth with a depth-limited drilling, 2 mm away from the internal bone plate, then the trajectory was deepened at intervals of 1 mm each time until reaching the internal bone plate. Meanwhile, a probe was used to explore all the walls of the trajectory. Bicortical screws were inserted to the occipital plate and the depth of penetration was less than 2 mm from the internal bone plate. Clinical efficacy and radiographic evaluation were followed up. RESULTS: The thickest point was the external occipital protuberance, which was 15.49 ± 1.47 mm and decreased gradually on the midline to 13.41 ± 1.60 mm at below 15 mm. Twelve cases (mean age 41.17 years; range, 24-62 years), including five males and seven females, were followed up for 24.08 months (14-32 months). The interval time was 40.42 months (3-156 months) after the initial operation. At the final follow-up, JOA score increased from 8.58 ± 2.53 before surgery to 12.67 ± 1.84 (P < 0.05) and VAS score improved from 6.17 ± 1.21 to 2.08 ± 1.32 (P < 0.05). Besides, clinical symptoms were relieved in all patients after revision surgery. All patients had rigid internal fixations with bone fusion and no major complications occurred. CONCLUSIONS: Posterior occipitocervical plate-screw system with bicortical screws had the advantages of safety, simple and promising efficacy without excessive tissue release or intraspinal manipulation, proving that it's valuable as a modified technique for occipitocervical revision surgery.

The ratio of the posterior atlanto-occipital interval (PAOI): a novel radiographic ratio method evaluating the risk of cervical spondylotic myelopathy-a case-control study.

BACKGROUND: Our study aims to introduce a dynamic interval ratio method calculated using cervical hyperextension-flexion X-ray films. Secondarily, we aim to evaluate the relationship between the posterior atlanto-occipital interval ratio and cervical spondylotic myelopathy and explain the rationale. METHODS: We reviewed 83 cases with visible cervical dynamic X-ray films in our hospital from February 2015 to December 2018. Cases were divided into 2 groups according to their diagnosis (with or without spondylotic myelopathy). Radiographic measurements included the shortest distance between the posterior arch of the atlas and the occipital bone and cervical range of motion, and demographic data such as gender, age, and body mass index were also extracted. The posterior atlanto-occipital interval ratio (distance at hyperextension position/distance at hyperflexion position) was determined using logistic regression analysis models between the 2 groups. RESULTS: We included 40 cases in the disease group and 43 cases in the control group. The mean posterior atlanto-occipital interval ratio was 0.65±0.30 (mean ± standard deviation) in the disease group and 0.30±0.28 in the control group, with a significant difference (P<0.01). There was no correlation between the posterior atlanto-occipital interval ratio and gender or body mass index. However, the interval ratio had strong correlations with age, cervical spondylotic myelopathy, and Japanese Orthopaedic Association scores. Age, posterior atlanto-occipital interval ratio, and interval distance at hyperextension in the disease group were higher than those of the control group. Contrastingly, range of motion, Japanese Orthopaedic Association scores, and interval distance at the disease group's hyperflexion position were lower than in the control group. In all cases, the risk of cervical spondylotic myelopathy in the T2 group (cases with middle posterior atlanto-occipital interval ratio, according to the tertiles) was 6 times more than the T1 group (cases with lower ratio), and the T3 group (cases with higher ratio) had a 26.4 times greater risk than the T1 group. CONCLUSIONS: Our results suggest that the posterior atlanto-occipital interval ratio is a simple and meaningful parameter that could provide prognostic value for the risk of cervical spondylotic myelopathy through the imaging examinations of the selected cases. Higher posterior atlanto-occipital interval ratios indicate a greater risk for cervical spondylotic myelopathy and cervical musculoskeletal dysfunction. A higher posterior atlanto-occipital interval ratio may manifest undetected posterior atlanto-occipital stiffness, which needs more pathological evidence in future studies.

Personality Traits Affect the Cost-Effectiveness of Total Knee Arthroplasty.

OBJECTIVE: To assess the clinical benefit and compare the cost-effectiveness of total knee arthroplasty (TKA) in patients with different personality traits. METHODS: The present study was retrospectively conducted from January 2017 to May 2018. A total of 232 patients between 46 and 71 years old who underwent unilateral, primary TKA with the diagnosis of knee osteoarthritis were interviewed. Three types of data were required to compare the cost-effectiveness differences among groups: personality traits, postoperative clinical outcomes about health-related quality of life, and costs associated with TKA. Personality was assessed using the Eysenck Personality Questionnaire, functional outcome was assessed through the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, and costs were evaluated. Besides, the marginal cost-effectiveness ratio (MCER) as the primary outcome, which relates the direct costs to the associated patient benefit as assessed by the clinical endpoint ($/quality-adjusted life years [QALY]), was compared among different personality traits. All information for this study was acquired by directly interviewing the patients and reviewing the medical computer records at our hospital. RESULTS: Two hundred and eleven patients completed the final analysis with an average of 24.6 months follow-up postoperatively. The choleric group, sanguine group, melancholic group, and phlegmatic group has 41, 70, 46, and 54 patients, respectively. A statistically significant difference in MECR, QALYs, and postoperative WOMAC existed among different personality traits (all P < 0.05). There was no significant difference in mean age (P = 0.588), body mass index (BMI) (P = 0.790), smoking (P = 0.934), heavy drinking (P = 0.994), chronic comorbidities (all P > 0.05), preoperative albumin <3.5 g/dL (P = 0.991), and American Society of Anaesthesiologists (ASA) score (P = 0.687) among personality traits. More women tend to be melancholic in comparison to other personality traits (P = 0.016). Melancholic patients attested inferiority of TKA compared with other personality traits, who would pay for the same QALYs at the highest costs (P < 0.05). By contrast, sanguine patients have a more cost-effective TKA than other personality traits, as they pay the least money for the same QALYs (P < 0.05). Although phlegmatic and choleric patients seemingly have moderate gains from TKA, in general, the extroversion (measured by the extroversion subscale) and stability (measured by the neuroticism subscale) displayed more pleasurable QALYs in comparison with introversion and instability (P < 0.05). Sensitivity analysis showed that the results mentioned above appeared not to be sensitive when varying key parameters (prosthesis survival and life expectancy) in a one-way sensitivity analysis. Sanguine and melancholic patients still have the lowest and highest MCER in comparison with choleric and phlegmatic traits (P < 0.05). The multivariate logistic regression showed that RA (adjusted OR = 1.3, 95% CI = 1.2-1.4, P < 0.01), ASA Class I-II (adjusted OR = 0.9, 95% CI = 0.8-1.0, P < 0.001), sanguine (adjusted OR = 0.8, 95% CI = 0.7-0.9, P < 0.001) and melancholic (adjusted OR = 1.2, 95% CI = 1.1-1.3, P < 0.001) were significantly associated with MCER. CONCLUSIONS: Before surgery, screening the melancholic patients would significantly reduce the economic burden, avoid unnecessary suffering, and shorten the recovery period.

Flexion Dysfunction of Atlanto-Occipital Joint Associated with Cervical Spondylosis.

OBJECTIVE: To investigate the association between atlanto-occipital radiographic alignment in flexion and cervical spondylosis (CS). METHODS: This is a retrospective case-control study. CS patients were recruited from our hospital, and the age/gender/body mass index (BMI)-matched healthy controls were selected from the subjects in health examinations at the same hospital between January 2015 and May 2019. A total of 464 subjects was included in the study. There are 282 males and 182 females. The ages of patients were 20 to 67 years, and the mean age was 33.9 years. CS patients were considered the case group. Based on surgical treatments, they were subdivided into non-operation group and operation group. The operation group and non-operation group had 45 and 187 patients, respectively, while 232 subjects were included in the control group. The angle between McGregor's line and C1 line (O-C1 angle) was evaluated on images taken in flexion (F-OC) and neutral positions (N-OC) independently. The relationship between the FOC (FOC=F-OC-N-OC) and Neck Disability Index (NDI) was examined, and the involvement of the FOC in the onset of CS was analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off for detecting an increased risk of CS. RESULTS: The median follow-up time was 51.6 months (25-115 months). The case groups, especially the operation group, tended to be older (55.8 ± 11.2 vs 41.6 ± 13.8 vs 23.5 ± 5.5 years, P < 0.001), have a higher NDI score (12.2 ± 4.5 vs 6.2 ± 2.1 vs 3.2 ± 1.2, P < 0.001), and longer medical history (10.5 ± 9.5 vs 6.8 ± 11.2 years, P < 0.001). One-way analysis of variance showed statistically significant differences in FOC between the control and case groups (1.4° ± 1.2° vs 3.6° ± 1.9° vs 7.2° ± 2.0°, P < 0.001). Besides, a post-hoc Tukey test showed a lower FOC in the operation group compared with that in the non-operation group (1.4° ± 1.2° vs 3.6° ± 1.9°, P < 0.001). Using FOC as a radiological predictive model to predict CS, the cut-off value was 4.2°. Using FOC as a radiological predictive model to predict CS, the area under the curve (AUC) was 0.86 (95% CI: 0.78-0.92, P < 0.001). In the univariable risk analysis model, conditional logistic regression showed that the FOC level was an independent factor with an important role in the risk of CS. The odds rose to 8.2 times when FOC reached the level under 4.2° (OR = 8.2; 95% CI: 6.4-10.0; P < 0.001). There existed a significant negative correlation between FOC levels and NDI (r = -0.451, P = 0.016). CONCLUSIONS: Stiff O-C1 , which is defined as FOC ≤ 4.2°, represented decreased flexion dysfunction of atlanto-occipital joint and is closely associated with high risk for the occurrence of CS. This finding could show a possible relationship between upper and lower cervical spine and help spine surgeons to understand the pathological process of CS and implement appropriate management.

Late-onset anastomotic leak following sweet esophagectomy: A case report and review of the literature.

RATIONALE: Late-onset anastomotic leak (AL) is an uncommon but potentially lethal complication after esophagectomy. PATIENT CONCERNS: A 74-year-old male patient was readmitted due to chest distress and chills about 3 months after initial esophagectomy for cancer. DIAGNOSES: The previous endoscopic biopsy revealed primary esophageal squamous cell carcinoma, and sweet esophagectomy with gastric conduit reconstruction was therefore performed. The patient developed AL 3 months after the surgery. INTERVENTIONS: Naso-leakage extraluminal drainage tube was utilized because the symptoms of the patient were aggravated 1 month after the chest tube drainage since his second admission for AL. OUTCOMES: Twenty-one days after naso-leakage extraluminal drainage, the computed tomography images showed the healing of the leakage. Then the patient was discharged from the hospital. LESSONS: Late-onset AL should be kept in mind when the patient complained of chest distress and fever during the follow up after esophagectomy. In addition, naso-leakage extraluminal drainage could be considered for the treatment of AL. Further trials for better evidence are warranted.

Raloxifene Prevents Early Periprosthetic Bone Loss for Postmenopausal Women after Uncemented Total Hip Arthroplasty: A Randomized Placebo-Controlled Clinical Trial.

OBJECTIVE: To examine the results of raloxifene for prevention of periprosthetic bone loss around the femoral stem in patients undergoing total hip arthroplasty (THA). METHODS: Between January 2015 and May 2017, 240 female patients between 55 and 80 years underwent primary THA and were randomly allocated to receive 60 mg raloxifene hydrochloride per day (treatment group, TG, n = 120) or placebo (control group, CG, n = 120) orally at bedtime using computer-generated randomization sequence generation. Baseline data, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), women's quality of life (QoL) score, bone mineral density (BMD) around the prosthesis, and adverse events were compared between the two groups. The measuring range of BMD around the prosthesis was divided into seven regions of interest (ROI). The sample size was calculated to detect a mean difference in BMD of 0.15 g/cm2 with a standard deviation (SD) of 0.3. The error was set at 0.05 and the power level at 90% with additional compensation for a possible dropout rate of 20%. RESULTS: A total of 240 participants in the study up to 24 months after THA. There were no significant differences in the mean BMD of all the zones between groups before surgery (all P > 0.05). However, there were significant differences in the BMD of Gruen zones 4 and 7 between groups at 6 months postoperatively (both P < 0.05); there were significant differences in Gruen zones 1, 4, 6, and 7 at 12 months postoperatively (all P < 0.01); there were significant differences in Gruen zones 1, 2, 4, 6, and 7 at 24 months postoperatively (all P < 0.001). Patients taking raloxifene reported higher QoL scores, with better improvement in BMD in all areas except in zones 3 and 5 compared with the control group. There were no significant differences in WOMAC pain (P = 0.4045), WOMAC function (P = 0.4456) and women's QoL scores (P = 0.5983) between groups before surgery. However, WOMAC pain, WOMAC function and women's QoL score in the treatment group were significantly better at all time points (all P < 0.05). Patients in the treatment group showed no increased adverse events, including cardiac events, stroke, venous thromboembolism, and gynecological cancer (all P > 0.05), but did show decreased odds of breast cancer in comparison with those using a placebo (P = 0.0437). CONCLUSION: Raloxifene can help inhibit bone loss around the prosthesis and improve the QoL of postmenopausal women after THA with no increased adverse events, and can even decrease the odds of breast cancer.

Lobaplatin induces pyroptosis through regulating cIAP1/2, Ripoptosome and ROS in nasopharyngeal carcinoma.

Cisplatin is the most commonly used chemotherapeutic drug for nasopharyngeal carcinoma (NPC), while its side effects are often intolerable. Lobaplatin, as an effective third-generation platinum with fewer adverse reactions and less platinum cross-resistance, has been considered as a good alternative to cisplatin after cisplatin's failure (relapse or metastasis) in the treatment of NPC. However, the anti-NPC mechanism of lobaplatin remains largely unknown. In present study, 50% inhibiting concentration (IC50) of lobaplatin for NPC cells is found to be similar to that of cisplatin. 10 µM and 20 µM lobaplatin caused obvious gasdermin-E (GSDME)-mediated pyroptosis by activating caspase-3. Moreover, we found lobaplatin induced proteasomal degradation of cell inhibitor of apoptosis protein-1/2 (cIAP1/2). And these pyroptotic phenomena could be suppressed by the recovery of cIAP1/2, suggesting that cIAP1/2 are critical in lobaplatin-induced pyroptosis. Further inhibition of cIAP1/2 by birinapant (an antagonist of cIAP1/2) dramatically enhanced pyroptosis induced by lobaplatin in vitro and in vivo, which was consistent with the combination with cisplatin. Importantly, this synergistic pyroptotic effect were suppressed by the inhibition of Ripoptosome (RIPK1/Caspase-8/FADD), reactive oxygen species (ROS) and caspase-3 cleavage, and were independent of phosphorylation of JNK and NF-κB signal. Our data reveal that cIAP1/2 play important roles in lobaplatin-induced NPC cell pyroptosis, and this anti-NPC effect can be significantly potentiated by cIAP1/2 antagonist birinapant through regulating the formation of Ripoptosome and the generation of ROS. These study provides a possibility to further reduce the platinum-related adverse events and chemoresistance of lobaplatin while maintaining satisfactory anti-NPC efficacy.

S-1 plus apatinib followed by salvage esophagectomy for irinotecan-refractory small cell carcinoma of the esophagus: A case report and review of the literature.

RATIONALE: Small cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before. PATIENT CONCERNS: A 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams including abdomen computed tomography excluded distant metastasis. DIAGNOSES: Primary SCCE (pT1bN1M0, IIB) was established after salvage operation. INTERVENTIONS: The tumor was enlarged after 1 cycle of first-line chemotherapy using irinotecan plus cisplatin, which indicated drug resistance. Second-line oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval) for a month showed efficacy, as shown by decreased serum neuron-specific enolase and stable of the esophageal lesion. Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months. In addition, maintenance therapy using low-dose apatinib (250 mg daily) plus S-1 (40 mg, twice daily for 4 weeks with a 2-week interval) were administered for another 6 months. Then the patient was followed up irregularly at the outpatient clinic. OUTCOMES: The adverse events including hand-foot syndrome, hypertension, vomiting, leukopenia, impaired hepatic function, and fatigue were mainly tolerable. Forty months after the operation, he was readmitted for back pain and disseminated bone metastases appeared in magnetic resonance images. His progression-free survival could not be obtained precisely, and his overall survival was longer than 40 months up to September 2019. LESSONS: S-1 plus apatinib followed by a timely esophagectomy with curative intent might be an alternative option for chemotherapy-refractory SCCE in selected patients. Better evidence is warranted.

Topological phase transition and tunable electronic properties of hydrogenated bismuthene: from single-layer to double-layer.

Planar bismuthene grown on SiC substrate provides a promising candidate to engineer van der Waals double-layer (DL) made of two dimensional (2D) topological insulators. We perform systematical calculations in DL hydrogenated bismuthene (H-Bi) that can be used to simulate the experimentally grown planar bismuthene to explore realizable 2D topological insulator van der Waals DL. Two possible geometry configurations of AA- and AB-stacked DL H-Bi are investigated. Due to pseudo Jahn-Teller effect, AB-stacked DL H-Bi has a strong interlayer coupling interaction and shows buckled lattice. Particularly, both AA- and AB-stacked DL H-Bi are topologically trivial rather than topologically nontrivial. The physical origin of the trivial topology is clarified by analyzing orbital composition. We discuss how the electronic properties are modified by interlayer coupling, external strain, and metal atom intercalation. It is also found that, for AB-stacked DL H-Bi, metal atom intercalation gives rise to novel multiple Rashba splitting near the valence band top, which is expected to manipulate the same spin in different planar bismuthene layers. Our results present various and tunable electronic properties of van der Waals DL H-Bi and allow for probing into multiple Rashba effect in 2D inversion-asymmetric topological insulators.

[Correlation of the grades of histologic prostatic inflammation with the risk of prostate cancer in biopsy specimens from men with total PSA of 4－10 µg/L].

OBJECTIVE: To investigate the association of the grades of histologic prostatic inflammation (HPI) with prostate cancer in biopsy specimens for male patients with total serum PSA (tPSA) of 4－10 µg/L. METHODS: We performed prostate biopsy for 200 patients with tPSA of 4－10 µg/L from January 2015 to December 2017. We determined the location, extent and intensity of HPI and analyzed the correlation of the grades of HPI with the risk of prostate cancer. RESULTS: Of the 200 biopsy specimens, BPH was detected in 169 (84.5%) and PCa in 31 (15.5%). Statistically significant differences were found in the positive rates of PCa between grades 1, 2 and 3 HPI, which were 19.3%, 25.8% and 54.8% based on the location (P < 0.01), 77.4%, 19.4% and 3.2% based on the extent (P < 0.01), and 51.6%, 29.0% and 19.4% based on the intensity of the lesion (P < 0.01), but not in the positive rates of BPH (P > 0.05). Multivariate logistic regression analysis showed that the risk of PCa was correlated negatively with the location (95% CI: 0.052－0.407, OR = 0.113, P = 0.001, r = －2.078) and extent of HPI (95% CI: 0.068－0.819, OR = 0.231, P = 0.023, r = －1.526) but not correlated with its intensity (95% CI: 0.796－4.193, OR = 1.804, P = 0.215). The positive predictive value, negative predictive value, sensitivity and specificity of the combined application of the location and extent of HPI in differentiating PCa from BPH were 51.2%, 90.3%, 91.5% and 50.8%, respectively. CONCLUSIONS: The location and extent of HPI are negatively while its intensity is not correlated with the risk of PCa. The grading of HPI based on its location and extent could help reduce the repetition of prostate biopsy.

Value of evaluating procalcitonin kinetics in diagnosis of infections in patients undergoing laparoscopic radical cystectomy.

Postsurgery infection is a common complication after laparoscopic radical cystectomy (LRC) followed by urinary diversion. White blood cell (WBC) values and C-reactive protein (CRP) are routinely used as markers for infection, but lack of specificity and their elevation is often delayed in clinically significant events. In this study, we aimed to investigate the value of procalcitonin (PCT) kinetics in assisting early diagnosis of infection in patients undergoing LRC.The patients' medical records between May 2013 and May 2016 were reviewed retrospectively. WBC, CRP, and PCT plasma levels as well as clinical symptoms were registered in 306 patients preoperatively (day 0), and 5 consecutive days postoperatively. Based on microbiological and clinical data, patients were grouped into noninfection- (NI-) and infection- (I-) groups. The day of new onset infection was observed were defined as day t0 and the day after that as day t1. For the NI-group, the day on which PCT was at the peak was defined as day t1 and the previous day as day t0.Of the 306 patients, 46 (15.03%) have proven infection. PCT levels were analogous at day t0:NI-group [median (interquartile range)]: 0.69(1.99) vs I-group [median (interquartile range)]: 1.0[0.75], P = .1. PCT levels were significantly increased at day t1 in the I-group[median (interquartile range)]:2.9(1.3) vs NI-group[median (interquartile range)]: 1.3(1.5), P < .01. The area under the curve for the prediction of infection was 0.72 [95% confidence interval (CI) = 0.63-0.81] for the absolute value of PCT; and for delta PCT:0.88 (95% CI = 0.81-0.94), P < .01. The optimal cut-off value was 0.79 ng/mL with the highest Youden index of 0.80 for delta-PCT to indicate infection. Neither absolute values nor changes in CRP, or WBC could predict infection better. The "delta" was considered as the changes in the absolute values (subtracting day t0 from day t1) of PCT, CRP, and WBC.This study suggest that early elevation of PCT within the first 24 hours of new onset infection, interpreted with clinical results, appears to be a promising indicator for the diagnosis of infections following LRC.

A rare case of cavitary lung cancer complicated with mycotic pneumonia and bullous emphysema: A case report and review of the literature.

RATIONALE: The accurate diagnosis and staging of cavitary lung cancer is challenging but essential for the choice of therapy; therefore, the differential diagnosis of cystic pulmonary lesions needs to be elucidated. PATIENT CONCERNS: A patient was admitted with multifocal thin-walled cystic lesions in chest computed tomography. DIAGNOSES: The patient had been diagnosed as heterogeneous bullous emphysema pathologically about 3 years ago. His diagnosis turned out to be metastatic cavitary lung cancer complicated with fungal pneumonia this time. INTERVENTIONS: The patient underwent lung volume reduction surgery during his first hospitalization. Concurrent systemic chemotherapy and whole brain radiotherapy were administered after the diagnosis of cystic lung cancer. OUTCOMES: The patient was lost to follow-up after the chemoradiotherapy. LESSONS: Cavitary lung cancer should always be kept in mind during differential diagnosis of pulmonary cystic lesions. Pathological diagnosis by biopsy and surgery could be considered to avoid delayed treatment of malignancy.

hTERT gene polymorphism correlates with the risk and the prognosis of thyroid cancer.

OBJECTIVES: The study explored the association between rs10069690C/T and rs2736100G/T of human telomerase reverse transcriptase (hTERT) gene, and the prognosis of thyroid cancer. METHODS: The study had 452 thyroid cancer patients recruited as case group who hospitalized in Jingzhou Central Hospital from January 2001 to June 2004 and 452 healthy people recruited as control group at the same area. The hTERT gene polymorphisms at rs10069690 C/T and rs2736100 G/T were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between patients' life quality and hTERT gene polymorphisms six months after surgery was evaluated based on the Cancer patients' quality of life index rating scale. RESULTS: There were statistical differences in genotype and allele frequencies of rs10069690 C/T between the case group and control group (both P < 0.05). An association between rs10069690C/T polymorphism and an increased risk of thyroid cancer was shown by logistic regression analysis (CT vs. CC, OR = 1.333, 95%CI = 1.006-1.766, P = 0.045; TT vs. CC, OR = 1.910, 95%CI = 1.084-3.367, P = 0.023; CT + TT vs. CC, OR = 2.246, 95%CI = 1.078-1.840, P = 0.006; T vs. C, OR = 1.376, 95%CI = 1.104-1.715, P = 0.004). Genotype frequency of rs2736100G/T between the two groups had no statistical differences (P > 0.05). After stratification according to age, T stage, tumor size and tumor node metastasis (TNM) stage, the distribution frequencies of CC genotype and CT + TT genotype of rs10069690C/T showed significant difference (P < 0.05). The life quality of patients with CC genotype was better than that of patients with CT $+$ TT genotype. The results of Cox regression model multifactor analysis showed that age, T stage, tumor size and rs10069690C/T were independent risk factors of thyroid cancer prognosis. CONCLUSIONS: hTERT gene polymorphism at rs10069690C/T is associated with the risk and prognosis of thyroid cancer, but hTERT gene polymorphism at rs2736100G/T is not.

Effects of Cold Irrigation on Early Results after Total Knee Arthroplasty: A Randomized, Double-Blind, Controlled Study.

Several studies have indicated that pain peaks at 24 to 48 hours after total knee arthroplasty (TKA) surgery. TKA has been associated with disruption in normal sleep patterns, swelling knee, and significant blood loss. However, a satisfactory regime to resolve these mentioned problems has yet to be found.In this study, a total of 420 patients were randomly allocated into two groups and treated with continuous irrigation of either 4000 mL cold saline with 0.5% epinephrine or normal temperature solution. Clinical outcomes including pain scores at rest during postoperative three days, drainage output, analgesic consumption, decreased hemoglobin, sleep quality, and satisfaction rate were analyzed. Mean scores and postoperative change in scores were calculated.Visual analog scale (VAS) pain scores in the treatment group were significantly reduced from 4 hours (P = 0.0016) to 24 hours (P = 0.0004) after TKA. Additional benefits including reduced analgesic consumption, improved satisfaction rate, and sleep quality were observed. In addition, a significant reduction in blood loss reflected by decreased Hb and drainage was found.In this study, irrigation with a cold 0.5% epinephrine solution was a beneficial and cost-effective treatment that decreased acute postoperative VAS pain scores immediately after and 1 day after surgery. Patients reported postoperative improvement in sleep quality and overall satisfaction rate with a decrease in morphine usage. In addition, a reduction of intraoperative blood loss might decrease the blood transfusion rate and related costs. Collectively, irrigation with cold 0.5% epinephrine offers a safe, simple, and effective treatment that might improve recovery and enhance quality of life of patients undergoing TKA.

Sleep Quality Effects Recovery After Total Knee Arthroplasty (TKA)--A Randomized, Double-Blind, Controlled Study.

This study examined the effects of sleep quality on early recovery after total knee arthroplasty. A total of 148 patients were randomized 1:1 to receive either zolpidem or placebo for 2 weeks. VAS pain scores (rest, ambulation and night), range of motion (ROM), total amount of opioid analgesics and antiemetics taken, postoperative nausea and vomiting (PONV), sleep efficacy and satisfaction were recorded. It was found that patients taking zolpidem achieved greater improvement in quality of life and reported better satisfaction. Patients in the intervention group had lower pain score and took less antiemetics. Moreover, a significant correlation between sleep quality and ROM was detected. These results demonstrated that improved sleep quality is beneficial to patients' post-TKA recovery.