Effects of different doses of remimazolam on hemodynamics during general anesthesia in patients with septic shock.

OBJECTIVE: The stability of hemodynamics plays a vital role in the process of anesthesia induction for patients with septic shock. As a new-type benzodiazepine, remimazolam has numerous advantages, including rapid induction, rapid recovery, stable hemodynamics, and mild respiratory depression. Nevertheless, reports about the effects of remimazolam on hemodynamics in patients with septic shock are still limited. The study aimed to evaluate the effects that different doses of remimazolam have on hemodynamics in inducing general anesthesia in patients with septic shock. PATIENTS AND METHODS: Admitted to the intensive care unit of our hospital from January 2023 to June 2023, 75 patients with septic shock caused by acute appendicitis-induced sepsis were selected as observation subjects. They were randomly assigned to receive low-dose [0.2 mg/(kg·h)], medium-dose [0.3 mg/(kg·h)], and high-dose [0.4 mg/(kg·h)] remimazolam by using a random number table, with 25 patients in each group. Their intraoperative conditions were recorded, including operation duration, intraoperative hemorrhage volume, intraoperative transfusion volume, and decannulation time. Hemodynamic parameters, including mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), and stoke volume index (SVI) were collected at seven-time points (T0: before induction; T1: before intubation; T2: after intubation; T3: the start of operation; T4: 15 min after operation; T5: 30 min after operation; T6: the end of operation). We also compared hepatic and renal function indexes, including blood urea nitrogen (BUN), serum creatinine (sCr), procalcitonin (PCT), white blood cells (WBC), tumor necrosis factor-α2 (TNF-α2), and Interleukin-6 (IL-6), of the three groups of patients before operation and 1, 3, 5, 7 days after operation. In addition, the incidence of adverse reactions in the three groups was recorded and compared. RESULTS: During remimazolam induction, the number of patients with intraoperative need for rescue remimazolam in the medium-dose and high-dose groups was significantly lower than in the low-dose group (p < 0.05). In terms of hemodynamic indexes, MAP in the high-dose group at T2 was lower than that at T0 (p < 0.05), and MAP at T2 was significantly lower in the high-dose group than that in the medium-dose group (p < 0.05). Furthermore, MAP at T4 in the medium-dose and high-dose groups declined compared with the low-dose group (p < 0.05). There were no significant differences in HR, CI, and SVI at different time points among the three groups (p > 0.05), but levels of HR and SVI decreased and CI increased after anesthesia compared with those before operation. Additionally, in comparison with the levels before operation, levels of sCR, BUN, PCT, WBC, TNF-α, and IL-6 were higher on postoperative days 1, 3 (p < 0.05) and lower on postoperative day 7 (p < 0.05). After the operation, both levels of BUN and sCR in the medium-dose and high-dose groups were lower than those in the low-dose group (p < 0.05). CONCLUSIONS: Remimazolam is safe and effective for inducing general anesthesia in patients with septic shock. Low, medium, and high doses of remimazolam can maintain a stable hemodynamic state, and the recovery of hepatic and renal function is certain to depend on the dose.

Consensus for HER2 alterations testing in non-small-cell lung cancer.

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Its alterations, including mutation, amplification and overexpression, could result in oncogenic potential and have been detected in many cancers such as non-small-cell lung cancer (NSCLC). Such alterations are, in general, considered markers of poor prognosis. Anti-HER2 antibody-drug conjugates, e.g. trastuzumab deruxtecan (T-DXd, DS-8201) and disitamab vedotin (RC48), were recently approved for HER2-positive breast and gastric cancers. Meanwhile, several HER2-targeted drugs, such as T-DXd, neratinib, afatinib, poziotinib and pyrotinib, have been evaluated in patients with advanced NSCLC, with several of them demonstrating clinical benefit. Therefore, identifying HER2 alterations is pivotal for NSCLC patients to benefit from these targeted therapies. Recent guidelines on HER2 testing were developed for breast and gastric cancer, however, and have not been fully established for NSCLC. The expert group here reached a consensus on HER2 alteration testing in NSCLC with the focus on clinicopathologic characteristics, therapies, detection methods and diagnostic criteria for HER2-altered NSCLC patients. We hope this consensus could improve the clinical management of NSCLC patients with HER2 alterations.

Multiple Sessions of Entorhinal Cortex Deep Brain Stimulation in C57BL/6J Mice Increases Exploratory Behavior and Hippocampal Neurogenesis.

Deep brain stimulation (DBS) has been a medical intervention for a variety of nervous system diseases and mental diseases. The input of DBS in the entorhinal cortex (EC) regulates the neurophysiological activities in its downstream regions, such as the dentate gyrus (DG) area. EC DBS may play a role in the treatment of diseases through hippocampal neurogenesis. This study we examined the effect of multiple sessions of EC DBS on the regulation of hippocampal neurogenesis. 4-month-old male C57BL/6J mice received bilateral multiple sessions of EC DBS (130 Hz, 90 µs, 100 µA, 1 h/d, 21 days), and the DBS parameters used are close to the high-frequency DBS parameters in clinical studies. The open field test (OFT) was used to test the exploratory behavior of mice, and hippocampal neurogenesis was detected by immunofluorescence staining with anti-doublecortin (DCX). We found that multiple sessions of EC DBS were tolerated in C57BL/6J mice, significantly increased exploratory behavior and the number of DCX-positive neurons in the DG area.Clinical Relevance- Hippocampal neurogenesis may be part of the reason for DBS to improve memory, and the results of this study show that multiple sessions of EC DBS increases exploratory behavior and hippocampal neurogenesis, which is conducive to the application of DBS in nervous system diseases and mental diseases related to memory impairment.

[Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy].

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

Leg-Length Change After Unilateral Unicompartmental Knee Arthroplasty in Varus Knee and Its Clinical Implications.

BACKGROUND: To explore the magnitude of leg-length change after the unilateral index unicompartmental knee arthroplasty (UKA) in varus knee and its influence on clinical outcomes. METHODS: A total of 114 patients with bilateral knee osteoarthritis who underwent unilateral UKA from June 2015 to June 2017 were included and followed up for at least 2 years. The leg length and hip-knee angle were measured on full-length standing films before and after the surgery. Flexion contracture was evaluated using a goniometer with the patient in the standing position preoperatively and postoperatively. Hospital for Special Surgery scores, perceived leg-length discrepancy (pLLD), the occurrence, and the time interval of subsequent contralateral knee arthroplasty were recorded and analyzed. RESULTS: The average leg length increased after UKA was 9.39 ± 11.24 mm (range -21.00 to 33.79 mm), and 90 (78.9%) patients showed an increase in the leg length. 35 patients had LLD (defined as ≥10 mm), and 25 presented pLLD preoperatively; 25 patients had LLD, and 45 were suspected with pLLD postoperatively. At the last follow-up, 26 patients underwent subsequent contralateral knee arthroplasty. Postoperative LLD and pLLD were not associated with Hospital for Special Surgery scores of UKA but associated with subsequent contralateral knee arthroplasty. CONCLUSIONS: LLD and pLLD were common in patients both before and after UKA. Most patients showed leg lengthening after UKA. Postoperative LLD and pLLD were not associated with functional scores but associated with a subsequent contralateral knee arthroplasty.

Cerebral blood microcirculation measurement in APP/PS1 double transgenic mice at the preclinical stage of Alzheimer's disease: preliminary data on the early intervention of anodal transcranial direct current stimulation.

Anodal transcranial direct current stimulation (AtDCS) can improve memory and cognitive dysfunction in patients with Alzheimer's disease (AD), which has been proven in basic and clinical studies. Intervention of AD in preclinical stage is important to prevent progression of AD in the aging society. At the same time, there is increasing evidence that a close link exists between cerebrovascular dysfunction and AD disease. Here we investigated the changes of local cerebral blood microcirculation in preclinical AD mouse model after AtDCS based on the previous studies. Twenty-four 6-month-old male APP/PS1 double transgenic mice were randomly divided into three groups: a model group (AD), a model sham stimulation (ADST) group and a model stimulation group (ATD). Eight 6-month-old male C57 wild-type mice served as a control group (CTL). Mice in the ATD group received 10 AtDCS sessions. Two months after the end of AtDCS in the ATD group, the microcirculation parameters of the frontal cortex of the mice in each group, including cerebral blood flow (CBF), blood flow velocity (Velo), oxygen saturation (SO2) and relative hemoglobin content (rHb), were obtained by the non-invasive laser-Doppler spectrophotometry system "Oxygen-to-See (O2C)". The results showed that AtDCS increased CBF, Velo and SO2, and reduce rHb in APP/PS1 double transgenic mice at the preclinical stage of AD.Clinical Relevance-This shows the positive effect of AtDCS on preclinical AD in cerebrovascular function, and provides effective basic research facts for AtDCS to intervene and delay the clinical application of AD disease.

[Prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in locally advanced non-small cell lung cancer patients treated with thoracic radiation].

Objective: The aim of this retrospective study was to evaluate the prognostic significance of pretreatment Neutrophil-to-Lymphocyte Ratio(NLR) in locally advanced non-small cell lung cancer(NSCLC) patients treated with thoracic radiotherapy. Methods: We retrospectively analyze 420 patients who received thoracic radiotherapy alone, sequential chemoraiotherapy or concurrent chemoradiotherapy for locally advanced stage NSCLC from January 2007 to December 2010 of our hospital. The patients were divided into two groups (high NLR group and low NLR group) with appropriate cutoff point using the receiver operating characteristic (ROC) curve method. The survival curve was established by Kaplan-Meier method. The Log-rank test was used to compare the survival of the two NLR groups and the multivariate analysis was carried out by Cox regression model. Results: Among the 420 patients, 99 received radiotherapy alone, 139 received sequential chemoradiotherapy and 182 received concurrent chemoradiotherapy. 345 patients died and 75 were still alive. The median follow-up time was 5.2 years and the median overall survival was 22 months. The cut-off value of pretreatment NLR was 2.1. The 5-year PFS and OS rates in high NLR group and low NLR group were 10.6% vs 15.7% (P=0.033) and 15.5% vs 22.7% (P=0.012). Multivariate analysis confirmed that pretreatment NLR (hazard ratio 1.06, P=0.041) was independent prognostic factor of OS. Conclusions: Our study revealed that the pretreatment NLR is the independent prognostic factor of OS in patients with locally advanced stage NSCLC treated with thoracic radiotherapy. However, NLR is still greatly influenced by patient's condition and treatment which needs further research.

Long-term renal outcomes in multi-ethnic Southeast Asians with lupus nephritis: a retrospective cohort study.

BACKGROUND: Renal involvement is common among Asians with systemic lupus erythematosus and long-term renal outcomes have been described in homogeneous Caucasian and East Asian populations with lupus nephritis, but data are scarce for other ethnicities. AIM: To evaluate the incidence and risk factors for progressive chronic kidney disease (CKD) in multi-ethnic Southeast Asians with lupus nephritis. METHODS: This is a single-centre retrospective cohort study of adults with biopsy-proven lupus nephritis diagnosed between May 2001 and May 2009. Demographic and clinical data were retrieved from electronic medical records. Patients were excluded if baseline comorbid, renal function or pharmacotherapy data were incomplete or if they default follow-up within 3 months from time of diagnosis. Primary outcome was progressive CKD, defined by end-stage renal disease or persistent doubling of serum creatinine or reduction in eGFR ≥50% for ≥3 months from baseline. RESULTS: We studied 113 patients with newly diagnosed biopsy-proven lupus nephritis. Median age was 42 (interquartile range 29-52) years; the majority were Chinese (76%; Malay 13% and others 11%) and female (81%). Two-thirds had International Society of Nephrology and Renal Pathology Society Class III or IV nephritis; serum creatinine was 86 (67-125) µmol/L with heavy proteinuria (6.3 (2.5-12.2) g/g creatinine). Median follow-up was 110 (83-142) months. Remission (partial and complete) occurred in 96% at 3.1 (1.6-5.2) months after diagnosis. Among patients who achieved remission, 56% had disease relapse at 19.0 (6.0-40.2) months after remission. Patients with progressive CKD (n = 13, 11%) had lower baseline CKD Epidemiology Collaboration estimated glomerular filtration rate (37.3 (16.5-82.0) vs 79.4 (57.5-101.0) mL/min/1.73 m2 , P = 0.03) and higher chronicity index (5 (3-6) vs 3 (2-3), P = 0.04) than those who did not. Remission, early remission within 6 months, complete remission and non-relapse were less frequently associated with progressive CKD (P < 0.01). CONCLUSION: Multi-ethnic Southeast Asians with biopsy-proven lupus nephritis had high remission rates and low incidence of progressive CKD. Progressive CKD was associated with poorer baseline renal function, higher histological chronicity index, failure to achieve remission and occurrence of relapse.

The clinical significance of KIT mutations in melanoma: a meta-analysis.

This study aimed to evaluate the association of KIT mutations with clinicopathologic features of melanomas using a meta-analysis and to identify differences between Asian and White populations using subgroup analyses. We selected 32 studies from the literature including 5224 patients. The pooled data were combined, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Heterogeneity and publication bias were also determined. KIT mutations were reported in 497 (9.5%) of 5224 patients with melanomas, and were associated significantly with age, clinical melanoma subtype, anatomic location, and chronic sun-damage (CSD), but not with sex, histological type, Breslow thickness, ulceration, mitotic rate, or tumor stage. The incidence of KIT mutation was significantly higher in older individuals (OR=1.296, 95% CI: 1.025-1.641; P=0.031), and showed a positive association with mucosal melanoma (OR=1.363, 95% CI: 1.094-1.697; P=0.006), acral melanoma (OR=1.374, 95% CI: 1.123-1.682; P=0.02), and CSD (OR=1.880, 95% CI: 1.127-3.136; P=0.016), but a negative relationship with melanomas arising in non-CSD skin (OR=0.562, 95% CI: 0.392-0.805; P=0.002). The frequency of KIT mutations was associated negatively with melanomas located on the extremities. KIT mutations, which are critical in the genetic pathogenesis of melanomas, define a unique subtype of melanoma associated closely with older age, and acral, mucosal, or CSD sites, but not associated with any histological features or tumor stage. Although the KIT mutation rate is higher in White than Asian populations, no significant difference in clinical association with KIT mutations was detected between the two groups.

Assessment of obestatin and arginine vasopressin (AVP) levels in acute renal failure and acute heart failure.

OBJECTIVE: We conducted this study to assess the clinical application of obestatin and arginine vasopressin (AVP) levels in cases of acute renal failure (ARF) and acute heart failure (AHF). PATIENTS AND METHODS: 30 cases of ARF, 30 cases of AHF, 30 cases of ARF complicated with AHF, and 30 cases of healthy subjects (control group) were successively selected. An ELISA test was conducted to detect levels of obestatin and AVP. Routine biochemistry testing was applied to detect the levels of serum creatinine and calculate the glomerular filtration rate (GFR). Electrochemiluminescence double antibody sandwich fluorescence immune testing was applied to detect NT-proBNP and color Doppler ultrasound diagnostic apparatus was applied to detect renal arterial resistive index (RI) and left ventricular ejection fraction (LVEF). The 30-day mortality was documented. RESULTS: Compared to other groups, the group of patients suffering from ARF complicated with AHF had significantly higher levels of obestatin and AVP, and significantly higher levels of serum creatinine, NT-proBNP and RI; however, their GFR and LVEF levels were the lowest. Differences were statistically significant (p < 0.05). Levels of obestatin and AVP are positively correlated with serum creatinine, NT-proBNP and RI levels, but negatively correlated with GFR and LVEF levels. The mortality rate of the group suffering from ARF complicated with AHF was markedly increased (p = 0.035). The obestatin and AVP levels of the death group were significantly higher than that of the survival group. However, the comparison among levels of serum creatinine, GFR, NT-proBNP, RI and LVEF revealed no statistical significance (p > 0.05). CONCLUSIONS: Obestatin and AVP levels were closely related to the severity of ARF and AHF and survival prognosis, which could be a sensitive indicator for diagnoses and prognoses.

Hepatic Tm6sf2 overexpression affects cellular ApoB-trafficking, plasma lipid levels, hepatic steatosis and atherosclerosis.

The human transmembrane 6 superfamily member 2 (TM6SF2) gene has been implicated in plasma lipoprotein metabolism, alcoholic and non-alcoholic fatty liver disease and myocardial infarction in multiple genome-wide association studies. To investigate the role of Tm6sf2 in metabolic homeostasis, we generated mice with elevated expression using adeno-associated virus (AAV)-mediated gene delivery. Hepatic overexpression of mouse Tm6sf2 resulted in phenotypes previously observed in Tm6sf2-deficient mice including reduced plasma lipid levels, diminished hepatic triglycerides secretion and increased hepatosteatosis. Furthermore, increased hepatic Tm6sf2 expression protected against the development of atherosclerosis in LDL-receptor/ApoB48-deficient mice. In cultured human hepatocytes, Tm6sf2 overexpression reduced apolipoprotein B secretion and resulted in its accumulation within the endoplasmic reticulum (ER) suggesting impaired ER-to-Golgi trafficking of pre-very low-density lipoprotein (VLDL) particles. Analysis of two metabolic trait-associated coding polymorphisms in the human TM6SF2 gene (rs58542926 and rs187429064) revealed that both variants impact TM6SF2 expression by affecting the rate of protein turnover. These data demonstrate that rs58542926 (E167K) and rs187429064 (L156P) are functional variants and suggest that they influence metabolic traits through altered TM6SF2 protein stability. Taken together, our results indicate that cellular Tm6sf2 level is an important determinant of VLDL metabolism and further implicate TM6SF2 as a causative gene underlying metabolic disease and trait associations at the 19p13.11 locus.

Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a Chinese girl with Fanconi Anemia.

Fanconi Anemia (FA) is a rare genetically heterogeneous disorder with 17 known complement groups caused by mutations in different genes. FA complementation group L (FA-L, OMIM #608111) occurred in 0.2% of all FA and only eight mutant variants in the FANCL gene were documented. Phenotype and genotype correlation in FANCL associated FA is still obscure. Here we describe a Chinese girl with FA-L caused by a novel homozygous mutation c.822_823insCTTTCAGG (p.Asp275LeufsX13) in the FANCL gene. The patient's clinical course was typical for FA with progression to bone marrow failure, and death from acute myelomonocytic leukemia (AML-M4) at 9 years of age. Mutation analysis also detected a likely somatic c.2608G > A (p.Gly870Ser) in the SETBP1 gene. Consistent copy number losses of 7q and 18p and gains of 3q and 21q and accumulated non-clonal single cell chromosomal abnormalities were detected in blood leukocytes as her FA progressed. This is the first Chinese FA-L case caused by a novel FANCL mutation. The somatic gene mutation and copy number aberrations could be used to monitor disease progression and the clinical findings provide further information for genotype-phenotype correlation for FA-L.

Research progress about effects of myocardial enzyme and troponin on uremia with acute left ventricular failure.

OBJECTIVE: We studied the diagnostic value of CK-MB and troponin (cTnI) in uremia with acute left ventricular failure patients. PATIENTS AND METHODS: We enrolled 130 uremia patients with maintenance hemodialysis (MHD) and divided them into two groups: (i) the observation group with patients suffering from acute left ventricular failure (n=30) and (ii) the control group which contained cases without acute left ventricular failure (n=100). We verified CK-MB, cTnI, serum creatinine, blood urea nitrogen, pro-BNP and LVEF levels at 6 h, 12 h, 24 h, 48 h, 72 h, 7 d and 14 d after the attack and carried out 1-year follow-up to compare total mortality and cardiogenic mortality. RESULTS: Our results showed that CK-MB and cTnI levels in the observation group were significantly higher than those in the control group (p<0.05). CK-MB and cTnI in the observation group increased into platform stage slowly with no peak or downtrend. They were in a linear pattern in the control group. Comparison of SCr and BUN in two groups at different time points produced no statistically significant differences (p>0.05). Pro-BNP levels in the hospital as well as 1 month, 6 months and 12 months follow-ups were higher than those in the control group, and differences were of statistical significant (p<0.05). While in hospital LVEF level in the observation group was higher than that in the other group, differences regarding 1 month, 6 months and 12 months follow-up between two groups had no statistical significance (p>0.05). Total mortality and cardiogenic mortality in the observation group were higher than those in the control group, and differences were statistically significant (p<0.05). CONCLUSIONS: CK-MB, cTnI, SCr, BUN, pro-BNP and LVEF were independent risk factors for total mortality while CK-MB, cTnI and pro-BNP were independent risk factors for cardiogenic mortality.

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial.

Background: The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients and methods: Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. Results: A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%-28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55-1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). Conclusion: EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. Trial registration ID: NCT01494558.

[IMRT-based preoperative neoadjuvant chemoradiotherapy for thoracic esophageal squamous cell carcinoma (ESCC): an analysis of outcome and prognosis].

OBJECTIVE: To analyze the outcome and prognostic factors of IMRT-based preoperative neoadjuvant chemoradiotherapy in patients with thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Clinical data of 62 patients with thoracic ESCC who received IMRT-based neoajuvant chemoradiotherapy from January 2009 to January 2015 were retrospectively analyzed. The radiation therapy was given 1.8-2 Gy/fraction per day over 5 days per week with 6 MV X-rays, and then all patients underwent esophagectomy and lymphadenectomy. RESULTS: Among the 62 patients, the R0 resection rate was 96.8%. Twenty (32.3%) patients achieved pCR and 56 (90.3%) cases got down-staging. Grade Ⅲ marrow suppression and esophagitis were seen in 8 (12.9%) and 2 (3.2%) patients, respectively. Eleven (17.7%) patients experienced postoperative complications and three died. The median follow-up was 27 months. The 1-, 3- and 5-year overall survival rates were 88.0%, 63.3% and 44.2%, respectively, with a corresponding disease-free survival rate of 68.1%, 54.8%, and 43.9%, respectively.The univariate analysis showed that pre-treatment stage Ⅱ, down-staging, T/N pCR, good tumor response to neoadjuvant chemoradiotherapy, pN0 and R0 resection were favorable prognostic factors (P<0.05). The multivariate analyses indicated that pre-treatment stage was an independent prognostic factor. CONCLUSIONS: For patients with thoracic ESCC, IMRT-based neoadjuvant chemoradiotherapy followed by surgery can achieve a higher R0 resection rate, down-staging rate, higher pCR rate, and a better tolerance. The incidence of postoperative complications is low. Pre-treatment stage, down-staging, pathological tumor response, lymph node status and R0 resection results are prognostic factors, and the pre-treatment stage is an independent prognostic factor.

[Technical advancement improves survival in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiotherapy].

OBJECTIVE: This study aimed to evaluate the impact of technical advancement of radiation therapy in patients with LA-NSCLC receiving definitive radiotherapy (RT). METHODS: Patients treated with definitive RT (≥50 Gy) between 2000 and 2010 were retrospectively reviewed. Overall survival (OS), cancer specific survival (CSS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were calculated and compared among patients irradiated with different techniques. Radiation-induced lung injury (RILI) and esophageal injury (RIEI) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 (NCI-CTCAE 3.0). RESULTS: A total of 946 patients were eligible for analysis, including 288 treated with two-dimensional radiotherapy (2D-RT), 209 with three-dimensional conformal radiation therapy (3D-CRT) and 449 with intensity-modulated radiation therapy (IMRT) respectively. The median follow-up time for the whole population was 84.1 months. The median OS of 2D-RT, 3D-CRT and IMRT groups were 15.8, 19.7 and 23.3 months, respectively, with the corresponding 5-year survival rate of 8.7%, 13.0% and 18.8%, respectively (P<0.001). The univariate analysis demonstrated significantly inferior OS, LRPFS, DMFS and PFS of 2D-RT than those provided by 3D-CRT or IMRT. The univariate analysis also revealed that the IMRT group had significantly loger LRPFS and a trend toward better OS and DMFS compared with 3D-CRT. Multivariate analysis showed that TNM stage, RT technique and KPS were independent factors correlated with all survival indexes. Compared with 2D-RT, the utilization of IMRT was associated with significantly improved OS, LRPFS, DMFS as well as PFS. Compared with 3D-CRT, IMRT provided superior DMFS (P=0.035), a trend approaching significance with regard to LRPFS (P=0.073) but no statistically significant improvement on OS, CSS and PFS in multivariate analysis. The incidence rates of RILI were significantly decreased in the IMRT group (29.3% vs. 26.6% vs.14.0%, P<0.001) whereas that of RIET rates were similar (34.7% vs. 29.7% vs. 35.3%, P=0.342) among the three groups. CONCLUSIONS: Radiation therapy technique is a factor affecting prognosis of LA-NSCLC patients. Advanced radiation therapy technique is associated with improved tumor control and survival, and decreased radiation-induced lung toxicity.

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant.

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.