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Robotic versus laparoscopic left colectomy with complete mesocolic excision for left-sided colon cancer: a multicentre study with propensity score matching analysis

Zheng, H; Wang, Q; Fu, T; Wei, Z; Ye, J; Huang, B; Li, C; Liu, B; Zhang, A; Li, F; Gao, F; Tong, W
BACKGROUND:Robotic surgery for right-sided colon and rectal cancer has rapidly increased; however, there is limited evidence in the literature of advantages of robotic left colectomy (RLC) for left-sided colon cancer. The purpose of this study was to compare the outcomes of RLC versus laparoscopic left colectomy (LLC) with complete mesocolic excision (CME) for left-sided colon cancer. METHODS:Patients who had RLC or LLC with CME for left-sided colon cancer at 5 hospitals in China between January 2014 and April 2022 were included. A one-to-one propensity score matched analysis was performed to decrease confounding. The primary outcome was postoperative complications occurring within 30 days of surgery. Secondary outcomes were disease-free survival, overall survival and the number of harvested lymph nodes. RESULTS:A total of 292 patients (187 males; median age 61.0 [20.0-85.0] years) were eligible for this study, and propensity score matching yielded 102 patients in each group. The clinical-pathological characteristics were well-matched between groups. The two groups did not differ in estimated blood loss, conversion to open rate, time to first flatus, reoperation rate, or postoperative length of hospital stay (p > 0.05). RLC was associated with a longer operation time (192.9 ± 53.2 vs. 168.9 ± 52.8 minutes, p=0.001). The incidence of postoperative complications did not differ between the RLC and LLC groups (18.6% vs. 17.6%, p = 0.856). The total number of lymph nodes harvested in the RLC group was higher than that in the LLC group (15.7 ± 8.3 vs. 12.1 ± 5.9, p< 0.001). There were no significant differences in 3-year and 5-year overall survival or 3-year and 5-year disease-free survival. CONCLUSIONS:Compared to laparoscopic surgery, RLC with CME for left-sided colon cancer was found to be associated with higher numbers of lymph nodes harvested and similar postoperative complications and long-term survival outcomes.
PMID: 36964884
ISSN: 1128-045x
CID: 5533132

Circumsporozoite protein suppresses the IFN-gamma-mediated killing of Plasmodium liver stage through enhanced autophagy related proteins ubiquitination [Meeting Abstract]

Zheng, H; Lu, X; Li, K; Zhu, F; Liu, T; Ding, Y; Fu, Y; Zhang, K; Rodriguez, A; Dai, J; Wu, Y; Xu, W
Malaria is still one of the most devastating diseases worldwide, which is caused by infection of the genus Plasmodium. Liver stage is an essential early step of malaria parasite infection, and plasmodium replicates in parasitophorous vacuole (PV) of hepatocytes at this stage. Although encountering with hepatocyte autonomous immunity, exoerythrocytic forms (EEFs) in PV can still survive and successfully complete infection of hepatocytes. The underlying mechanism is largely unknown. Here, we show that sporozoite circumsporozoite protein (CSP) translocates from the parasitophorous vacuole into the hepatocyte cytoplasm to significantly inhibit the killing of exoerythrocytic forms (EEFs) by interferon-gamma (IFN-gamma). Nitric oxide were found to be indispensable for the resistance to IFN-gamma-mediated killing of EEFs by CSP. Attenuation of the IFN-gamma-mediated killing of EEFs by CSP is dependent on its ability to reduce the levels of ATGs in hepatocytes. The ATGs downregulation occurs through its enhanced ubiquitination mediated by E3 ligase NEDD4, an enzyme that is upregulated by CSP when it translocates from the cytoplasm into the nucleus of hepatocytes via its NLS domain. Thus, we have revealed an unrecognized role of CSP in suppressing host autonomous immunity, and shed new light for a prophylaxis strategy against liver-stage infection
EMBASE:631545479
ISSN: 1521-4141
CID: 4414712

Predictable variability in sensory-evoked responses in the awake brain: Optimal readouts and implications for behavior [Meeting Abstract]

Sederberg, A; Pala, A; Zheng, H; He, B; Stanley, G
In a near-threshold sensory detection task, an animal sometimes detects and sometimes misses the same physical stimulus. A simple hypothesis is that perceptual variability is linked to variability in sensory-evoked responses in the brain as early as primary cortex. Response variability arises in part from the interaction of sensory (Figure presented) inputs with ongoing activity and is partially predictable based on the pre-stimulus cortical state. If variability in evoked responses is linked to perception, and if that variability is predictable, we would expect that it would be possible to predict based on ongoing activity whether sensory cortex is primed to detect a sensory input. Here, we determine the pre-stimulus features that are predictive of variability in the evoked response in the awake animal. We then ask what implications these observations have for the detectability of a stimulus. Using data obtained from multi-electrode recordings across the cortical depth in S1 of awake mice, we systematically quantify how much variability in the sensory-evoked LFP response is predictable from ongoing LFP activity (Fig. 1AB). This interaction has been studied extensively in the anesthetized animal [e.g., 1, 2], where the major predictors of response variability are the degree of cortical synchronization, quantified by the amount of low-frequency power, and the phase of low-frequency oscillations at which sensory input occurred. Similarly, we found that the degree of synchronization was predictive, but instead of oscillation phase, the instantaneous level of activation of the LFP in layer 4 was a useful predictor. Specifically, positive excursions in the LFP and more low-frequency (1-5 Hz) power in the LFP in the pre-stimulus period predicted larger sensory-evoked responses ("high-response state"). Using a regularized estimator of current-source density (CSD) [3] on single trials, we localized the most predictive ongoing signal to a current source location near layer 4. Finally, we found that no significant predictive power was gained by increasing the complexity of the decoder or by utilizing the full array of channels. Thus, the most predictive signatures of ongoing activity are remarkably simple and could be accessible to downstream areas. Next, we examined the impact of predictable variability on an ideal observer analysis of the detectability of sensory events (Fig. 1C). We built a detection model, in which the detection threshold is either fixed, or adaptive and based on the pre-stimulus features that are predictive of evoked variability. We quantified the accuracy of the model in terms of the simulated hit rate and the false alarm rate. Detection was more accurate in the adaptive threshold model. In the fixed-threshold model, pre-stimulus features predicted hit and miss trials. This relationship was weaker in the adaptive- threshold model, where hits as well as false alarms were nearly equally as likely to occur in low- or high-response state. In summary, if sensory perception is built on the cortical response and variability in this response is completely unpredictable, then perceptual variability would to some extent be determined by cortical variability. However, if cortical variability is predictable and downstream circuits in the brain make this prediction, then the perceptual variability could be decoupled from cortical variability
EMBASE:627390708
ISSN: 1471-2202
CID: 3831042

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease

Zhu, H; Wang, X; Wallack, M; Li, H; Carreras, I; Dedeoglu, A; Hur, J-Y; Zheng, H; Li, H; Fine, R; Mwamburi, M; Sun, X; Kowall, N; Stern, R A; Qiu, W Q
Amylin, a pancreatic peptide, and amyloid-beta peptides (Abeta), a major component of Alzheimer's disease (AD) brain, share similar beta-sheet secondary structures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain. Using AD mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD pathogenesis. Surprisingly, chronic intraperitoneal (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well as lowers the concentrations of Abeta in the brain. These treatments significantly improve their learning and memory assessed by two behavioral tests, Y maze and Morris water maze. Both amylin and pramlintide treatments increase the concentrations of Abeta1-42 in cerebral spinal fluid (CSF). A single i.p. injection of either peptide also induces a surge of Abeta in the serum, the magnitude of which is proportionate to the amount of Abeta in brain tissue. One intracerebroventricular injection of amylin induces a more significant surge in serum Abeta than one i.p. injection of the peptide. In 330 human plasma samples, a positive association between amylin and Abeta1-42 as well as Abeta1-40 is found only in patients with AD or amnestic mild cognitive impairment. As amylin readily crosses the blood-brain barrier, our study demonstrates that peripheral amylin's action on the central nervous system results in translocation of Abeta from the brain into the CSF and blood that could be an explanation for a positive relationship between amylin and Abeta in blood. As naturally occurring amylin may play a role in regulating Abeta in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.
PMCID:4161670
PMID: 24614496
ISSN: 1359-4184
CID: 1480932

Prognostic role of al amyloid deposition in vasculature [Meeting Abstract]

Zheng, H; Mazumder, A; Katz, S
Background: Vasculature involvement of AL amyloid or amyloid fibrils has been commonly reported in tissue biopsy. However, the prognostic role of vasculature involvement has not been studied. Methods: Tissue biopsies of patients with biopsy-proven AL amyloidosis were reviewed between 2006 to 2011. Tissue and vasculature involvement were recorded from Congo red staining and/or electronic microscopic detection of amyloid fibrils in tissue and/or capillaries. Amyloid deposition in vasculature was defined as Congo red staining of small vessels and fibrils deposition in capillaries under electronic microscope. EKG and echocardiography at the time of diagnosis were reviewed. NCCN Guidelines Version 1.2012 was used for reassessing cardiac involvement for all patients. Death was censored till November 30, 2011. Results: 28 patients with biopsy data available were included for the analysis. Mean age was 64.8 +/- 9.9 years. All patients had at least one organ biopsy with tissue Congo Red staining positive. 18 patients with positive amyloid deposition in vasculature (V positive), 14 (77.8%) had cardiac involvement based on NCCN criteria; 10 patients with negative amyloid deposition (V negative), 4 (40%) had cardiac involvement (P<0.01). LV wall thickness and LV filling pressure (E/e') were significantly increased in V positive group comparing with V negative group (15 mm +/- 0.07 vs 1.1 mm +/- 0.07; 21.6 +/-1.7 vs 11 +/-1.7 respectively, both P = 0.002). 7 cases in V positive group had pericardial effusion comparing 0 case in V negative group (P = 0.03). 12 cases with low voltage from ECG in V positive group comparing with 3 cases in V negative group (P = 0.03). LV ejection fraction, left atrium size, pulmonary pressure, troponin I and NT-ProBNP levels were not significantly different between two groups. Mortality rate in V positive group (10/18, 55.6%) was significantly higher comparing with V negative group (2/10, 20%) (P = 0.04) Conclusions: The patients with positive amyloid deposition in vasculature !
EMBASE:71020606
ISSN: 0735-1097
CID: 288182

Pulmonary hypertension in POEMS syndrome

Li, Jian; Tian, Zhuang; Zheng, Hao-Yi; Zhang, Wei; Duan, Ming-Hui; Liu, Yong-Tai; Cao, Xin-Xin; Zhou, Dao-Bin
POEMS syndrome is a rare clonal plasma cell disease. Patients with POEMS syndrome are at risk of developing pulmonary hypertension, but the data on its incidence and impact on outcome are limited. We reviewed records of 154 POEMS syndrome patients with complete duplex echocardiography data for estimation of pulmonary artery systolic pressure (sPAP) at the time of diagnosis. Forty-two (27%) of 154 patients with pulmonary hypertension (estimated sPAP >/=50 mmHg) were identified. Median age was 46 years (range 31-71 years). Patients with pulmonary hypertension were more likely to have peripheral edema (P=0.04), ascites (P=0.02), pleural effusion (P=0.005), and have longer time from onset to diagnosis (P=0.004) when compared with those without pulmonary hypertension. Restrictive abnormalities and decreased diffusion capacity of carbon monoxide were observed in 83% and 96% patients with pulmonary hypertension, compared with 50% and 72% in patients without pulmonary hypertension, respectively. Reversibility of pulmonary hypertension was observed after treatment of POEMS syndrome. After median follow of 32 months, survival of patients with pulmonary hypertension was worse than those without (median overall survival 54 months vs. median not reached, P=0.021). In conclusion, pulmonary hypertension is a common feature of POEMS syndrome, and is associated with signs of extravascular volume overload. Although active treatment of POEMS syndrome can reverse pulmonary hypertension, survival of these patients is worse than those without pulmonary hypertension.
PMCID:3659947
PMID: 22983590
ISSN: 0390-6078
CID: 288882

Cardiac Effects of Cancer Therapy

Chapter by: Zheng, H; Kobrinsky, B; Katz, S; Speyer, JL
in: Abeloff's clinical oncology by
Philadelphia, PA : Churchill Livingstone/Elsevier, c2013
pp. 858-873.e5
ISBN: 9780323222112
CID: 1843162

Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma

Zheng, H; Ying, H; Yan, H; Kimmelman, A C; Hiller, D J; Chen, A-J; Perry, S R; Tonon, G; Chu, G C; Ding, Z; Stommel, J M; Dunn, K L; Wiedemeyer, R; You, M J; Brennan, C; Wang, Y A; Ligon, K L; Wong, W H; Chin, L; dePinho, R A
Glioblastoma (GBM) is a highly lethal primary brain cancer with hallmark features of diffuse invasion, intense apoptosis resistance and florid necrosis, robust angiogenesis, and an immature profile with developmental plasticity. In the course of assessing the developmental consequences of central nervous system (CNS)-specific deletion of p53 and Pten, we observed a penetrant acute-onset malignant glioma phenotype with striking clinical, pathological, and molecular resemblance to primary GBM in humans. This primary, as opposed to secondary, GBM presentation in the mouse prompted genetic analysis of human primary GBM samples that revealed combined p53 and Pten mutations as the most common tumor suppressor defects in primary GBM. On the mechanistic level, the "multiforme" histopathological presentation and immature differentiation marker profile of the murine tumors motivated transcriptomic promoter-binding element and functional studies of neural stem cells (NSCs), which revealed that dual, but not singular, inactivation of p53 and Pten promotes cellular c-Myc activation. This increased c-Myc activity is associated not only with impaired differentiation, enhanced self-renewal capacity of NSCs, and tumor-initiating cells (TICs), but also with maintenance of TIC tumorigenic potential. Together, these murine studies have provided a highly faithful model of primary GBM, revealed a common tumor suppressor mutational pattern in human disease, and established c-Myc as a key component of p53 and Pten cooperative actions in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal, and tumorigenic potential.
PMID: 19150964
ISSN: 1943-4456
CID: 1979722

Insulin sensitivity, vascular function, and iron stores in voluntary blood donors

Zheng, Haoyi; Patel, Milan; Cable, Ritchard; Young, Lawrence; Katz, Stuart D
OBJECTIVE: Reduced iron stores after blood donation are associated with improved vascular function and decreased cardiovascular risk. We sought to determine whether iron-dependent changes in glucose metabolism may contribute to improved vascular function in blood donors. RESEARCH DESIGN AND METHODS: We conducted a prospective cross-sectional study in 21 high-frequency blood donors (more than eight donations in the last 2 years) and 21 low-frequency blood donors (one to two donations in the last 2 years) aged 50-75 years. Serum markers of iron stores, whole-body insulin sensitivity index (WBISI) during oral glucose tolerance testing, and flow-mediated dilation in the brachial artery were determined in all subjects. RESULTS: Serum ferritin was decreased (median values 23 vs. 36 ng/ml, P < 0.05) and flow-mediated dilation in the brachial artery was increased (median values 5.9 vs. 5.3%, P < 0.05) in high-frequency donors compared with low-frequency donors, respectively, but WBISI (median values 4.8 vs. 4.7) and related measures of glucose tolerance did not differ between groups. Flow-mediated dilation significantly decreased at 1 h after oral glucose loading in both groups, but the decrease in flow-mediated dilation at 1 h did not differ between high- and low-frequency donors. CONCLUSIONS: High-frequency blood donation reduced serum ferritin and increased flow-mediated dilation compared with low-frequency donation but did not improve insulin sensitivity or protect the vascular endothelium from the adverse effects of acute hyperglycemia after oral glucose loading. These findings suggest that the mechanisms linking blood donation to improved vascular function are not likely related to changes in glucose metabolism
PMID: 17630263
ISSN: 1935-5548
CID: 83243

Association of extended work shifts, vascular function, and inflammatory markers in internal medicine residents: a randomized crossover trial [Letter]

Zheng, Haoyi; Patel, Milan; Hryniewicz, Katarzyna; Katz, Stuart D
PMID: 16954481
ISSN: 1538-3598
CID: 83226