SARS-CoV-2 specific plasma cells acquire the phenotype of long-lived plasma cells in the human bone marrow

Establishment of long-lived plasma cells (PC) in the bone marrow (BM) is important for the development of long-term specific humoral immunity. While SARS-CoV-2-specific, resting, affinity-matured, IgG-secreting plasma cells were described in human bone marrow approx. 6-7 months after infection or vaccination, the long-term durability of these PC remains unclear. We here show that approximately 20% of SARS-CoV-2-specific human BM plasma cells, including RBD-specific PC accommodate the phenotype of long-lived plasma cells, characterized by the lack of CD19 and/or CD45. This result provides evidence in support of the emergence of persistent SARS-CoV-2 specific plasma cells in humans sustaining the durable production of specific serum IgG protecting against severe courses of COVID-19.

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathogenesis, and it remains unclear if T cells also contribute to disease pathology. Here, we combined single-cell transcriptomics and proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Age-dependent generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. The proportion of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a correlated with clinical outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

Influence of Perceptual and Conceptual Information on Fear Generalization: A Behavioral and Event-Related Potential Study.

Learned fear can be generalized through both perceptual and conceptual information. This study investigated how perceptual and conceptual similarities influence this generalization process. Twenty-three healthy volunteers completed a fear-generalization test as brain activity was recorded in the form of event-related potentials (ERPs). Participants were exposed to a de novo fear acquisition paradigm with four categories of conditioned stimuli (CS): two conceptual cues (animals and furniture); and two perceptual cues (blue and purple shapes). Animals (C+) and purple shapes (P+) were paired with the unconditioned stimulus (US), whereas furniture (C-) and blue shapes (P-) never were. The generalized stimuli were thus blue animals (C+P+, determined danger), blue furniture (C-P+, perceptual danger), purple animals (C+P-, conceptual danger), and purple furniture (C-P-, determined safe). We found that perceptual cues elicited larger fear responses and shorter reaction times than did conceptual cues during fear acquisition. This suggests that a perceptually related pathway might evoke greater fear than a conceptually based route. During generalization, participants were more afraid of C+ exemplars than of C- exemplars. Furthermore, C+ trials elicited greater N400 amplitudes. Thus, participants appear able to use conceptually based cues to infer the value of the current stimuli. Additionally, compared with C+ exemplars, we found an enhanced late positive potential effect in response to C- exemplars, which seems to reflect a late inhibitory process and might index safety learning. These findings may offer new insights into the pathological mechanism of anxiety disorders.

Quality of vision and vision-related quality of life after Descemet membrane endothelial keratoplasty: a randomized clinical trial.

PURPOSE: To compare quality of vision and vision-related quality of life (QOL) in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) or ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Fifty-four eyes of 54 patients with Fuchs' dystrophy from six corneal clinics in the Netherlands were randomized to DMEK or ultrathin DSAEK and examined preoperatively, and 3, 6 and 12 months postoperatively. Main outcome measures were corneal higher-order aberrations (HOAs), contrast sensitivity, straylight and vision-related QOL. RESULTS: Posterior corneal HOAs decreased after DMEK and increased after ultrathin DSAEK (p ≤ 0.001) 3 months after surgery and correlated positively with best spectacle-corrected visual acuity (12 months: r = 0.29, p = 0.04). Anterior and total corneal HOAs did not differ significantly between both techniques at any time point. Contrast sensitivity was better (p = 0.01), and straylight was lower (p = 0.01) 3 months after DMEK compared with ultrathin DSAEK; 95% confidence interval [CI] of log(cs) 1.10-1.35 versus 95% CI: 0.84 to 1.12, and 95% CI: log(s) 1.18 to 1.43 versus 95% CI: 1.41 to 1.66, respectively. Both were comparable at later time points. Vision-related QOL (scale 0-100) did not differ significantly between both groups at any time point and improved significantly at 3 months (ß = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (ß = 5 [95% CI: 0 to 9]; p = 0.06). CONCLUSIONS: Descemet membrane endothelial keratoplasty (DMEK) results in lower posterior corneal HOAs compared with ultrathin DSAEK. Contrast sensitivity and straylight recover faster after DMEK but reach similar levels with both techniques at 1 year. Vision-related QOL improved significantly after surgery, but did not differ between both techniques.

Suppressive myeloid cells are a hallmark of severe COVID-19

Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46+n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DRhiCD11chi inflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DRto monocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.

Clinical significance of the serum to urinary thioredoxin ratio for diagnosis and prediction of the severe acute pyelonephritisin children / 中国医师进修杂志

investigate the diagnostic and predictable value of the levels of serum Trx (S-Trx), urinary Trx (U-Trx) and S-Trx/U-Trx ratio in acute pyelonephritis of children. Methods A total of 120 children with urinary tract infection were divided into APN group (67 cases) and non-APN group (53 cases).In addition , 67 children with APN were assigned to severe group (23 cases )and non-severe group (44 cases). The leves of serum C-reactive protein(CRP), precalcitonin(PCT), cystatin C (CysC), Trx (S-Trx) and urinary β2-microglobulin(β2-MG), neutrophill gelatinase-related apolipoprotein (NGAL), Trx (U-Trx) were collected. Besides, the ratio of S-Trx/U-Trx was also counted. The diagnostic and predictable value of each index were determined by receiver operating characteristic (ROC). Results Serum PCT, S-Trx, urinary β2-MG, NGAL, U-Trx was markedly increased and S-Trx/U-Trx ratio was obviously decreased in the APN group compared to that of the non-APN group (P＜0.05). Moreover, S-Trx, urinary NGAL, U-Trx was significantly increased and S-Trx/U-Trx ratio was significantly decreased in the severe group compared to that of the non-severe group (P＜0.05). Both in APN group or severe APN group, S-Trx and U-Trx displayed significantly positive correlation (P＜0.05). The results from ROC demonstrated that AUC were 0.960, and optimal cut-off value were 16.17 μg/L of U-Trx diagnostic APN in children, with a specificity and sensitivity of 94.34% and 92.54%, respectively. The optimal cut-off value was 1.29.AUC of S-Trx/U-Trx 0.960 predicted the severe of APN in children, with a specificity and sensitivity of 81.82% and 82.61%, respectively. Conclusions U-Trx is useful for diagnostic APN in children, S-Trx/U-Trx is an independent predictor of the severe APN.

Clinical significance of the serum to urinary thioredoxin ratio for diagnosis and prediction of the severe acute pyelonephritisin children / 中国医师进修杂志

Objective@#To investigate the diagnostic and predictable value of the levels of serum Trx (S-Trx), urinary Trx (U-Trx) and S-Trx/U-Trx ratio in acute pyelonephritis of children.@*Methods@#A total of 120 children with urinary tract infection were divided into APN group (67 cases) and non-APN group (53 cases).In addition, 67 children with APN were assigned to severe group (23 cases)and non-severe group (44 cases). The leves of serum C-reactive protein(CRP), precalcitonin(PCT), cystatin C (CysC), Trx (S-Trx) and urinary β2-microglobulin(β2-MG), neutrophill gelatinase-related apolipoprotein (NGAL), Trx (U-Trx) were collected. Besides, the ratio of S-Trx/U-Trx was also counted. The diagnostic and predictable value of each index were determined by receiver operating characteristic (ROC).@*Results@#Serum PCT, S-Trx, urinary β2-MG, NGAL, U-Trx was markedly increased and S-Trx/U-Trx ratio was obviously decreased in the APN group compared to that of the non-APN group (P<0.05). Moreover, S-Trx, urinary NGAL, U-Trx was significantly increased and S-Trx/U-Trx ratio was significantly decreased in the severe group compared to that of the non-severe group (P<0.05). Both in APN group or severe APN group, S-Trx and U-Trx displayed significantly positive correlation (P<0.05). The results from ROC demonstrated that AUC were 0.960, and optimal cut-off value were 16.17 μg/L of U-Trx diagnostic APN in children, with a specificity and sensitivity of 94.34% and 92.54%, respectively. The optimal cut-off value was 1.29.AUC of S-Trx/U-Trx 0.960 predicted the severe of APN in children, with a specificity and sensitivity of 81.82% and 82.61%, respectively.@*Conclusions@#U-Trx is useful for diagnostic APN in children, S-Trx/U-Trx is an independent predictor of the severe APN.

Evaluation of right ventricular systolic function and effects of maintenance hemodialysis on it in uremic patients by 4D RV Volume / 中华超声影像学杂志

To evaluate the right ventricular systolic function in uremia patients and the effects of maintenance hemodialysis on right ventricular systolic function by volume and strain parameters obtained by 4D RV Volume . Methods Seventy‐six patients with uremia and twenty‐two controls were selected . According to left ventricular ejection fraction ( LVEF) ,uremia patients were divided into normal LVEF uremia group and decreased LVEF uremia group . T hen normal LVEF uremia group was divided into maintenance hemodialysis group and non‐dialysis group . Conventional ultrasound parameters included :LVEF ,pulmonary artery systolic pressure ( PASP) and tricuspid annular plane systolic excursion ( T APSE‐2D) . 4D RV Volume parameters included : right ventricular end‐diastolic volume ( RVEDV ) , tricuspid annular plane systolic excursion ( T APSE‐4D ) ,right ventricular area change rate ( FAC ) ,right ventricular ejection fraction ( RVEF) and right ventricular free wall longitudinal systolic strain ( RV‐GLSfree ) . Results①Compared with the control group ,T APSE‐2D decreased significantly in the decreased LVEF uremia group ( P ＜0 .05) ,w hile there was no significant difference of T APSE‐2D in normal LVEF uremia group ( P ＞ 0 .05) . Compared with the control group and normal LVEF uremia group ,PASP increased significantly in the decreased LVEF uremia group ( P ＜ 0 .05 ) . Compared with the control group ,RVEDV increased significantly both in the normal LVEF and decreased LVEF uremia group ,w hich showed an increasing trend in these three groups ( P ＜0 .05) ,while T APSE‐4D ,FAC ,RVEF and RV‐GLSfree all decreased significantly and showed a decreasing trend in these three groups ( P ＜ 0 .05 ) . ② Compared with the control group , T APSE‐2D decreased significantly in non‐dialysis group ( P ＜0 .05) ,but there was no significant difference in uremia hemodialysis group ( P ＞0 .05) . Compared with the control group ,PASP and RVEDV increased and T APSE‐4D ,FAC ,RVEF and RV‐GLSfree decreased significantly in uremia hemodialysis group and non‐dialysis group ( P ＜ 0 .05 ) . Compared with non‐dialysis group , T APSE‐2D and T APSE‐4D increased significantly in hemodialysis group ( P ＜0 .05) ,while there was no significant difference in RVEDV ,FAC , RVEF and RV‐GLSfree in uremia hemodialysis group ( P ＞0 .05) . Conclusions 4D RV Volume could early and accurately evaluate the right ventricular systolic dysfunction in uremia patients . Furthermore ,w hen evaluating right ventricular systolic function in uremia patients treated with maintenance hemodialysis , indices such as right ventricular strain and volume parameters should be comprehensively considered .

A preliminary study for the feasibility and accuracy of three-dimensional printing mitral annulus models based on echocardiographic data / 中华超声影像学杂志

Objective To evaluate the feasibility of three-dimensional (3D) printing of mitral annulus with transesophageal echocardiographic volume images as the data source ,and to assess the accuracy of the 3D printing mitral annulus models based on three dimensional transesophageal echocardiography ( 3D-TEE) images preliminarily . Methods A retrospective study was performed in 25 patients with mild or slight mitral regurgitation and 10 patients with moderate to severe mitral regurgitation . All the subjects were underwent 3D-TEE . The 3D-TEE volume images of mitral annulus at the end diastole were post-processed by Mimics software to create images of the mitral annulus in standard tessellation language format . The STL file was output to the 3D printer and the 3D printing models of mitral annulus were obtained . The mitral annulus size parameters including the diameter between anterior and posterior ,the diameter between anterolaterior and posteromedial ,sphericity index and mitral annulus circumference were measured from 3D printing models and 3D-TEE images ,respectively . From which the absolute difference of the measurements between 3D printing models and the 3D-TEE images were calculated . Results All of the 3D-TEE images were successfully post-processed ,and the corresponding 3D printing models were acquired by high-precision 3D printer . It showed no significant difference in all the mitral annulus size parameters between 3D printing modelsand3D-TEEimages(allP >0.05) .Morever,thesizeparameterswereconcordantwellbetweenthe two methods ,all of the data points fell within the limits of agreement . It showed little absolute difference in value of the mitral annulus size parameters between the 3D printing mitral annulus models and the 3D-TEE images . Conclusions It is technically feasible to print 3D models of mitral annulus using 3D-TEE images as the data source . 3D printing mitral annulus models based on transesophageal echocardiographic volume images have high precision .

Assessment of left ventricular diastolic function in patients with uremia by diastolic strain rate parameters / 中华超声影像学杂志

Objective To evaluate the left ventricular diastolic function in patients with uremia by two-dimensional speckle tracking technology ( 2D-STI ) . Methods Ninety-three patients with uremia ( serum creatinine value≥ 700 μmol/l) and 29 controls were included . Uremia patients were divided into group with decreased LVEF ( LVEF < 50％ ,group C ,19 cases) and group with normal LVEF ( LVEF≥50％ ) . The latter were divided into group with normal diastolic function ( group A ,31 cases) and group with diastolic dysfunction ( group B ,23 cases) according to the diastolic function;pulsed wave tissue Dopper imaging datas included:diastolic velocity e1′,a1′ and e2′,a2′ at septal or lateral sites of mitral annulus , average E/e′and e′/a′. 2D-STI strain and strain rate parameters included:the longitudinal peak systolic strain ( GLS) ,the longitudinal peak systolic strain rate ( LSRs) ,longitudinal peak strain rate in early diastole (LSRe)andE/LSRe.Results ①Systolicfunctionparameters:comparedwithcontrolgroup,LVEF decreased significantly only in group C( P <0 .05) ,while there was no significant difference among group A ,B and control group ( P> 0 .05 ) ;GLS in group A ,B and C decreased significantly and showed a decreasing trend among these three groups( P <0 .05) ;LSRs in group B and C decreased significantly ,while there was no significant difference between group A and control group( P > 0 .05) . ② Diastolic function parameters:compared with control group ,the average E/e′decreased significantly in group B and C( P <0 .05) ,while group A showed no significant difference( P > 0 .05) . Compared with group A ,the average E/e′increased significantly in group B and C ( P < 0 .05) . Compared with control group ,LSRe in three uremia groups decreased significantly ,which showed a decreasing trend among these three groups ( P <0 .05) ;however ,E/LSRe in three uremia groups increased significantly and showed an increasing trend among these three groups ( P < 0 .05 ) . ③ The correlation analysis showed that there were positive correlations between average e′ and LSRe and between average E/e′ and E/LSRe in uremic patients . Conclusions In patients with uremia ,left ventricular systolic and diastolic function impaired in the early phase . Strain rate parameters in diastole especially E/LSRe obtained by 2D-STI can be used as sensitive , early parameter for evaluation of left ventricular diastolic dysfunction .

Comparative study of 3D reconstruction of left atrial appendage model based on ultrasound and CT 3D DICOM data / 中华超声影像学杂志

Objective To investigate the consistency of the anatomical parameters of left atrial appendage (LAA) based on three-dimensional transesophageal echocardiography (3D-TEE) and CT of 3D print datasource by the post-processing of DICOM data.Methods Sixty-three patients with atrial fibrillation in our hospital who underwent 3D-TEE and cardiac CT examination were selected and the original DICOM data of the LAA were obtained.The volume images of LAA were acquired by the postprocessing of Mimics software.After measuring and evaluating the anatomical parameters,the differences of parameters between TEE and CT were compared and the consistency of the two methods was evaluated.Results The data of 63 patients with atrial fibrillation obtained by 3D-TEE and CT were successfully post-treated and the detailed anatomical parameters of LAA were obtained.Morphological parameters:the Kappa values of the anatomical shape and opening shape of the LAA based on the 3D-TEE and CT data were 91.0%,69.3%,respectively.Measurement parameters:the area,perimeter,long axis,short axis of ostiums of LAA,and depth of LAA by CT were larger than those by 3D-TEE(all P0.05).LAA′measurements of 3D-TEE was concordant well with CT′s by Bland-Altman analysis.Conclusions In agreement with CT,3D-TEE can also be used as a datasource for 3D printing by evaluating spatial morphology of the LAA.

Assessment of left ventricular dyssynchrony and its relationship with cardiac function in dilated cardiomyopathy by two-dimensional strain parameters / 中国医学影像技术

Objective To explore value of two-dimensional speckle tracking imaging (2D-STI) strain parameters in assessment of left ventricular (LV) dyssynchrony and its relationship with cardiac function in patients with dilated cardiomyopathy (DCM).Methods Totally 25 patients with DCM and 25 age-matched normal controls were enrolled.The LV time to peak longitudinal strain (Tls) and time to peak circumferential strain (Tcs) were measured by 2D-STI,from which the standard deviations and maximal differences of the Tls in all 18 segments,6 segments at apical 4-chamber,3-chamber and 2 chamber views (Tls-SD,Tls-SD-4,Tls-SD-3,Tls SD-2,Tls dif,Tls-dif-4,Tls-dif-3,Tls-dif-2) were calculated,as same as the standard deviations and maximal differences of Tcs in all 18 segments,6 segments at mitral valve,papillary muscle,apical short-axis views (Tcs-SD,Tcs-SD-M,Tcs-SD-P,Tcs-SD-A,Tcs-dif,Tcs-dif-M,Tcs-dif-P,Tcs-dif-A) were calculated.Results Compared with the control group,the global and segmental strain parameters of the DCM group increased significantly (all P＜0.05).Except for Tcs-dif-P and Tcs dif,the residual strain parameters were negatively correlated with LV ejection fraction (all P＜0.05).Except for Tcs-dif-M,Tcs dif-P and Tcs-dif,there was a positive correlation between strain parameters and E/e in DCM group (all P ＜0.05).Conclusion In patients with DCM,LV dyssynchrony exists both in global and regional,which may aggravates the LV function damage.2D-STI strain parameters can objectively evaluate LV dyssynchrony and its relationship with cardiac function in patients with DCM.

The accuracy of ultrasound-derived three-dimensional printing models for atrial septal defect / 中华超声影像学杂志

Objective To evaluate the accuracy of three-dimensional printing atrial septal defect (ASD)models from three dimensional transesophageal echocardiography(3D-TEE)images and to lay the foundation for the application of 3D printing technology in the diagnosis and treatment of ASD.Methods Twenty patients with ASD were analyzed retrospectively.2D-TEE and 3D-TEE were performed before ASD occlusion.The 3D-TEE data were post-processed by Mimics software and the volume images of ASD in STL format were developed.Then the STL file was output and the ASD 3D models were printed.The ASD size parameters included the maximal diameter(Dmax),the minimal diameter(Dmin),circumference(C)and area(A),which were measured from 2D-TEE images,3D-TEE images and 3D printing models,respectively. The absolute difference value of ASD size parameters between 3D printing models and 2D-TEE images,or 3D-TEE images were calculated.The sizes of occluder were recorded during the operation and the preoperative exercises on 3D printing models were performed.Results There were no significant difference in ASD size parameters among 3D printing models,2D-TEE and 3D-TEE images(all P > 0.05),the ASD size parameters were concordant well between 3D printing models and 2D-TEE or 3D-TEE images. Moreover,the absolute difference value of ASD size parameters between 3D printing models and 2D-TEE or 3D-TEE images were little.In addition,linear regression analysis revealed a significant correlation in the Dmaxmeasured from 3D printing models and the sizes of occulder used in the operation(r =0.94,P <0.05).In the ASD 3D printing models the preoperative exercise had an impressive effect.Conclusions It is quite feasible to use 3D-TEE images as the data source of ASD 3D printing models.Ultrasound-derived ASD 3D printing models are of highly accuracy,which have the potential to provide evidence for the clinical application of 3D printing technology.

Hyperthermic intraperitoneal chemotherapy plus high-frequency diathermic therapy followed by intravenous chemotherapy versus intravenous chemotherapy alone for postoperative adjuvant treatment of gastrointestinal cancer: a comparative research study.

PURPOSE: To evaluate the therapeutic efficacy and toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) plus high-frequency diathermic therapy (HFDT) followed by intravenous chemotherapy vs intravenous chemotherapy alone for adjuvant treatment of postoperative gastrointestinal neoplasms. METHODS: Fifty-two gastrointestinal carcinoma patients who were radically operated were enrolled and divided into the treatment group and the control group. In the treatment group, 25 patients were treated with combination of HIPEC+HFDT and subsequent intravenous chemotherapy, while in the control group 27 patients received intravenous chemotherapy alone. Post-therapeutic complications and adverse reactions, time to progression (TTP) and overall survival (OS) were compared between these two groups. RESULTS: Difference in toxic reactions between the two groups was not statistically significant (p>0.05). Postoperative progression- free survival (PFS) rate at 12 and 40 months after radical surgery was 72.0 and 54.0% respectively in the treatment group, and 65.8 and 11.5% respectively in the control group (p=0.108). TTP was statistically significantly longer in the treatment group than in the control group (median TTP 40.1 vs 18.5 months, p=0.027). Postoperative OS at 12 and 20 months after radical surgery was 88.0 and 78.0% respectively in the treatment group and 92.6 and 72.7% in the control group, without significant difference. CONCLUSION: After radical surgery, combination of HIPEC+HFDT and subsequent intravenous chemotherapy brings about superior PFS compared with intravenous adjuvant chemotherapy alone, while having no more complications and adverse reactions.

Correlation between bone marrow dose volumes and acute hematological toxicity in postoperative gynecological cancer patients.

OBJECTIVE: To identify the association between radiation dose volume and acute hematological toxicity (HT) in postoperative gynecological cancer patients receiving whole pelvic radiotherapy (RT) or intensity-modulated RT (IMRT), a principal component regression model was used to calculate HT. METHODS: Women (n=100) receiving with or without chemotherapy RT were retrospectively analyzed, 52 of whom received chemotherapy (paclitaxel and nedaplatin). The pelvis and lumbar vertebrae, defined as the prolong-pelvic bone marrow, were divided into the (1) combined ilium, ischium and pubis and the (2) lumbar vertebrae and the sacrum. The V5-V40 of subsides was calculated. The complete blood counts were recorded weekly. The principal component analysis was performed on volumes which generated the principal components (PCs), followed by using a logistic regression model. RESULTS: Forty-seven patients presented with grade 2-3 HT during RT. Chemotherapy increased the incidence of HT compared with RT alone (70.21% vs. 29.79%; p=0.001). Fifty-three patients with persistent HT developed more serious HT at an earlier stage of RT. The chemotherapy cycles and three PCs associated with grade 2-3 HT was identified to form the resulting principal logistic regression model. CONCLUSION: A new method to calculate the NTCP was achieved by PCs logistic regression.

EGFR mutations and HER2/3 protein expression and clinical outcome in Chinese advanced non-small cell lung cancer patients treated with gefitinib.

BACKGROUND: To assess the role of various epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression as predictive markers of responsiveness to gefitinib therapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 106 Chinese NSCLC patients who had failed at least one chemotherapy regimen received gefitinib 250 mg once daily. All the 106 tumors from these patients were screened for mutations in the EGFR exons 18-24, and 84 tumors were studied by immunohistochemistry for HER2/3 expression and correlated with clinical treatment outcome. RESULTS: Patients with EGFR mutations had a significantly higher overall response rate (ORR), longer time to progression (TTP) and overall survival (OS) compared with those with wild-type receptor. No difference in ORR was observed between patients with exon 19 deletion and patients with other EGFR mutations. ORR in HER2-positive patients was significantly higher than in the HER2-negative group, irrespective of EGFR mutational status, and a trend for better ORR was observed for HER3-positive patients. HER2 and HER3 expression levels were not associated with any difference in terms of TTP and OS. Nevertheless, when considering the subgroups of non-responders to gefitinib, median TTP in patients with mutated EGFR was significantly longer than in those with no mutations (8.0 vs. 3.0 months, P = 0.0065). EGFR-mutated patients had no significant difference in ORR, TTP and OS according to HER2 and/or HER3 expression. CONCLUSIONS: EGFR mutations are effective predictors for gefitinib efficacy in Chinese patients with advanced NSCLC. HER2 and HER3 expression does not provide any additional information for selecting patients most likely to benefit from gefitinib treatment.

Adaptation of humoral memory.

Immunological memory, as provided by antibodies, depends on the continued presence of antibody-secreting cells, such as long-lived plasma cells of the bone marrow. Survival niches for these memory plasma cells are limited in number. In an established immune system, acquisition of new plasma cells, generated in response to recent pathogenic challenges, requires elimination of old memory plasma cells. Here, we review the adaptation of plasma cell memory to new pathogens. This adaptation is dependent upon the influx of plasmablasts, generated in a secondary systemic immune reaction, into the pool of memory plasma cells, the efficiency of competition of new plasmablasts with old plasma cells, and the frequency of infection with novel pathogens. To maintain old plasma cells at frequencies high enough to provide protection and to accommodate as many specificities as possible, an optimal influx rate per infection exists. This optimal rate is approximately three times higher than the minimal number of plasma cells providing protection. Influx rates of plasmablasts generated by vaccination approximately match this optimum level. Furthermore, the observed stability of serum concentrations of vaccine-specific antibodies implies that the influxing plasmablasts mobilize a similar number of plasma cells and that competitive infectious challenges are not more frequent than once per month.