Risk of disease recurrence and survival in patients with multiple myeloma: A German Study Group analysis using a conditional survival approach with long-term follow-up of 815 patients.

BACKGROUND: Unlike the traditional method of overall survival prediction in patients with cancer, conditional survival predicts the survival of patients dynamically throughout the course of disease, identifying how a prognosis evolves over time. METHODS: The authors assessed 815 consecutive patients with multiple myeloma through the German Study Group on Multiple Myeloma (Deutsche Studiengruppe Multiples Myelom; DSMM) incentive. Over 10 variables, including patient-specific and multiple myeloma-specific parameters, were analyzed at the time of initial diagnosis and repeatedly during follow-up. The probability of survival for another 5 years was calculated according to disease-related and host-related risks. Multivariate Cox models were used to determine baseline and updated prognostic factors for survival. RESULTS: The median follow-up and overall survival were 10.3 years and 5.1 years, respectively. When comparing 5-year conditional survival probabilities from the data derived at the time of initial diagnosis with those updated over time, substantially differing prognoses were observed when follow-up data were used. Multivariate Cox regression models for cohorts surviving 0 to 5 years demonstrated hazard ratios (HRs) for patients aged <60 years, 60 to 69 years, and >70 years of 1, 1.68, and 3.17, respectively. These HRs for age were found to decline for patients surviving 5 years, as well as for those with advanced stages of disease (II/III) and unfavorable cytogenetics, whereas progressive disease remained an important factor in patients surviving 1 year, 3 years, and 5 years, with HRs of 1.85, 2.11, and 2.14, respectively. CONCLUSIONS: To the authors' knowledge, the current study is the first analysis of conditional survival in patients with multiple myeloma using both baseline and follow-up risk parameters, demonstrating that regular risk assessment throughout the course of disease and complete follow-up provide a more reliable conditional survival estimation than baseline assessment alone.

Effectiveness of Couple Therapy in Practice Settings and Identification of Potential Predictors for Different Outcomes: Results of a German Nationwide Naturalistic Study.

Even though couple therapy is efficacious, there is no improvement in up to 50% of the couples. Also effect sizes found in effectiveness studies in real-world settings are considerably lower than those found in efficacy studies. There is a need to understand more about couple therapy effectiveness in practice settings and the factors responsible for different outcomes. A German nationwide study on the effectiveness of couple counseling including 554 couples applied the same methodology as two earlier studies in the same field. A remarkable consistency was found over the three independent studies in the burden with individual and relationship distress as well as in the rates of improvement. This supports the insight that the improvements reached through couple therapy in practice settings are only about half of the effect sizes reached in efficacy trials. Additionally this study investigated 64 factors, which were found to be influential for relationship quality and stability in earlier studies, for their impact on outcome. Factors present at initiation and termination of therapy were found, which correlate significantly with outcome and with separation of the couple in the follow-up. These factors could be included in prediction models for improvement and separation of the couple. The implications for the practice of couple therapy and for future research are discussed.

Aunque la terapia de pareja es eficaz, no se producen mejoras en hasta el 50 % de las parejas. Además, los tamaños del efecto hallados en los estudios de eficacia real en entornos del mundo real son considerablemente menores que los hallados en los estudios de eficacia teórica. Existe la necesidad de saber más acerca de la eficacia real de la terapia de pareja en la práctica clínica y de los factores responsables de los diferentes resultados. Un estudio alemán a nivel nacional sobre la eficacia real de la terapia de pareja en el que participaron 554 parejas aplicó la misma metodología que dos estudios anteriores en el mismo ámbito. Se halló una coherencia notable entre los tres estudios independientes en la carga con el distrés individual y relacional, así como en los índices de mejora. Esto respalda la percepción de que las mejoras logradas mediante la terapia de pareja en la práctica clínica es solo aproximadamente la mitad de los tamaños del efecto logrados en ensayos de eficacia teórica. Además, este estudio investigó 64 factores que demostraron ser influyentes para la calidad y la estabilidad de la relación en estudios anteriores, por su efecto en los resultados. Se descubrieron factores presentes en el inicio y el final de la terapia que se correlacionan considerablemente con los resultados y con la separación de la pareja en el seguimiento. Estos factores podrían incluirse en modelos de predicción sobre la mejora y la separación de la pareja. Se debaten las implicancias para la terapia de pareja y para futuras investigaciones.

Creeping Fat Assessed by Small Bowel MRI Is Linked to Bowel Damage and Abdominal Surgery in Crohn's Disease.

BACKGROUND: Crohn's disease (CD) leads to bowel damage and surgery in a significant proportion of patients. AIMS: The aim of the study was to evaluate the predictive value of creeping fat assessed by small bowel MRI in CD patients. METHODS: CD patients undergoing small bowel MRI were included in a retrospective observational cohort study. Clinical findings were extracted and correlated with radiological outcome measures. Logistic regression analysis was performed to assess predictors associated with a complicated course and surgery within 2 years and long-term follow-up. RESULTS: Ninety patients (49% female, median follow-up 93 months) were included. Creeping fat was identified in 21.1%. Of these patients, 68% and 79% developed bowel damage (p < .05) and 42% and 63% of patients revealing creeping fat underwent surgery within 2 years following MRI and total follow-up, respectively. The presence of creeping fat [odds ratio (OR) 4.0], inflammatory stenosis (OR 3.7), multisegmental (small) bowel (OR 4.5 and 3.8), and proximal small bowel inflammation (OR 5.0) were associated with inferior outcome (p < .05) in a univariate analysis. Creeping fat was independently associated with a disabling course, bowel damage, and surgery (OR 3.5 each, p < .05) in a multivariate analysis model. CONCLUSION: Creeping fat identified by small bowel MRI is associated with a complicated course and abdominal surgery in CD. Our data adds evidence that small bowel MRI facilitates risk stratification in order to define a patient at risk of disease-related complications in CD. [DRKS00011727, www.germanctr.de/ ].

Extravasation of contrast (Spot Sign) predicts in-hospital mortality in ruptured arteriovenous malformation.

BACKGROUND AND PURPOSE: The spot sign is a highly specific and sensitive predictor of hematoma expansion in following primary intracerebral hemorrhage (ICH). Rare cases of the spot sign have been documented in patients with intracranial hemorrhage secondary to arteriovenous malformation (AVM). The purpose of this retrospective study is to assess the accuracy of spot sign in predicting clinical outcomes in patients with ruptured AVM. MATERIALS AND METHODS: A retrospective analysis of a prospectively maintained database was performed for patients who presented to West China Hospital with ICH secondary to AVM in the period between January 2009 and September 2016. Two radiologists blinded to the clinical data independently assessed the imaging data, including the presence of spot sign. Statistical analysis using univariate testing, multivariate logistic regression testing, and receiver operating characteristic curve (AUC) analysis was performed. RESULTS: A total of 116 patients were included. Overall, 18.9% (22/116) of subjects had at least 1 spot sign detected by CT angiography, 7% (8/116) died in hospital, and 27% (31/116) of the patients had a poor outcome after 90 days. The spot sign had a sensitivity of 62.5% and specificity of 84.3% for predicting in-hospital mortality (p = .02, AUC 0.734). No correlation detected between the spot sign and 90-day outcomes under multiple logistic regression (p = .19). CONCLUSIONS: The spot sign is an independent predictor for in-hospital mortality. The presence of spot sign did not correlate with the 90 day outcomes in this patient cohort. The results of this report suggest that patients with ruptured AVM with demonstrated the spot sign on imaging must receive aggressive treatment early on due to the high risk of mortality.

The impact of route of diagnosis on survival in patients with glioblastoma.

INTRODUCTION: The standard of care for glioblastoma is maximal debulking surgery followed by chemo-radiotherapy (CRT). Published data show worse outcomes for patients who present with GBM as an emergency. This study investigates prognostic factors in a cohort of GBM patients treated with postoperative CRT, and compares outcomes in patients who present via emergency pathways with those who present through outpatient clinics. METHODS: Patients with GBM operated on between 1 April 2010 and 5 October 2015 and then treated with postoperative CRT were included in the study. Data were collected from electronic patient records and radiotherapy planning systems. Survival data were censored on 22 March 2016. Univariate and multivariate analyses of prognostic factors were performed. RESULTS: 104 patients were studied; mean age 51.6 years (range 19 to 70 years). Median overall survival (OS) was 16.5 months, with 68.2% and 37.8% alive at 12 and 24 months respectively. On multivariate analysis, improved OS was associated with ECOG Performance Status of 0 (vs ≥1; p = .012), patient age <60 years (vs ≥60 years; p < .001), and surgical debulking or macroscopic complete resection (vs biopsy; p < .001). Patients who presented through emergency medical pathways had worse survival (p = .005). CONCLUSION: This study supports published data that initial presentation through emergency pathways is associated with worse outcomes in GBM, even in patients who remain fit enough to receive post-operative CRT.

Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection. DESIGN: Patients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread. DISCUSSION: Pancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy. Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00006179 .

Current UK practice of pre-operative risk assessment prior to neurosurgery.

BACKGROUND: Intra-cranial and spinal surgery is associated with significant morbidity (23.6% and 11.2%) (5) . Fully informed consent, shared decision-making and optimal peri-operative care are essential to ensure excellent surgical outcome. There is evidence to support the use of formal pre-operative risk assessment to facilitate this in non-cardiac surgery but little is published on best practice for neurosurgery. Our aim was to establish current practice in pre-operative risk assessment at UK Neurosciences centres. METHODS: A national peer-reviewed electronic structured survey on current practice of pre-operative risk assessment was conducted through the Neuroanaesthesia Society of Great Britain and Ireland or NASGBI in 2014. RESULTS: We received a response from every UK neurosciences centre. 85% of neurosurgical units offer pre-operative assessment or PAC for elective admissions with 32% of respondents performing formal risk assessment. The Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) and its Portsmouth (P-POSSUM) modification were used most frequently. Although formal multi-disciplinary team discussions were conducted rarely following risk assessment, the results guided post-operative care and were used for consent. CONCLUSIONS: Our survey is the first of its kind in the UK for neurosciences. As expected, formal risk assessment and multi-disciplinary team discussion is not routine. Neurosurgery has a high risk of morbidity and mortality, and pre-operative risk assessment should therefore be considered in line with national recommendations. Further work is required to establish best practice in neurosurgery to ensure that patients are appropriately consented, and to improve standards of care and support surgical outcome data.

Correlation between pedicle size and the rate of pedicle screw misplacement in the treatment of thoracic fractures: Can we predict how difficult the task will be?

STUDY DESIGN: A retrospective study. OBJECTIVE: To correlate the incidence of pedicle-screw (PS) misplacement with the dimensions of the pedicles in the treatment of thoracic spine fractures. SUMMARY OF BACKGROUND DATA: The technical challenge of internal fixation with PS in the thoracic spine has been well documented in the literature. However, there are no publications that document the correlation between the pedicle dimensions of the thoracic vertebrae in the preoperative computed tomography scans (CT) and the rate of PS misplacement. METHODS: All patients who had PSs inserted between the T1 and T12 vertebrae during a 24-month period were included in this study. PS position was assessed on high quality CT scans by two independent observers and classified in 2 categories: correct or misplaced. The transverse diameter, craniocaudal diameter and cross-sectional area of the pedicles from T1 to T12 were measured in the pre-operative CT. RESULTS: During the period of this study 36 patients underwent internal fixation with 218 PS. Of the 218 screws, 184 (84.5%) were correct and 34 (15.5%) were misplaced. Misplacement rate was 33% for pedicles with a transverse diameter less than 5 mm, 10.7% for those with a transverse diameter between 5 and 7 mm and 0% for those with a transverse diameter larger than 7 mm. There was a statistically significant difference in the rate of PS misplacement in pedicles with transverse diameter smaller than 5 mm compared with the others. Also, those with transverse diameter between 5.1 and 7 mm compared with those bigger than 7 mm in diameter. The rate of PS misplacement was higher between T3 and T9 (p < 0.05), which in turn correlated with pedicle transverse diameter. CONCLUSION: The rate of PS misplacement in the mid thoracic spine (T4-T9) is high and correlates with pedicle transverse diameter.

When to hold and when to fold: Early prediction of nonresponse to transcranial magnetic stimulation in major depressive disorder.

BACKGROUND: Determining when to recommend a change in treatment regimen due to insufficient improvement is a common challenge in therapeutics. METHODS: In a sample of 7215 patients with major depressive disorder treated with transcranial magnetic stimulation (TMS) and with PHQ-9 scores before, during and after the course, 3 groups were identified based on number of acute course sessions: exactly 36 sessions (N = 3591), more than 36 sessions (N = 975), and less than 36 sessions (N = 2649). Two techniques were used to determine thresholds for percentage change in PHQ-9 scores at assessments after 10, 20, and 30 sessions that optimized prediction of endpoint response status: the Youden index and fixing the false positive rate at 10%. Positive and negative predictive values were calculated to assess the accuracy of identifying final nonresponders and responders, respectively. RESULTS: There was greater accuracy in predicting final response than nonresponse, especially in the groups that had at least 36 sessions. Substantial proportions of patients with low levels of early improvement were classified as responders at the end of treatment. LIMITATIONS: The findings should be validated with clinician ratings using a more comprehensive depression severity scale. CONCLUSIONS: Manifesting clinical improvement early in the TMS course is strongly predictive of final status as a responder, while lack of early improvement is a relatively poor indicator of final nonresponse status. The predictive value of lack of early symptomatic improvement is too low to make reliable recommendations regarding changes in treatment regimen.

What is a Bladder Cancer Molecular Subtype? - Counterpoint.

In an accompanying paper, Mattias Höglund discusses on what is a bladder cancer molecular subtype. He emphasizes the need to consider the aim of tumor classification, which is obviously critical to the approach. He also focuses on considering primarily the identity features of the neoplastic cells. Here, we provide a counterpoint. While largely agreeing with his views, we underline that other parameters that may vary in a spatial or temporal scale, and the tumor microenvironment, can also provide relevant information to render tumor classifications clinically useful. Furthermore, tumor heterogeneity and evolution during the disease course - natural or under therapeutic pressure - should be considered.

Quantitative sonoelastography of the uterine cervix in predicting successful outcome of induction of labour.

Objectives: The aim of the study was to evaluate the stiffness of cervix and determine its significance in predicting successful outcome of induction of labour. The primary objective was to determine the differences in elastography indices of different areas of cervix between the outcome groups of successful and failed induction of labour. A secondary objective was to find out the correlation of these elastography indices with Bishop's score and cervical length. Methods: This was a prospective, observational study conducted over a period of 6 months on pregnant women admitted in the labour room for induction of labour. Establishment of adequate regular uterine contractions - at least three contractions lasting 40-45 s in a 10-min period - was taken as end point for successful outcome of induction of labour. Even after 24 h of initiation of induction of labour, regular, adequate and painful uterine contractions were not established, then induction of labour was described as having failed. Prior to induction, cervical length measurement, Bishop's scoring and elastographic evaluation of the cervix were done by stress-strain elastography. A colour map was produced from purple to red and a five-step scale - the elastography index - was used to describe the various parts of the cervix. The differences between elastography indices of different parts of cervix were estimated using Mann-Whitney U test. Correlation of the indices with cervical length and Bishop's score was determined by Spearman's correlation coefficient. Results: A total of 64 women were included in the study. A significant difference (p < 0.001) was found in the elastography index of internal os between the two outcome groups of success (1.76 ± 0.64) and failure (0.54 ± 0.18). However, the elastography index of central cervical canal, external os, anterior lip and posterior lips did not differ significantly across the outcome groups. A significant positive correlation was found between elastography index of internal os and cervical length (Spearman's correlation coefficient, r = 0.441, p < 0.001) and between elastography index of external os and cervical length (r = 0.347, p = 0.005), whereas a negative correlation was seen between elastography index of external os and Bishop's score (r = -0.270, p = 0.031). Conclusion: Elastography index of internal os can be used to predict outcome of induction of labour. Cervical elastography is a promising new technique for cervical consistency assessment. Further larger studies are required to determine some cut-off point for elastography index of internal os in prediction of outcome of induction of labour and to strongly establish the usefulness of cervical elastography for pregnancy management, preventing preterm delivery and establishment of cut-off points to determine successful induction.

Radiomic Analysis of Intrahepatic Cholangiocarcinoma: Non-Invasive Prediction of Pathology Data: A Multicenter Study to Develop a Clinical-Radiomic Model.

Standard imaging cannot assess the pathology details of intrahepatic cholangiocarcinoma (ICC). We investigated whether CT-based radiomics may improve the prediction of tumor characteristics. All consecutive patients undergoing liver resection for ICC (2009-2019) in six high-volume centers were evaluated for inclusion. On the preoperative CT, we segmented the ICC (Tumor-VOI, i.e., volume-of-interest) and a 5-mm parenchyma rim around the tumor (Margin-VOI). We considered two types of pathology data: tumor grading (G) and microvascular invasion (MVI). The predictive models were internally validated. Overall, 244 patients were analyzed: 82 (34%) had G3 tumors and 139 (57%) had MVI. For G3 prediction, the clinical model had an AUC = 0.69 and an Accuracy = 0.68 at internal cross-validation. The addition of radiomic features extracted from the portal phase of CT improved the model performance (Clinical data+Tumor-VOI: AUC = 0.73/Accuracy = 0.72; +Tumor-/Margin-VOI: AUC = 0.77/Accuracy = 0.77). Also for MVI prediction, the addition of portal phase radiomics improved the model performance (Clinical data: AUC = 0.75/Accuracy = 0.70; +Tumor-VOI: AUC = 0.82/Accuracy = 0.73; +Tumor-/Margin-VOI: AUC = 0.82/Accuracy = 0.75). The permutation tests confirmed that a combined clinical-radiomic model outperforms a purely clinical one (p < 0.05). The addition of the textural features extracted from the arterial phase had no impact. In conclusion, the radiomic features of the tumor and peritumoral tissue extracted from the portal phase of preoperative CT improve the prediction of ICC grading and MVI.

Prediction of Outcome After Endovascular Embolectomy in Anterior Circulation Stroke Using Biomarkers.

Stroke is a major public health problem that can cause a long-term disability or death due to brain damage. Serious stroke is frequently caused by a large vessel occlusion in the anterior circulation, which should be treated by endovascular embolectomy if possible. In this study, we investigated the use of the brain damage biomarkers tau, NFL, NSE, GFAp, and S100B to understand the progression of nervous tissue damage and their relationship to outcome in such stroke after endovascular treatment. Blood samples were taken from 90 patients pre-treatment and 2 h, 24 h, 48 h, 72 h and 3 months after endovascular treatment. Stroke-related neurological deficit was estimated using the National Institute of Health Stroke Scale (NIHSS) at admission and at 24 h. Neurological outcome was evaluated at 3 months. After stroke, tau, NFL, GFAp and S100B increased in a time dependent manner, while NSE remained constant over time. At 3 months, tau and GFAp levels were back to normal whereas NFL was still high. Tau, NFL and GFAp correlated well to outcome, as well as to infarct volume and NIHSS at 24 h. The best time for prediction of poor outcome was different for each biomarker. However, the combination of NIHSS at 24 h with either tau, NFL or GFAp at 48 h gave the best prediction. The use of biomarkers in the early setting after endovascular treatment of stroke will lead to a simplified and standardized way to estimate the nervous tissue damage and possibly complement the clinical judgement in foreseeing the need of rehabilitation measures.

The impact of isolated local recurrence on long-term outcome in early-breast cancer patients after breast-conserving therapy.

PURPOSE: To analyse the prognostic impact of isolated local recurrence (ILR) on long-term outcome for early-breast cancer patients treated with breast-conserving therapy. MATERIAL AND METHODS: The data of the EORTC 22881-10882 'boost-no boost' and 22922-10925 'IM-MS' trials were used to analyse the prevalence and outcome following ILR. A multistate model described the impact of intermediate events on long-term outcomes, taking into account various prognostic factors. This model was used to predict long-term outcomes after ILR. RESULTS: Of the 8367 patients included, 726 experienced an ILR, 11.6% of them within the first 2 years and 30.0% after 10 years. Ten-year cumulative breast cancer mortality rates after ILR were 58.2% in patients with an ILR within 2 years, 31.0% for ILR between 2 and 4 years, 17.6% in patients with an ILR between 4 and 10 years, and 29.7% for ILR after year 10 (p < 0.001). The multistate model showed that when tumour-free, younger breast cancer patients had a higher probability of developing ILR compared to older patients. Shorter time to ILR was associated with a higher chance to develop distant metastases (DM), and a shorter time to development of DM were associated with an increased hazard of breast cancer-related death. The multistate model enabled prediction of long-term outcome based on individual patient covariates, length of follow-up without recurrence and timing of ILR since randomisation. CONCLUSIONS: Outcome of early-breast cancer changed not only according to baseline risk factors but also according to the presence of intermediate events, time to these events, and subsequent follow-up without any further events.

EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19. METHODS: SARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions. RESULTS: EASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha. CONCLUSION: EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.

Prognostic value of initial bone marrow disease detection by multiparameter flow cytometry in children with neuroblastoma.

PURPOSE: Multicolor flow cytometry (MFC) is widely available, fast and has an easy-to perform approach for finding neuroblastoma (NB) cells among normal bone marrow (BM) hematopoietic cells. Aim of the study was to investigate prognostic significance of initial MFC tumor cells' detection in BM of children with NB. METHODS: 51 patients (24 boys and 27 girls) aged from 6 days to 15 years (median age 1 year 3 months) with NB were included in the study. BM samples at the time of diagnosis were obtained from 2 to 5 aspiration sites per patient. CD45(-)CD56(+)CD81(+)GD2(+)-cells were evaluated by MFC. RESULTS: NB cells were detected in BM by FC more frequently compared to conventional cytomorphology (49.0% and 29.4% patients, respectively, р = 0.043). Patients with NB cells detected in BM by MFC had significantly worse event-free survival and cumulative incidence of relapse/progression [0.24(0.08) and 0.60(0.10), respectively] compared to children with negative result of immunophenotyping [0.85(0.07) and 0.12(0.06), respectively, p < 0.001 in both cases]. BM involvement detection by MFC maintained its prognostic significance in various patients groups. In multivariate analysis, immunophenotyping proved to be an independent prognostic factor when analyzed jointly with other NB risk factors. In 42 patients BM involvement was also studied by RQ-PCR for PHOX2B and TH genes expression. Within groups of patients divided by RQ-PCR positivity, MFC-positivity retained prognostic significance. CONCLUSIONS: Thus flow cytometric BM involvement detection has very strong prognostic impact even stronger than RQ-PCR. It could be used in combination with other parameters for the treatment strategy choice in patients with NB.

Symptom Severity at Week 4 of Cognitive-Behavior Therapy Predicts Depression Remission.

Early response has been shown to predict psychotherapy outcome. We examined the strength of the relationship between early response and remission in 82 patients who received naturalistic cognitive-behavior therapy in a private practice setting, and 158 patients who received protocol cognitive therapy in a research setting. We predicted that the relationship between early response and remission would be substantial enough to guide clinical decision making in both samples, and that a simple model of severity at Week 4 of treatment would predict remission as effectively as a more complex change score. Logistic regressions showed that a simple model based on the Week 4 Beck Depression Inventory (BDI) score was as predictive of remission as more complex models of early change. A receiver operating characteristics analysis showed that BDI score at Week 4 was substantially predictive of remission in both the naturalistic and research protocol samples; the area under the curve was .80 and .84 in the naturalistic and protocol samples, respectively. To guide clinical decision making, we identified threshold scores on the BDI corresponding to various negative predictive values (probability of nonremission when nonremission is predicted). Our results indicate that depressed patients who remain severely depressed at Week 4 of cognitive therapy are unlikely to reach remission at the end of relatively brief (maximum 20 sessions) treatment. We discuss implications of our findings for clinical decision making and treatment development.

End-of-Treatment PET/Computed Tomography Response in Diffuse Large B-Cell Lymphoma.

"PET imaging with fluorodeoxyglucose (FDG), integrated with PET/computed tomography (FDG-PET/CT), is an effective management tool of diffuse large B-cell lymphoma (DLBCL). The results of end-of-treatment (EOT) FDG-PET/CT are more accurate for detection of active disease with residual masses on CT. Complete response defined by EOT FDG-PET/CT (PET-CR) correlates with long-term outcome of patients. Treatment efficacy is determined using EOT PET/CT rather than progression-free survival (PFS) for clinical trials assessing novel drugs. If the correlation of EOT PET/CT with PFS is further proven in large studies and meta-analyses, EOT PET-CR could serve as an expedited novel endpoint replacing PFS."

Does early response predict subsequent remission in bipolar depression treated with repeated sleep deprivation combined with light therapy and lithium?

BACKGROUND: The combination of three cycles of sleep deprivation (SD), light therapy (LT), and lithium has recently been proposed as a possible first-line treatment for bipolar depression. However, it is unclear whether early improvement predicts final response/remission in bipolar depression treated with this regimen. METHOD: We studied 220 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder. The relation between response to first SD and response/remission at the end of the treatment (day 6) was analyzed using logistic regression analysis. Severity of depression was rated using the Hamilton Depression Rating Scale (HDRS). Clinical response was defined as a ≥50% reduction in HDRS scores, and remission was defined as an HDRS score of ≤7. RESULTS: Among the 217 completers, 67.7% showed response and 54.4% reached remission at the end of the treatment. Multiple logistic regression analysis revealed that response after first recovery sleep (day 2) predicted final response and remission at the end of the treatment with high odds ratios (10.9 for response and 8.2 for remission); however, response immediately after the first SD (day 1) did not predict final response or remission. LIMITATIONS: Whether our results can be generalized to unipolar depression remains uncertain. CONCLUSION: Clinical status after first recovery sleep is a strong predictor of successful final outcome in patients with bipolar depression treated with the combination of repeated SD, LT, and lithium. Recovery sleep may play a role in inducing the antidepressant effect associated with the success of treatment.

Duration of untreated illness as a key to early intervention in schizophrenia: A review.

The first psychotic episode is classically viewed as a critical period which management is important in determining the long-term outcome of the schizophrenia (SCZ). For this reason, the duration of untreated illness (DUI), defined as the interval between the onset of the psychiatric disorder and the administration of the first pharmacological treatment, is a clinical variable that has been increasingly investigated due to its potentially modifiable nature and its value as a predictor of outcome. DUI is poorly applicable and highly unreliable in psychosis. The present critical review examines the impact of DUI and its more operative definition of "duration of untreated psychosis" (DUP) in the course and outcome of SCZ, focusing on its epidemiologic, clinical, prognostic factors. Length of DUP has been identified as positively related to a worst treatment response, symptom control and overall functional outcome in SCZ. Negative symptoms appear to be prominently related to longer DUP. Neuroimaging correlates of DUP have not been clearly outlined: few of the studies considering first-episode patients and DUP showed structural abnormalities. A low proportion of significant associations were found mostly in cerebellum and occipital lobe of patients with longer DUP. Also, evidence of an inverse correlation between cognitive alterations and DUP is not conclusive. DUI and DUP are multidimensional constructs that imply both intrinsic, illness related (e.g. subtle symptoms at onset) and extrinsic factors (e.g. access to mental health services), so that from its study sprouted in the last decades First-Episode Units, aimed at providing secondary prevention in SCZ such as providing a timely diagnosis and treatment to patients experiencing their first psychotic episode. Early intervention seems to ensure a shortened DUP, especially for people presenting with brief limited intermittent psychotic symptoms, and, ultimately, ensure a more favorable prognosis for patients affected by SCZ.