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Chronic lymphocytic leukemia (CLL) is the most common mature B-cell neoplasm in the West. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome. In this study, we explored the mutational profile of CLL patients expressing IGHV4-34 within different stereotypes and their association with prognostic factors and clinical outcome. A multi-institutional cohort of unselected 1444 CLL patients was analyzed by RT-PCR and bidirectional sequencing. Cytogenetics and molecular cytogenetics analyses were also performed. We identified 144 (10%) IGHV4-34 expressing cases, 119 mutated (M), 44 of them with stereotyped B-cell receptors. Subset #4 was the most frequent (56.8% of cases) followed by subsets #16 (13.6%), #29 (6.8%), and #201 (2.3%), with different distribution among countries. Analysis of somatic hypermutation profile showed significant differences among stereotyped subsets for G28>D/E, P45>S, E55>Q, and S64>I changes (p < 0.01) and high frequency of disruption of the glycosylation motif in the VH CDR2 region. All stereotyped IGHV4-34 cases showed normal karyotypes. Deletion 13q14 as a sole alteration was present in 42.8% of stereotyped cases with a different distribution among subsets. A shorter time to first treatment was found in non-stereotyped vs. stereotyped M-IGHV4-34 patients (p = 0.034). Our results add new information supporting the importance of recurrent amino acid changes at particular positions, contributing to refine the molecular characterization of South American CLL patients.

To determine in a group of patients with progressive metastatic neuroendocrine tumors (PM-NETs) treated with 177Lu-DOTATATE whether a correlation exists between somatostatin receptor (SSTR)-2 expression in various tumors on baseline 68Ga-DOTATATE PET and their response to therapy. A secondary aim was to determine whether an association exists between tumor product of diameter (POD) and PET-derived Krenning score.Patients treated PM-NETs who had SSTR-2 overexpression (SSTR-RADS 5) on screening 68Ga-DOTATATE PET and CT at baseline and 3 months after therapy completion were included. Marker lesions on baseline CT were reassessed on CT after therapy using adapted Southwest Oncology Group solid tumor evaluation criteria. For each lesion, bidimensional diameter on CT and SSTR expression on PET (SSTR-RADS uptake scorePET-derived Krenning score) were recorded. Logistic regression models fitted through generalized estimating equations were used to assess for an association between SSTR expression and response to therapy, or lesion's POD.Forty-one patients with SSTR-RADS 5 PM-NETs treated with 177Lu-DOTATATE were included. There were 135 marker lesions (mean 3.2 lesions/patient) with Krenning score of 4 (n = 74), 3 (n = 44) or 2 (n = 17). There was no association found between SSTR-2 expression, as determined by SSTR-RADS uptake score or PET-derived Krenning score, and POD or response to therapy.In patients with SSTR-RADS 5 PM-NETs treated with 177Lu-DOTATATE, there was similar response to therapy for all lesions with PET-generated Krenning score ≥2. No correlation was found between lesion's POD and level of tracer uptake.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI

Purpose: To describe the initial experience of an academic center using 18F-DCFPyL PET in managing men with recurrent prostate cancer. Materials &amp, Methods: This prospective, single-arm IRB-approved study included men with biochemical failure after primary therapy for prostate cancer and negative/equivocal CT and bone scintigraphy who were candidates for salvage therapy, as determined by a multidisciplinary panel of experts. 18F-DCFPyL PET was assessed for the presence and extent of recurrence: local, oligometastatic (≤4), or extensive. Post-PET management and clinical outcome, including PSA response, was documented. For patients who received PET-directed ablative therapies, response was categorized as “complete” if PSA became undetectable or “favorable” if PSA decreased ≥50%. Results: Forty-seven men with biochemical failure after radical prostatectomy (n = 29), primary radiotherapy (n = 15) or focal tumor ablation (n = 3) were included. PET was positive in (43/47) 91.5%, including local recurrence in (9/47) 19.2%, oligometastatic disease in (16/47) 34%, and extensive metastatic disease in (18/47) 38.3%. PET-directed focal ablative therapies without systemic therapy were given to (13/29) 44.8% of patients without extensive metastases on PET with a mean PSA response of 69% (median, 74.5%, range: 35–100). Favorable biochemical response was observed in (10/13) 76.9% of patients with limited recurrence on PET, and in 23.1% (3/13), there was complete response. Conclusion: 18F-DCFPyL PET was positive in &gt, 90% of patients with biochemical failure. For those with limited recurrence, PSMA PET-directed local ablative therapies resulted in favorable outcome in more than 3 in 4 patients, and in nearly a quarter of them, there was complete biochemical response.

To assess whether 18F-DCFPyL PET/multiparametric (mp)MR contributes to the diagnosis of clinically significant (cs) prostate cancer (PCa) compared to mpMR in patients with suspicion of PCa, or patients being considered for focal ablative therapies (FT). This ethics review board–approved, prospective study included 55 men with suspicion of PCa and negative systematic biopsies or clinically discordant low-risk PCa (n = 21) or those being considered for FT (n = 34) who received 18F-DCFPyL PET/mpMR. Each modality, PET, mpMR, and PET/MR (using the PROMISE classification), was assessed independently. All suspicious lesions underwent PET/MR-ultrasound fusion biopsies. There were 45/55 patients (81.8%) that had histologically proven PCa and 41/55 (74.5%) were diagnosed with csPCa. Overall, 61/114 lesions (53.5%) identified on any modality were malignant; 49/61 lesions (80.3%) were csPCa. On lesion-level analysis, for detection of csPCa, the sensitivity of PET was higher than that of mpMR and PET/MR (86% vs 67% and 69% [p = 0.027 and 0.041, respectively]), but at a lower specificity (32% vs 85% and 86%, respectively [p

PURPOSE: To determine whether quantitative PET parameters on baseline 68Ga-DOTATATE PET/CT (bPET) and interim PET (iPET) performed prior to second cycle of therapy are predictive of therapy response and progression free survival (PFS). PATIENTS & METHODS: Ninety-one patients with well-differentiated neuroendocrine tumors (mean Ki67, 8.3%) underwent 68Ga-DOTATATE PET/CT (DT- PET) to determine suitability for peptide receptor radionuclide therapy (PRRT) as part of a prospective multicenter study. Mean follow-up was 12.2 months. Of them, 36 patients had iPET. Tumor metrics evaluated: 1. Marker lesion-based measures: mean SUVmax and ratio to liver/spleen; 2. Segmented DT tumor volume (DTTV) measures: DTTV; SUVmax and SUVmean using liver and spleen as thresholds; 3. Heterogeneity parameters (coefficient of variance, kurtosis, and skewness). Wilcoxon rank sum test was used for association between continuous variables and therapy response as determined by clinical response. Univariable and multivariable Cox proportional hazards model were used for association with PFS. RESULTS: There were 71 responders and 20 non-responders. Using marker lesions, higher mean SUVmax and mean SUVmax(Tumor/Liver) were predictors of therapy response (P = 0.018 & 0.024, respectively). For DTTV, higher SUVmax and SUVmean using liver as threshold and lower kurtosis were predictors of favorable response (P = 0.025, 0.0055 & 0.031, respectively. These also correlated with longer PFS. iPET DTTV SUVmean using liver threshold and ratio iPET mean SUVmax using target lesions correlated with therapy response (P = 0.024 & 0.048, respectively) but not PFS. From the multivariable analysis adjusting for age, primary site and Ki67, mean SUVmax (P = 0.019), SUVmax T/L (P = 0.018), SUVmax T/S (P = 0.041), DTTV SUVmean Liver (P = 0.0052) and skewness (P = 0.048) remain significant predictors of PFS. CONCLUSION: Degree of somatostatin receptor expression and tumor heterogeneity as represented by several metrics in our analysis are predictive of therapy response and/or PFS. Change in these parameters after first cycle of PRRT did not correlate with clinical outcomes.

Our purpose was to determine the effect of a smoothing filter and partial-volume correction (PVC) on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on molecular imaging PSMA (miPSMA) scoring. Methods: Men who had biochemical recurrence of prostate cancer with negative findings on CT and bone scintigraphy were referred for 18F-DCFPyL (2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl) PET/CT. Examinations were performed on 1 of 2 different brands of PET/CT scanner. All suspected tumor sites were manually contoured on coregistered CT and PET images, and each was assigned an miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomic CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified rule-of-thumb (RoT) correction factor (CF) was derived for lesions at various sizes (

Purpose To determine the prognostic value of sarcopenia measurements done on staging [18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Methods Patients with early stage, surgically treated esophageal adenocarcinoma and available pre-treatment PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI 2/m2 in women and 2/m2 in men. Results Of the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, Lymphovascular Invasion (LVI) positive lymph nodes and sarcopenia were significant prognostic factors concerning RFS, and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS. Conclusion Combining the patients’ imaging derived sarcopenic status with standard clinical data, but not metabolic parameters offered an overall improved prognostic value concerning OS and RFS.

Background: Autoimmune encephalitis occurs as a subacute condition with a strong infectious association in children. In the last 20 years, the frequency of non-infectious cases has increased significantly Clinical case: A previously healthy eight-year-old male child with normal neurodevelopment, without a history of consanguinity, manifested progressive neurological deterioration with autoimmune encephalitis-limbic encephalitis up to hypothalamic dysfunction. Conclusion: In the mentioned case, it was documented that an inborn error of the immune system generated a severe neurological clinical picture, with permanent and irreversible damage, secondary to lack of immunological memory in the broad clinical context of a common variable immunodeficiency.

Aim: Investigate efficacy, safety and quality of life of Gammanorm®16.5% (subcutaneous immunoglobulin [SCIG]) in patients with primary immunodeficiencies (PIDs) and safety and to lesser extent efficacy in autoimmune diseases. Patients & methods: Medical records were extracted from 31 pediatric and 12 adult patients who received SCIG as part of the Personalized Program at University Children's Hospital, Bogotá, Colombia. Results: Mean SCIG dose was 28.7 g/month. Serious bacterial infections were observed in 7/33 patients in the PID group, most often bacterial pneumonia (3/33). There were no serious adverse events related to SCIG treatment. Drug-related adverse reactions were reported in 2/43 patients. Conclusion: Self-administration of SCIG provided effective protection, favorable tolerability and improved quality of life in patients with PIDs and autoimmune diseases from Colombia.

ResumenLa Enfermedad Granulomatosa Crónica, es una Inmunodeficiencia Primaria (IDP), clasificada dentro de los defectos funcionales de fagocitos, asociada a mutaciones en el complejo multiprotéico NADPH oxidasa, las cuales se asocian con el patrón de herencia de la enfermedad, siendo más frecuente los casos ligados al cromosoma X con una frecuencia del 60%, en donde es importante encontrar a las madres portadoras de la enfermedad. Las manifestaciones clínicas de esta enfermedad son infecciones recurrentes y severas generadas por bacterias catalasa positivas, además de levaduras. Los hallazgos clínicos más frecuentes son infecciones severas en piel, adenitis, hepatoesplenomegalia, neumonía recurrente, formación de granulomas y en aproximadamente un 40% de los pacientes BCGitis.El diagnóstico de la enfermedad granulomatosa crónica se ha realizado tradicionalmente con la técnica colorimétrica de nitro azul tetrazolium (NBT). Sin embargo, actualmente se dispone del ensayo de Dihidrorodamina 1,2,3 el cual se caracteriza por ser más sensible y específico además de permitir la detección del fenómeno de Lyonización en madres portadoras de la enfermedad como la actividad residual de la enzima.El objetivo de este estudio es describir el reporte de un caso clínico de EGC y la importancia del ensayo de Dihidrorodamina 1,2,3 por citometrìa de flujo, como apoyo en el diagnóstico de la EGC. Se trata de un estudio de reporte de caso, descriptivo, en el cual se realizó una búsqueda en la literatura científica, encontrando una correlación con los hallazgos clínicos y de laboratorio del paciente y su progenitora. Como resultado final del estudio, se observó una disminución severa en la producción de especies reactivas del oxígeno (EROs) en el paciente, además del fenómeno de Lyonización en su progenitora.Frente a la sospecha clínica de alteración funcional de fagocitos, la prueba de oxidación de Dihidrorodamina permite detectar la alteración en la producción especies reactivas del oxígeno (EROs) como el fenómeno de Lyonización.AbstractChronic granulomatous disease is a primary immunodeficiency (PID) classified within the phagocytes functional defects associated with mutations in the multi-protein enzyme complex, NADPH oxidase, which are associated with the pattern of inheritance of the disease. X-linked cases have a frequency of 60%, which makes it important to find surrogates of the disease. The clinical manifestations of this disease are recurrent, and with severe infections generated by catalase positive bacteria, as well as yeasts. The most common clinical findings are severe skin infections, lymphadenitis, hepatosplenomegaly, recurrent pneumonia, and granuloma formation in approximately 40% of patients with BCGitis.The diagnosis of chronic granulomatous disease has traditionally been made with the colorimetric nitro blue tetrazolium (NBT) technique. However, the currently available 1,2,3 dihydrorhodamine assay, which has shown to be more sensitive and specific, in addition to enable detection of the lyonisation phenomenon in mothers carrying the disease, as well as the residual activity of the enzyme.The aim of this study was to report a case of CGD, and the importance of 1,2,3 dihydrorhodamine test by flow cytometry, as support in its diagnosis. It is a descriptive study case report, and includes a search in the scientific literature, and finding a correlation with clinical and laboratory findings of the patient and the mother.The end result of the study, a severe decrease was observed in the production of reactive oxygen species (ROS) in the patient, in addition to the lyonisation phenomenon in the mother.Faced with clinical suspicion of functional impairment of phagocytes, the dihydrorhodamine oxidation test can detect the alteration in the production of reactive oxygen species (ROS) as well as the lyonisation phenomenon.

Introduction People with cancer are at increased risk of incidental venous thromboembolism (VTE) and PET-CT imaging is commonly used in this population. However, the prevalence of incidental VTE detected by PET-CT in patients with cancer and its impact on survival are unknown. Materials and Methods This retrospective study was approved by the local Institutional Review Board. 1331 consecutive adult patients with cancer who underwent PET-CT examination between 2009 and 2012 were included in the study (mean age: 57 ± 15 years). PET-CT reports were reviewed to identify patients with incidental VTE at the time of examination. Survival rates were assessed with Kaplan-Meier curves. The Cox proportional hazards model was used to determine the association between incidental VTE and overall survival, after controlling for clinical variables. Results Incidental VTE was detected in 19 patients (1.4%). Patients with genitourinary malignancies, colorectal cancer and lung cancer had the highest rates of incidental VTE at PET-CT. At multivariate analysis, incidental VTE detected by PET-CT was associated with worse overall survival independently of patient age, hospitalization status at time of PET-CT examination, and the presence of metastatic disease (Hazard ratio = 2.03; 95% confidence interval = 1.08-3.81, p = 0.028). Conclusion Incidental VTE was detected in 1.4% of adult patients with cancer undergoing PET-CT imaging. Diagnosis of incidental VTE at PET-CT imaging was associated with worse overall survival in this population.

Systemic treatment for cancer including chemotherapy or biologic agents can cause different changes in the skin or mucous membranes. These changes may represent a known adverse reaction to these drugs, although other etiologies should be considered. One of these, radiation recall dermatitis, is a rare and unpredictable phenomenon. Herein, we report two cases of this condition in women with metastatic breast cancer secondary to gemcitabine and the combination of capecitabine and ixabepilone.

International audience; Background : Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients.Objective : Our objective was to assess the effect of mycobacterial disease in patients with CGD.Methods : We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria.Results : Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients.Conclusion : Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.

Se presenta un caso clínico de paciente con linfoma no Hodgkin tratado; en control tomográfico habitual se le solicitó PET-CT para complementar su estudio, que demuestra un foco metabólicamente activo en el espesor de músculo aductor izquierdo sin traducción tomográfica evidente. La lesión fue estudiada con ultrasonografia de partes blandas y biopsia dirigida, que resultó positiva para infiltración secundaria por linfoma. Este caso demuestra la utilidad de las técnicas complementarias en el manejo de estos pacientes, en especial la utilidad del PET-CT en el estudio de sitios inhabituales de diseminación. En este examen existe la posibilidad de identificar con precisión la localización de las lesiones mediante la TC complementaria, lo que permite efectuar posteriormente el estudio dirigido.

The audibility of patient clinical alarms to nursing personnel was tested during the first shift on a medical/surgical in-patient ward at William Beaumont Army Medical Center. This study was conducted during normal hospital operations, and we tested the Joint Commission on Accreditation of Healthcare Organizations 2004 National Patient Safety Goal, Section 6b to determine whether patient alarms could sufficiently compete against environmental background noises. Patient clinical alarms were audible at distances ofor = 95 feet with room doors open but were not sufficiently audible to hospital staff members when room doors were closed or during floor-buffing activities. This study suggests that, under these circumstances, hospitals may not meet Joint Commission on Accreditation of Healthcare Organizations 2004 National Patient Safety Goal, Section 6b. Because the audibility of patient clinical alarms directly affects patient safety, satisfaction, and quality of care, we provide recommendations for engineering controls and modifications to work routines.

La intususcepción de colon es una patología infrecuente en los adultos. En un 20 a 50% de los casos es secundaria a una enfermedad maligna. Sin embargo, en un número no despreciable, puede ser secundario a un lipoma. Como esta asociación es poco frecuente el diagnóstico preoperatorio sólo se realiza en pocos pacientes. El tratamiento en general es quirúrgico y depende de la presentación clínica. El presente trabajo describe las características clínicas, radiológicas y anatomopatológicas de dos pacientes que consultaron por un cuadro compatible con una obstrucción intestinal incompleta del colon. Se sospechó por las características de la tomografía computada en el primer enfermo y por los hallazgos de la colonoscopía en el segundo, la presencia de un lipoma de colon. Ambos pacientes fueron sometidos en forma electiva, a una resección del segmento de colon comprometido. Los dos enfermos evolucionaron sin complicaciones y fueron dados de alta al 10° y 8º día, posterior a la cirugía. El estudio anatomopatológico confirmó el diagnóstico preoperatorio de lipoma de colon en los 2 enfermos Colonic intussusception is uncommon among adults. In 20 to 50% of cases, it is secondary to malignant tumors. However, occasionally, it can be secondary to a lipoma. We report a 46 years old female and a 76 years old male with a colonic intussusception. The diagnosis was made in the female with an abdominal CAT scan that showed the lesion in the transverse colon, associated to an image with the density of fat. In the male, the diagnosis was made with a colonoscopy that showed a polypoid lesion that partially obstructed the ileocecal valve. Both patients were operated and the lesions were excised. The postoperative period was uneventful and they were discharged at the tenth and eighth postoperative day, respectively. The pathological study of the surgical piece confirmed the diagnosis of lipoma

El fenómeno de invaginación en el adulto es un evento poco frecuente, con una amplia variedad de presentación, que va desde síntomas agudos de obstrucción intestinal, hasta síntomas abdominales crónicos inespecíficos. Puede ocurrir tanto en intestino delgado como colon, siendo frecuente encontrar lesiones orgánicas subyacentes, en su mayoría procesos neoplásicos, tanto benignos como malignos Estos últimos son la etiología principal de invaginaciones en intestino grueso. El diagnóstico se puede realizar de forma confiable con el uso de tomografía computada al identificarse características imagenológicas particulares a esta patología. Reportamos dos casos en pacientes que se presentan con síntomas de obstrucción intestinal, con lesiones subyacentes en ambos casos, un lipoma y una neoplasia maligna Intussusception is an uncommon event in adults, with different clinical presentations, which range from bowel obstruction symptoms to nonspecific abdominal pain. Can occur in the small or large bowel. In adults there is usually an underlying cause, usually benign or malignant neoplasms, being the latter the main cause of this disease in the colon. The diagnosis with CT is usually straightforward, with a very typical appearance. We report two cases of patients with bowel obstruction and diagnosis of intussusception caused by a lipoma and colon cancer respectively

La listeriosis es un enfermedad bacteriana poco frecuente con una susceptibilidad mayor por mujeres embarazadas y especialmente por la unidad feto-placentaria. A continuación presentamos un caso ocurrido en el Hospital Central de la Policía, en que se logró confirmar el diagnóstico. Se reviso el tema y se estableció la diferencia en lo que respecta al manejo de este y otro tipo de corioamnionitis.