EEG before chimeric antigen receptor T-cell therapy and early after onset of immune effector cell-associated neurotoxicity syndrome.

BACKGROUND: Immune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy. OBJECTIVE: This study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy. STUDY DESIGN: EEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS. RESULTS: Twenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h. CONCLUSIONS: If confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment.

Characteristics of mucocutaneous vascular malformations drawn from a decade of a multidisciplinary committee experience.

Vascular malformations (VM) are congenital, benign, and relatively frequent lesions. Scant data have been published about the epidemiology, clinical presentation, and treatment of VM from a dermatologist's perspective. The substantial differences between subtypes, broad range of specialists consulted and confusing nomenclature used over previous years may hamper a correct diagnosis. The main objective of this study is to describe VM epidemiology. As a secondary endpoint we evaluate clinical characteristics, clinical-radiological correlation and treatment approaches. We carried out an observational, descriptive, retrospective study. Cases presented to the multidisciplinary committee of our hospital from 2009 to 2019 were retrieved. Electronic medical records, monthly committee reports and the iconographic archive were reviewed and statistically analyzed. Overall, venous malformations (VeM) are the most frequent VM, followed by capillary malformations (CM), arterioVeM and lymphatic malformations (LM). Considering only patients under 16, CMs are the most frequent ones. Capillary and LMs are larger than venous or arteriovenous. While CMs are usually asymptomatic, symptomatic cases are threefold more frequent in the other subtypes. Decisions on active or conservative management depend on VM size but not location or patient age. CMs are mainly treated with laser therapy; venous with sclerotherapy or surgery; arteriovenous with surgery and lymphatic with surgery or sirolimus. Dermatologists play an important role in VM diagnosis and management. Our 10-year multidisciplinary experience should contribute to the literature and represent a practical resource for clinicians and researchers.

Specific macrophage subsets accumulate in human subcutaneous and omental fat depots during obesity.

Obesity is a chronic inflammatory disease associated with adipose tissue macrophage (ATM) activation. ATMs from lean mice contribute to tissue homeostasis by their M2-oriented polarization, whereas obesity leads to an increase of M1 inflammatory ATMs that underlies obesity-related metabolic disorders. In humans, studies characterizing ATMs and their functional status are limited. Here we investigated ATM phenotype in visceral (VAT) and subcutaneous (SAT) adipose tissue from healthy lean and obese individuals using two molecules previously identified as markers of M1-like and M2-like/tissue-resident macrophages, the C-type lectin CLEC5A and the scavenger receptor CD163L1, respectively. CD163L1 was expressed by the majority of ATMs, and CD163L1+ ATM density was greater with respect to cells expressing the pan-macrophage markers CD68 or CD11b. ATM counts in SAT, but not in VAT, increased in obese compared to lean individuals, measured with the three markers. Accordingly, CD163L1, CD68 and ITGAM gene expression was significantly enhanced in obese with respect to control individuals only in SAT. CLEC5A+ ATMs had a proinflammatory profile and were abundant in the lean VAT, but their density diminished in obesity. The only ATM subset that increased its counts in the obese VAT had a mixed M1-like (CD11c+ CD163- CD209- ) and M2-like (CLEC5A- CD206+ ) phenotype. ATM expansion was dominated by a subset of M2-like macrophages (CD11c- CLEC5A- CD163+ CD206+ CD209+ ) in the obese SAT, with a minor contribution of a CD11c+ CLEC5A- ATM subpopulation. Thus, both SAT and VAT seems to limit inflammation during obesity by differentially altering their ATM subset composition.

Integrating Downstaging in the Risk Assessment of Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: Validation of Valentini's Nomograms and the Neoadjuvant Rectal Score.

BACKGROUND: Adjuvant chemotherapy is controversial in patients with locally advanced rectal cancer after preoperative chemoradiation. Valentini et al developed 3 nomograms (VN) to predict outcomes in these patients. The neoadjuvant rectal score (NAR) was developed after VN to predict survival. We aimed to validate these tools in a retrospective cohort at an academic institution. PATIENTS AND METHODS: VN and the NAR were applied to 158 consecutive patients with locally advanced rectal cancer treated with chemoradiation followed by surgery. According to the score, they were divided into low, intermediate, or high risk of relapse or death. For statistical analysis, we performed Kaplan-Meier curves, log-rank tests, and Cox regression analysis. RESULTS: Five-year overall survival was 83%, 77%, and 67% for low-, intermediate-, and high-risk groups, respectively (P = .023), according to VN, and 84%, 71%, and 59% for low-, intermediate-, and high-risk groups, respectively (P = .004), according to NAR. When the score was considered as a continuous variable, a significant association with the risk of death was observed (NAR: hazard ratio, 1.04; P < .001; VN: hazard ratio, 1.10; P < .001). CONCLUSION: We confirmed the value of these scores to stratify patients according to their individual risk when designing new trials.

Contribution of the Pubofemoral Ligament to Hip Stability: A Biomechanical Study.

PURPOSE: To determine the isolated function of the pubofemoral ligament of the hip capsule and its contribution to hip stability in external/internal rotational motion during flexion greater than 30° and abduction. METHODS: Thirteen hips from 7 fresh-frozen pelvis-to-toe cadavers were skeletonized from the lumbar spine to the distal femur with the capsular ligaments intact. Computed tomographic imaging was performed to ensure no occult pathological state existed, and assess bony anatomy. Specimens were placed on a surgical table in supine position with lower extremities resting on a custom-designed polyvinylchloride frame. Hip internal and external rotation was measured with the hip placed into a combination of the following motions: 30°, 60°, 110° hip flexion and 0°, 20°, 40° abduction. Testing positions were randomized. The pubofemoral ligament was released and measurements were repeated, followed by releasing the ligamentum teres. RESULTS: Analysis of the 2,106 measurements recorded demonstrates the pubofemoral ligament as a main controller of hip internal rotation during hip flexion beyond 30° and abduction. Hip internal rotation was increased up to 438.9% (P < .001) when the pubofemoral ligament was released and 412.9% (P < .001) when both the pubofemoral and teres ligament were released, compared with the native state. CONCLUSIONS: The hypothesis of the pubofemoral ligament as one of the contributing factors of anterior inferior hip stability by controlling external rotation of the hip in flexion beyond 30° and abduction was disproved. The pubofemoral ligament maintains a key function in limiting internal rotation in the position of increasing hip flexion beyond 30° and abduction. This cadaveric study concludes previous attempts at understanding the anatomical and biomechanical function of the capsular ligaments and their role in hip stability. CLINICAL RELEVANCE: The present study contributes to the understanding of hip stability and biomechanical function of the pubofemoral ligament.

How many patients with rheumatic diseases and TNF inhibitors treatment have latent tuberculosis?

OBJECTIVES: Spanish clinical guidelines recommend screening patients for tuberculosis (TB) before TNF inhibitors (TNFi) treatment. Our objective was to estimate the prevalence of TST seroconversion as an estimation of the prevalence of latent TB in patients with rheumatic diseases and TNFi treatment that have already been screened for tuberculosis. METHODS: TST, booster and chest x-ray were performed to patients with rheumatic diseases, TNFi treatment, negative tuberculin skin tests before treatment and that were attending the rheumatology Department of three different hospitals in Barcelona. According to the Spanish Society Rheumatology guidelines, these patients had not received TB prophylaxis treatment. RESULTS: One hundred and forty patients were included in the study. The tuberculin skin test was positive in 4.28% (n=6) of the patients. 50% of the patients were undergoing TNFi ≤ 2 years, being two of the patients only one year on the TNFi when a positive TST was detected. This shows that a conversion of the TST can occur even few months or years after the TNFi is started. CONCLUSIONS: The present study observed that 4.28% of patients with rheumatic diseases on TNFi who did not have performed a pre-treatment TB prophylaxis, had a conversion of the TST. Moreover, the conversion of the TST had been within the first two years of treatment in half of the patients of our cohort. In spite of these results, false TST positives in the diagnosis of latent TB cannot be excluded as an explanation for our results.

CD163L1 and CLEC5A discriminate subsets of human resident and inflammatory macrophages in vivo.

Macrophages (Mϕ) can be differentiated and polarized in vitro from human CD14(+) monocytes under the influence of GM-CSF (GM-Mϕ) and M-CSF (M-Mϕ). GM-Mϕs are proinflammatory and M-Mϕs have an anti-inflammatory phenotype. We found selective expression of the lectin C-type lectin domain family 5 member A (CLEC5A) transcripts in GM-Mϕs and the scavenger receptor CD163 molecule-like 1 (CD163L1) in M-Mϕs by microarray assay. In vitro, CD163L1 expression was induced by IL-10 and M-CSF and CLEC5A by inflammatory cytokines and cell adherence. In secondary lymphoid organs, their respective expression was restricted to CD68(+)/CD163(+) Mϕs that preferentially produced either TNF (CLEC5A(+)) or IL-10 (CD163L1(+)). Mϕs from healthy liver and colon tissue were mostly CD163L1(+), and CLEC5A(+) cells were scarce. In contrast, CLEC5A(+) Mϕs were abundant in the intestinal lamina propria from patients with inflammatory bowel disease (IBD), with higher numbers of CLEC5A(+)CD163L1(+) found compared with those in secondary lymphoid organs. CLEC5A(+) cells were CD14(+)CD209(-)CD11b(+)CD11c(+)TNF(+)IL-10(+), and single positive CD163L1(+) cells were CD14(-)CD209(+)CD11b(-)CD11c(-)TNF(-)IL-10(+) in healthy donors and had lost the ability to produce IL-10 and to express CD209 in those with IBD. In melanomas, CLEC5A(+) tumor-associated Mϕs (TAMs) were not detected in 42% of the cases evaluated, but CD163L1(+) TAMs were found in 100%. Similar to IBD, CD163L1(+) TAMs expressed high levels of CD209 and produced significant amounts of IL-10, and CLEC5A(+) TAMs were CD14(hi) and produced enhanced levels of TNF in metastases. Overall, these results suggest that CD163L1 expression is associated with tissue-resident Mϕs with an anti-inflammatory or anergic phenotype and that CLEC5A(+) Mϕs exhibit TNF-producing ability and might display a proinflammatory effect.

Evaluation of mesorectal fascia in mid and low anterior rectal cancer using endorectal ultrasound is feasible and reliable: a comparison with MRI findings.

BACKGROUND: Accuracy of MRI in assessing mesorectal fascia and predicting circumferential resection margin decreases in low anterior rectal tumors. OBJECTIVE: The purpose of this work was to evaluate the accuracy of endorectal ultrasound in predicting the pathologic circumferential resection margin in low rectal anterior tumors and to compare it with MRI findings. DESIGN: This was a prospective series comparing the preoperative circumferential resection margin assessed by endorectal ultrasound and MRI with pathologic examination. SETTINGS: The study was conducted by a specialized colorectal multidisciplinary team at a tertiary teaching hospital. PATIENTS: Between 2002 and 2008, 76 patients with mid to low rectal cancer were preoperatively evaluated by endorectal ultrasound and MRI and underwent total mesorectal excision without neoadjuvant radiochemotherapy. Twenty-seven patients with posterior or postero-lateral tumors were excluded, leaving 49 patients with anterior or antero-lateral tumors for the present subanalysis. We compared preoperative circumferential resection margin status using endorectal ultrasound and MRI with pathologic examination. INTERVENTIONS: We conducted a comparison between preoperative circumferential resection margin status and pathologic examination after total mesorectal excision surgery. MAIN OUTCOME MEASURES: Accuracy in predicting pathologic circumferential resection margin status was measured. RESULTS: Overall accuracy of endorectal ultrasound and MRI in assessing circumferential resection margin status was 83.7% and 91.8%, with negative predictive values of 97.2% and 97.5%. When focusing on low rectal tumors, the overall accuracy of endorectal ultrasound increased to 87.5%, whereas the accuracy of MRI decreased to 87.5%, with a negative predictive value of 95.6% for both diagnostic tests. LIMITATIONS: The sample size is small, and interobserver variability in radiologic assessment was not evaluated. CONCLUSIONS: Endorectal ultrasound can help MRI in predicting circumferential resection margin involvement in mid to low anterior rectal cancer, especially at the low third of the rectum, with a high negative predictive value.

Modified Wong's classification improves the accuracy of rectal cancer staging by endorectal ultrasound and MRI.

BACKGROUND: Douglas Wong proposed a new classification of tumor penetration in the rectal wall (T stage) in an attempt to incorporate the prognostic heterogeneity of T3 rectal cancers into the preoperative staging. OBJECTIVE: This study aimed to evaluate if the accuracy of endorectal ultrasound and MRI in predicting rectal cancer T staging improves when using a modified Wong's classification. DESIGN: This prospective series compares local standard TN staging and a modified Wong's classification. SETTINGS: This study was conducted by a specialized Colorectal Multidisciplinary Team at a tertiary teaching hospital. PATIENTS: Seventy patients underwent surgery for middle or low rectal cancer between 2002 and 2008 without neoadjuvant radiochemotherapy. We compared the preoperative staging with the pathological staging to determine the preoperative accuracy of endorectal ultrasound and MRI when using a modified Wong's classification vs the standard TN classification. INTERVENTIONS: A modified version of Wong's classification was used for preoperative and pathological staging. MAIN OUTCOME MEASURES: The primary outcome measured was the accuracy in the preoperative T staging. RESULTS: The overall accuracy of endorectal ultrasound and MRI in assessing T staging was 68.6% and 72.9% (uT1/2, 90%; uT3, 58.3%; and uT4, 100% and rT1/2, 88%; rT3, 63.4%; and rT4, 75%). By using the proposed modified Wong's classification, the overall accuracy of endorectal ultrasound and MRI improved to 82.9% and 90%. LIMITATIONS: The interobserver variability in radiological assessment was not evaluated. CONCLUSION: With use of the modified Wong's classification proposed in this study, the overall accuracy of preoperative imaging in assessing T staging of rectal cancer is substantially improved, especially when endorectal ultrasound and MRI stage match, enhancing the selection of patients for neoadjuvant radiochemotherapy.

Factores asociados a incontinencia urinaria en gestantes del Hospital II Suárez - Angamos EsSalud en el periodo Marzo-Mayo 2011 / Factors associated with urinary incontinence in pregnant women at the Hospital II Suarez - Angamos Essalud during the period March-May 2011

Objetivos: Determinar los factores asociados a Incontinencia Urinaria en gestantes del Hospital II Suárez-Angamos EsSalud en el periodo Marzo-Mayo 2011. Material y métodos: La muestra estuvo constituida por 144 gestantes atendidas en el periodo que corresponde al estudio. Los datos obtenidos durante la investigación, por medio de la ficha de recolección de datos elaborada para los fines de la investigación se ordenaron y procesaron, valiéndonos del programa SPSS 18.0 para Windows 2007. Resultados: La media de la edad de las pacientes con incontinencia urinaria fue de 32.1 +/- 7.8 años. Encontramos que de las pacientes que presentaron incontinencia urinaria hubo una mayor frecuencia de pacientes convivientes (96.7 por ciento), con grado de instrucción superior (55 por ciento), no multíparas (61.7 por ciento), que no era su primer embarazo (61.7 por ciento), que habían tenido una mayor frecuencia de partos vaginales en el 31.7 por ciento de los casos, que en su mayoría no fumaban (95 por ciento), no sufrían de constipación (65 por ciento), que tenían el antecedente familiar de incontinencia urinaria (55 por ciento). Conclusiones: Los factores asociados a Incontinencia Urinaria en gestantes del Hospital II Suárez-Angamos EsSalud en el periodo Marzo-Mayo 2011 fueron el antecedente familiar de incontinencia urinaria, disuria, y el antecedente de parto vaginal.

Preoperative chemoradiation may not always be needed for patients with T3 and T2N+ rectal cancer.

BACKGROUND: Preoperative chemoradiation is becoming the standard treatment for patients with locally advanced rectal cancer. However, since the introduction of total mesorectal excision (TME), local recurrence rates have been reduced significantly, and some patients can be spared from potentially toxic over treatment. The current study was designed to assess the factors that predict recurrence in an institutional series of patients with rectal cancer who had clinical T2 lymph node-positive (cT2N+) tumors or cT3N0/N+ tumors and underwent radical surgery without receiving preoperative chemoradiation. METHODS: Between November 1997 and November 2008, the authors' multidisciplinary group preoperatively staged 398 patients with rectal cancer by using endorectal ultrasonography and/or magnetic resonance imaging. The analysis included 152 consecutive patients with cT2N+, cT3N0, or cT3N+ rectal cancer who underwent TME without receiving preoperative chemoradiation. Macroscopic assessment of the mesorectal excision and circumferential resection margins were determined. Factors potentially related to local recurrence (LR), disease-free survival (DFS) and cancer-specific survival (CSS) were analyzed. RESULTS: After a median follow-up of 39 months, the 5-year actuarial LR, DFS, and CSS rates were 9.5%, 65.4%, and 77.8%, respectively, for the whole group. Threatened mesorectal fascia at preoperative staging was the only independent preoperative factor that predicted a higher risk for LR (P = .007), shorter DFS (P = .007), and shorter CSS (P = .05). In particular, the 5-year LR rates for patients with and without preoperative threatened circumferential resection margins were 19.4% and 5.4%, respectively. CONCLUSIONS: The current results suggested that patients with rectal cancer clinically staged as T3N0/N+ or T2N+ with a free margin >2 mm from mesorectal fascia may undergo TME alone, avoiding over treatment with preoperative chemoradiation.

[Splenectomy in autoimmune hematological diseases. Comparative study between laparoscopic and open technique]. / Esplenectomía en pacientes con enfermedades hematológicas autoinmunes. Estudio comparativo entre técnicas laparoscópica y abierta.

BACKGROUND: We undertook this study to compare the outcome of laparoscopic and open splenectomy in the treatment of hematological diseases. METHODS: This was a comparative study of two groups of patients. The study sample consisted of 37 patients divided into two groups: group I, open splenectomy (OS) and group II, laparoscopic splenectomy (LS). Twenty one consecutive patients with LS were compared to 16 randomized patients selected from clinical records of OS patients. General and specific variables were collected in Microsoft Access database and analyzed in SPSS for Windows statistical program. Statistical analysis was done. RESULTS: Of 25 women and 12 men (37.2 +/- 16.9 years old), 6 had autoimmune hemolytic anemia, 29 idiopathic thrombocytopenic purpura (ITP), and two had Evans syndrome. Patients with ITP had preoperative platelet count of 74.6 +/- 64.1/mm(3) and patients with autoimmune hemolytic anemia had a preoperative hemoglobin of 10.6 +/- 2.9 g/dl. Ten patients had co-morbidity. There were 16 OS and 21 LS. Size of spleen was 13.1 +/- 3.7 cm and weight was 178 +/- 115 g. Surgical time for OS was 69.3 +/- 21.7 min and for LS was 152.8 +/- 61.1 min (p <0.05). Operative bleeding for OS was 300 +/- 265 ml and for LS it was 265 +/- 198 ml (p >0.05). One patient in LS group had red cell transfusion and two in the same group had to be converted to OS to reassure hemostasis. Reoperations had to be done in the OS group, two to control bleeding and one with a left lobe hepatic hematoma. There was no mortality. Postoperative platelet count in patients with ITP increased to 246 +/- 159 and hemoglobin in patients with hemolytic anemia increased to 12.1 +/- 3.6 g (p <0.05). Hospital stay in OS was 5.06 +/- 3.6 days vs. 2.06 +/- 0.26 in LS (p <0.05). Patients in OS had 30.6 +/- 10.5 lost work days vs. 15.5 +/- 4.6 in LS group (p <0.05). CONCLUSIONS: It is possible to treat patients with hematological diseases with LS. LS is time-consuming compared to OS. Morbidity in LS may be less than in OS. Mortality may be zero. Hospital stay and postoperative lost work days are less in LS than with OS. LS may be the gold standard in treatment of patients with hematological diseases.

Compensatory activations in patients with multiple sclerosis during preserved performance on the auditory N-back task.

Recent fMRI studies have suggested that multiple sclerosis (MS) patients show adaptive cortical changes (i.e., compensatory mechanisms) during motor and cognitive tasks to limit the clinical impact of tissue injury. In this study, we investigated the activation pattern during the auditory n-back working memory (WM) paradigm in a group of 17 MS patients and 10 healthy controls with preserved performance in WM tasks. Compared with healthy controls, MS patients showed significantly greater bilateral activation in prefrontal cortex (BA 44), and the insula. These findings were similar to those obtained in previous studies showing that compensatory mechanisms during WM tasks in MS may be based on the use of prefrontal areas adjacent to those involved in the task.

[Inferior vena cava malformations and deep venous thrombosis]. / Anomalías de la vena cava y trombosis venosa profunda.

We carried out a prospective study of 116 patients under 50 years of age who had deep venous thrombosis of the lower extremities to determine whether the presence of congenital anomaly of the inferior vena cava (IVC) was a risk factor for the disease. All patients were investigated by Doppler echography. Some 37 patients who had iliac vein occlusion also underwent phlebography. In 10 patients in whom the IVC was difficult to image, magnetic resonance angiography or computerized axial tomography was carried out. In all patients, studies of antithrombin, protein C and protein S deficiency, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, and acquired risk factors were also performed. Of the 37 patients who had iliac vein occlusion, six had an IVC anomaly. Two of these patients had antiphospholipid antibodies, while another had prothrombin G20210A. Two patients with an anomaly had recurrent thrombotic occlusion. In conclusion, congenital IVC anomalies were present in 16.2% (95% confidence interval, 6.2-32%) of young patients with iliac thrombosis.