Cortical Thinning in High-Grade Asymptomatic Carotid Stenosis / 대한뇌졸중학회지

Background@#and Purpose High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere. @*Methods@#We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis–Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis. @*Results@#Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032). @*Conclusions@#Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

Diffuse large B-cell lymphoma (DLBCL) is infiltrated with activated CD8+ T-cells despite immune checkpoint signaling

Background@#B-cell non-Hodgkin lymphomas (NHL) are hematologic malignancies that arise in the lymph node. Despite this, the malignant cells are not cleared by the immune cells present.The failure of anti-tumor immunity may be due to immune checkpoints such as the PD-1/PDL-1 axis, which can cause T-cell exhaustion. Unfortunately, unlike Hodgkin lymphoma, checkpoint blockade in NHL has shown limited efficacy. @*Methods@#We performed an extensive functional analysis of malignant and non-malignant lymph nodes using high dimensional flow cytometry. We compared follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and lymph nodes harboring reactive hyperplasia (RH). @*Results@#We identified an expansion of CD8+PD1+ T-cells in the lymphomas relative to RH. Moreover, we demonstrate that these cells represent a mixture of activated and exhausted T-cells in FL. In contrast, these cells are nearly universally activated and functional in DLBCL. This is despite expression of counter-regulatory molecules such as PD-1, TIM-3, and CTLA-4, and the presence of regulatory T-cells. @*Conclusion@#These data may explain the failure of single-agent immune checkpoint inhibitors in the treatment of DLBCL. Accordingly, functional differences of CD8+ T-cells between FL and DLBCL may inform future therapeutic targeting strategies.

Prognostic predictors of lymph node metastasis in penile cancer: a systematic review

ABSTRACT Purpose: Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic factor is the presence of inguinal lymph node metastases (ILNM) at the time of diagnosis. At least 25% of cases have micrometastases at the time of diagnosis. Therefore, we performed a literature review of studies evaluating factors, both clinical and pathological, predictive of lymph node metastases in penile SCC. Materials and methods: Studies were identified using PubMed and search terms included the following: penile cancer, penile tumor, penile neoplasm, penile squamous cell carcinoma, inguinal lymph node metastasis, lymph node metastases, nodal metastasis, inguinal node metastasis, inguinal lymph node involvement, predictors, and predictive factor. The number of patients and predictive factors were identified for each study based on OR, HR, or RR in multivariate analyses, as well as their respective significance values. These were compiled to generate a single body of evidence supportive of factors predictive of ILNM in penile SCC. Results: We identified 31 studies, both original articles and meta-analyses, which identified factors predictive of metastases in penile SCC. The following clinical factors were predictive of ILNM in penile SCC: lymphovascular invasion (LVI), increased grade, increased stage (both clinical and pathological), infiltrative and reticular invasion, increased depth of invasion, perineural invasion, and younger patient age at diagnosis. Biochemically, overexpression of p53, SOD2, Ki-67, and ID1 were associated with spread of SCC to inguinal lymph nodes. Diffuse PD-L1 expression, increased SCC-Ag expression, increased NLR, and CRP >20 were also associated with increased ILNM. Conclusions: A multitude of factors are associated with metastasis of SCC of the penis to inguinal lymph nodes, which is associated with poor clinical outcomes. The above factors, most strongly LVI, grade, and node positivity, may be considered when constructing a nomogram to risk-stratify patients and determine eligibility for prophylactic inguinal lymphadenectomy.

A Stabilizing Agent, PCA/DTPA, Improves Plasma Storage Life for the Chromsystems Vitamin C Assay up to Six Months

The commonly used Chromsystems vitamin C (ascorbate) assay (Munich, Germany) has a sample storage life of five days at –20°C. Stabilizing agents have been successfully used to increase longevity; however, their suitability with this commercial assay is unclear. We investigated the compatibility of a stabilizing agent, perchloric acid/diethylenetriaminepentaacetic acid (PCA/DTPA), with the Chromsystems assay. Plasma was stored at –80°C, with or without PCA/DTPA. Storage up to six months was assessed through baseline and repeat analyses, stability was assessed by comparing paired non-stabilized and PCA/ DTPA-stabilized plasma, and performance was assessed using allowable performance specifications of an external quality assurance program. Ascorbate concentration was significantly lower in non-stabilized plasma than in paired PCA/DTPA-stabilized plasma, with a proportional difference of 11% (P = 0.01). All storage analysis results were within the allowable performance specifications. Storage at –80°C prevented plasma ascorbate oxidation; however, substantial oxidation occurred during sample processing. In conclusion, PCA/DTPA significantly reduces ascorbate oxidation, and PCA/DTPA-stabilized ascorbate plasma is compatible with the Chromsystems assay and stable for up to six months, when stored at –80°C.

A Case of Cervical Radiculopathy Related to a Cervical Manual Therapy Course

ABSTRACT Neck pain is a common problem associated with considerable comorbidities, disability and cost to society. Spinal manual therapy is commonly used to treat this condition, and some countries recommend it as a treatment option in their clinical guidelines, since it is generally believed to be a safe and effective method for physicians to use to relieve neck pain. However, the non-invasive and frequently medication-free manipulation manoeuvres can potentially lead to severe adverse effects. This study presents a case of cervical radiculopathy related to cervical manual therapy applied during a training course.

Bone Loss During the Acute Stage Following Burn Injury: Is It Local or Systemic? / La pérdida ósea durante la etapa aguda después de una lesión por quemaduras, ¿es local o sistémica?

ABSTRACT Objective: To examine post-burn bone loss and determine whether it was local or diffuse. Methods: Thirty-six patients with burn injuries were investigated, and the total body surface area of the burns and their locations were recorded. The bone mineral densities of the lumbar 1-4 vertebrae, bilateral distal forearm, and bilateral proximal femur of the patients were recorded, and these were compared with the measurements of the non-burnt extremity. Results: No statistically significant correlations existed among the total body surface area of the burns, their severity and the z-scores. In addition, when comparing the z-scores of the burnt extremity with those of the non-burnt extremity, no statistically significant difference was found (p > 0.05). Conclusion: In this study, a remarkable decrease in bone mass occurred during the second month following the burn injuries. The post-burn bone loss could not be correlated with the severity of the burns, but these injuries caused systemic bone loss.

RESUMEN Objetivo: Examinar la pérdida ósea después de una quemadura y determinar si era local o difusa. Métodos: Se investigó a 36 pacientes con lesiones por quemaduras y se registró el área total de la superficie del cuerpo con quemaduras y sus ubicaciones. Las densidades minerales óseas de las vértebras lumbares 1-4, del antebrazo distal bilateral, y del fémur proximal bilateral de los pacientes, fueron registradas y comparadas con las mediciones de la extremidad sin quemaduras. Resultados: No existieron correlaciones estadísticamente significativas entre el área total de la superficie corporal de las quemaduras, su severidad y las puntuaciones z. Además, al comparar las puntuaciones z de la extremidad quemada con las de la extremidad no quemada, no se encontró ninguna diferencia estadísticamente significativa (p > 0.05). Conclusión: En este estudio, se observó la ocurrencia de una disminución notable de la masa ósea durante el segundo mes tras las lesiones de la quemadura. La pérdida ósea posterior a las quemaduras no se pudo correlacionar con la severidad de las quemaduras, pero estas lesiones por quemadura causaron pérdida sistémica del hueso.

Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma

BACKGROUND: Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. METHODS: This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m² IV d 1, 2), etoposide (200 mg/m² IV d 1–3), and dexamethasone (40 mg PO d 1–4) followed by filgrastim (10 mcg/kg/d sc. through collection). RESULTS: We successfully collected stem cells from all patients, with a median of 7.9×10⁶/kg of body weight (range, 4.4 to 17.3×10⁶/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). CONCLUSION: For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.

Nutritional Management of Kidney Stones (Nephrolithiasis)

The incidence of kidney stones is common in the United States and treatments for them are very costly. This review article provides information about epidemiology, mechanism, diagnosis, and pathophysiology of kidney stone formation, and methods for the evaluation of stone risks for new and follow-up patients. Adequate evaluation and management can prevent recurrence of stones. Kidney stone prevention should be individualized in both its medical and dietary management, keeping in mind the specific risks involved for each type of stones. Recognition of these risk factors and development of long-term management strategies for dealing with them are the most effective ways to prevent recurrence of kidney stones.

Trends in the mortality of non-traumatic subarachnoid hemorrhage in Colombia: a 10-year analysis of a nationwide registry / Tendencias na mortalidade relacionada a hemorragia subaracnoidea na Colombia: analise de um registro nacional de 10 anos

Objective To assess trends in mortality from 1999 to 2008 resulting from non-traumatic subarachnoid hemorrhage (SAH) in the Colombian population. Method This population-based study analyzed all deaths by assuming a Poisson model. Results Subarachnoid hemorrhage-related deaths showed a statistically significant increase of 1.6% per year (p<0.001). The age-standardized analysis demonstrated an increased mortality trend of 3.3% per year (p<0.001) in people older than 70 years, but a decreased mortality trend in people younger than 50. It remained stable in patients 50-69 years old. Conclusion The overall SAH-related mortality rate in Colombia has increased because increased mortality among the elderly has been counterbalanced by reduced mortality rates in younger age groups. These disparities may reflect epidemiologic transition, treatment inequities, or a less favorable comorbid profile. .

Objetivo Avaliar as tendências da mortalidade relacionada a hemorragia subaracnóidea não-traumática (HSA) entre 1999 e 2008, na Colômbia. Método Foi realizado um estudo de base populacional, com base na análise das causas de morte, assumindo um modelo de Poisson. Resultados A incidência de mortes relacionadas a SAH mostrou um aumento estatisticamente significativo de 1,6% ao ano (p<0,001) para toda a população. A análise ajustada por idade demonstrou aumento da mortalidade de 3,3% ao ano (p<0,001) em pessoas com mais de 70 anos de idade, diminuição em pessoas com menos de 50 anos de idade e estabilidade em pessoas com idade entre 50 e 69 anos. Conclusão A taxa geral de mortalidade relacionada a SAH na Colômbia aumentou, porque o aumento da mortalidade entre os idosos foi maior que a redução nas taxas de mortalidade em grupos etários mais jovens. Estas disparidades podem refletir transição epidemiológica, as desigualdades de tratamento ou um perfil de comorbidades menos favorável. .

Pattern of medical diseases and determinants of prognosis of hospitalization during 2005 muslim pilgrimage [hajj] in a tertiary care hospital. A prospective cohort study

To document the pattern of medical diseases necessitating admission in a tertiary care hospital during Muslim pilgrimage [Hajj]. To assess the risk factors associated with mortality during hospitalization. The study was conducted at Al Noor Specialist Hospital, a 550-bed tertiary care teaching hospital, in Makkah, KSA. The participants included all Hajj patients admitted in the Department of Medicine in a 5-week period [January 3 to February 6, 2005] during the 2005 [1425 AH] Hajj. Information about demographics; past medical history; pre-Hajj functional status; presence of language barrier and translator availability; diagnosis for admission and complications during hospitalization including mortality was obtained prospectively using a standardized form. Six hundred and eighty-nine patients, belonging to 49 countries, with mean age of 62 years and male:female ratio of 1.8:1 were admitted. Two hundred-twenty [31.9%] had diabetes mellitus, 256 [37.2%] had hypertension, 219 [31.8%] had cardiac disease, and 103 [14.9%] patients had chronic lung disease. Of the 449 [65.2%] patients assessed, 284 [63.2%] patients had language barrier, and translator was not available for 152 [53.5%] of them. Pre-Hajj functional status assessment of 240 patients showed that 20 [8.3%] required assistance in performing activities of daily living [ADL], and 40 [16.7%] could not walk for half kilometer without difficulty. Common causes of morbidity were: 235 [34.1%] cardiovascular, 137 [19.9%] infectious and 85 [12.3%] neurological diseases. One hundered and fourteen [16.5%] patients died, with the common causes being pneumonia [28 patients], acute coronary syndrome [21], and stroke [20]. The risk factors associated with higher mortality were older age [65 +/- 1 versus 61 +/- 0.6 years, p=0.008], prior history of chronic lung disease [crude odds ratio, 1.81, p=0.034], dependence in any ADLs [4.90, p=0.025], inability to ambulate for half kilometer without difficulty [4.17, p=0.017] and non-availability of translator for patients with language barrier [5.51, p<0.0001]. Most patients were elderly with high prevalence of chronic medical disorders. Non-infectious diseases accounted for most morbidity and mortality. Pre-Hajj functional assessment should be carried out to identify patients at high risk of mortality. Provision of translator services for patients with language barrier is essential to improve future outcomes

Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in urological malignancies.

Several studies suggest that cellular adhesion molecules (CAM) play a role in cancer progression and metastasis. To evaluate the role of these molecules as possible tumor markers in patients with urological malignancies, we examined the serum levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular cellcular adhesion molecule-1 (VCAM-1) and E-selectin in patients with renal cell-, bladder-, prostate- and testicular cancer. Serum levels of 237 patients with urological cancers, renal cell carcinoma (n = 47), bladder cancer (n = 81), prostate cancer (n = 87) and testicular cancer (n = 22) and a group of 41 patients with benign prostate hyperplasia (BPH) as well as a 42 healthy control persons were examined for CAMs by specific ELISA tests. Serum CAM concentrations of all tumor patients were compared with controls and within the group according to T stage, N stage, tumor grade and extent of distant metastasis. Our results demonstrate that ICAM-1 and VCAM-1 serum levels are not stage dependently elevated; in contrary, they demonstrate a wide range and are highly variable throughout the different cancer types. In renal cell cancer and in bladder cancer, there is a significant difference for ICAM-1 between controls and T3 and T4 and metastatic cancers. A similar difference was found for VCAM-1, however not for E-selectin in any tumor group. Testicular cancer and prostate cancer did not demonstrate any difference in CAM serum levels between patients with tumors and controls. In metastatic renal cell-, bladder- and prostate cancer, the serum levels of ICAM-1 and VCAM-1 showed a tendency to correlate with the extent of metastatis although no statistical difference between patients with a single metastatic lesion and patients with multiple lesions could be demonstrated. The results of this study implicate a rather limited role of cellular adhesion molecules. Despite of significant ICAM-1 or VCAM-1 serum levels in some locally advanced tumors or metastatic disease, this observation does not provide enough relevant clinical information for use as tumor markers.