- Factors Associated with Persistent Sputum Positivity at the End of the Second Month of Tuberculosis Treatment in Lithuania. [Journal Article]
- TRTuberc Respir Dis (Seoul) 2018 Jun 19
- CONCLUSIONS: In conclusion, higher sputum smear and culture grading at diagnosis, shorter TTD, higher number of lobes involved, cavitation, male sex, alcohol abuse, and lower BMI were independently associated with persistent sputum positivity. These factors should be sought when distinguishing which patients will remain infectious longer and possibly have worse outcomes.
- Segmental Colitis Associated Diverticulosis-A Possible Diagnosis in Teenagers. [Journal Article]
- FPFront Pediatr 2018; 6:168
- Segmental colitis associated with diverticulosis (SCAD) is manifested by active chronic inflammation of the colonic segments affected by diverticulosis, luminal-mucosal inflammation, independent of t...
Segmental colitis associated with diverticulosis (SCAD) is manifested by active chronic inflammation of the colonic segments affected by diverticulosis, luminal-mucosal inflammation, independent of the presence of inflammation within and/or around the diverticula, and it usually spares the rectum. We present the case of a 15-year-old female admitted to our clinic due to lower digestive hemorrhage and abdominal pain in the previous week, associated with fever 1 day prior to admission. The patient had pallor, painful abdomen upon palpation, accelerated bowel movements, and macroscopic evidence of blood in the stools. Initial laboratory tests showed leukocytosis with neutrophilia, thrombocytosis, anemia, and elevated inflammatory biomarkers. Moreover, colonoscopy revealed multiple ulcerations, hemorrhage, and edema of the sigmoid colon; however, multiple orifices raised the suspicion of a colonic diverticulosis and this was later on confirmed through a barium enema. The histopathological examination pointed out signs of an active chronic inflammation and mucosal architectural changes associated with crypt abscesses, therefore suggesting the diagnosis of SCAD. The patient's prognosis was favorable; her condition improved following steroid and 5-aminosalicylate therapy, without any symptoms or recurrences at the 4 months follow-up. In conclusion, SCAD is a very rare disease entity that is usually confused with other inflammatory bowel conditions. Moreover, it has not been reported in the pediatric age group until now.
- Defective cholesterol metabolism in haematopoietic stem cells promotes monocyte-driven atherosclerosis in rheumatoid arthritis. [Journal Article]
- EHEur Heart J 2018 Jun 14; 39(23):2158-2167
- CONCLUSIONS: Rheumatoid arthritis impairs atherosclerotic regression and alters progression, which is associated with an expansion of myeloid cells and disturbed cellular cholesterol handling, independent of plasma cholesterol levels. Infusion of rHDL prevented enhanced myelopoiesis and monocyte entry into lesions. Targeting cellular cholesterol defects in people with RA, even if plasma cholesterol is within the normal range, may limit vascular disease.
- An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors. [Journal Article]
- CDCancer Discov 2018 Jun 08
- By leveraging tumorgraft (PDX) RNA-Seq data, we developed an empirical approach, DisHet, to dissect the tumor microenvironment (eTME). We found that 65% of previously defined immune signature genes a...
By leveraging tumorgraft (PDX) RNA-Seq data, we developed an empirical approach, DisHet, to dissect the tumor microenvironment (eTME). We found that 65% of previously defined immune signature genes are not abundantly expressed in Renal Cell Carcinoma (RCC), and identified 610 novel immune/stromal transcripts. Using eTME, genomics, pathology and medical record data involving >1,000 patients, we established an inflamed pan-RCC subtype (IS) enriched for Tregs, NK cells, Th1 cells, neutrophils, macrophages, B cells, and CD8+ T cells. IS is enriched for aggressive RCCs, including BAP1-deficient clear-cell and type 2 papillary tumors. The IS subtype correlated with systemic manifestations of inflammation such as thrombocytosis and anemia, which are enigmatic predictors of poor prognosis. Furthermore, IS was a strong predictor of poor survival. Our analyses suggest that tumor cells drive the stromal immune response. These data provide a missing link between tumor cells, the TME, and systemic factors.
- Poor prognostic role of the pretreatment platelet counts in colorectal cancer: A meta-analysis. [Review]
- MMedicine (Baltimore) 2018; 97(23):e10831
- CONCLUSIONS: In this meta-analysis, we suggest that an elevated platelet count is a negative predictor of survival in both primary colorectal cancer and resectable colorectal liver metastases.
- Successful replantation of 2 digits in a patient with thrombocytosis after splenectomy: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(22):e10951
- CONCLUSIONS: In patients with digital amputation, replantation can be attempted, even when thrombocytosis is expected, when requested by the patient. Furthermore, the platelet count should be actively controlled with medication to improve the survival rate of the reattached finger.
- Platelet Characteristics in Patients with Essential Thrombocytosis. [Journal Article]
- CBCytometry B Clin Cytom 2018 May 23
- CONCLUSIONS: The study showed that ET patients compared to healthy individuals have an increased amount of reticulated platelets and increased aggregation potential. These findings might in part explain the increased thromboembolic risk in patients with ET This article is protected by copyright. All rights reserved.
- Intrinsic apoptosis circumvents the functional decline of circulating platelets, but does not cause the storage lesion. [Journal Article]
- BloodBlood 2018 May 21
- The circulating life span of blood platelets is regulated by the pro-survival protein BCL-XL. It restrains the activity of BAK and BAX, the essential pro-death mediators of intrinsic apoptosis. Disab...
The circulating life span of blood platelets is regulated by the pro-survival protein BCL-XL. It restrains the activity of BAK and BAX, the essential pro-death mediators of intrinsic apoptosis. Disabling the platelet intrinsic apoptotic pathway in mice by deleting BAK and BAX results in a doubling of platelet life span and concomitant thrombocytosis. Apoptotic platelets expose phosphatidylserine (PS) via a mechanism that is distinct from that driven by classical agonists. Whether there is any role for apoptotic PS in platelet function in vivo, however, is unclear. Apoptosis has also been associated with the platelet storage lesion (PSL), the constellation of biochemical deteriorations that occur during blood bank storage. In this study, we investigated the role of BAK/BAX-mediated apoptosis in hemostasis and thrombosis, and in the development of the PSL. We show that while intrinsic apoptosis is rapidly induced during storage at 37°C, it is not detected when platelets are kept at the standard storage temperature of 22°C. Remarkably, loss of BAK and BAX did not prevent the development of the PSL at either temperature. BAK/BAX-deficient mice exhibited increased bleeding times and unstable thrombus formation. This phenotype was not caused by impaired PS exposure, but associated with a defect in granule release from aged platelets. Strikingly, rejuvenation of BAK/BAX-deficient platelets in vivo completely rescued the observed hemostatic defects. Thus, apoptotic culling of old platelets from the bloodstream is essential to maintain a functional, hemostatically reactive platelet population. Inhibiting intrinsic apoptosis in blood banked platelets is unlikely to yield significant benefit.
- Sustained Regression of Hydroxycarbamide Induced Actinic Keratoses after Switching to Anagrelide. [Journal Article]
- CRCase Rep Dermatol Med 2018; 2018:2874012
- Hydroxycarbamide (HC) is the first-line treatment for certain myeloproliferative neoplasms, such as polycythemia vera and essential thrombocytosis (ET). In a subset of these patients long-term treatm...
Hydroxycarbamide (HC) is the first-line treatment for certain myeloproliferative neoplasms, such as polycythemia vera and essential thrombocytosis (ET). In a subset of these patients long-term treatment with HC can result in the development of confluent actinic keratoses (AK) followed by invasive keratinocytic carcinomas ("squamous dysplasia"), preferentially on sun-exposed skin. Discontinuation or dose reduction of HC may result in partial improvement. A 59-year-old farmer after 14 years on HC (2 gr/d) and acetylsalicylic acid (100 mg/d) for ET, was referred for numerous, hyperkeratotic AK on face, scalp, and hands that could not be controlled with repeated (N = 15) cryosurgery sessions in the previous 3 years. Acitretin (0.32 mg/kg daily) and topical treatments (cryosurgery with ingenol mebutate) were initiated with only marginal improvement after 3 months. Acitretin dose was doubled and HC was switched to anagrelide (0.5 mg twice daily). Within a month the AK load regressed significantly and, at 3 months follow-up, complete clinical remission was achieved and acitretin was discontinued. Twenty months later the patient is clear from AK. In conclusion, the impressive and sustainable AK remission under anagrelide draws attention to a possible role of the phosphodiesterase 3 pathway, the major pharmacological target of anagrelide, as a potential therapeutic target for keratinocytic cancers.
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- Preoperative SCC-Ag and thrombocytosis as predictive markers for pelvic lymphatic metastasis of squamous cervical cancer in early FIGO stage. [Journal Article]
- JCJ Cancer 2018; 9(9):1660-1666
- Objectives: To explore the clinical significance of squamous cell carcinoma antigen (SCC-Ag) and thrombocytosis to predict pelvic lymphatic metastasis (PLM) of squamous cervical cancer (SCC) in Inte...
Objectives: To explore the clinical significance of squamous cell carcinoma antigen (SCC-Ag) and thrombocytosis to predict pelvic lymphatic metastasis (PLM) of squamous cervical cancer (SCC) in International Federation of Gynecology and Obstetrics (FIGO) stages IA-IIA. Methods: A retrospective clinicopathologic review of 782 patients of a primary cohort in three Chinese hospitals from 2010 to 2015, and 407 patients of a validation cohort in another institution from 2015 to 2017. A receiver operating characteristic curve was used to determine the optimal SCC-Ag threshold to predict PLM in the groups. Univariate and multivariate logistic analyses for PLM were performed to assess differences in outcome. Results: In the primary and validation cohort, 15.6% (122/782) and 25.3% (103/407) patients were classified into the thrombocytosis group (platelet count >300 × 109/L), respectively. Optimal cutoff values of SCC-Ag for predicting PLM of the thrombocytosis group and the normal group were 3.26 ng/mL (AUC 0.754; sensitivity 73.08%; specificity 72.92%; P = 0.000) and 4.58 ng/mL (AUC 0.706; sensitivity 53.26%; specificity 83.98%; P = 0.000), respectively, in the primary cohort, and 1.55 ng/mL (AUC 0.705; sensitivity 79.31%; specificity 55.41%; P = 0.000) and 1.75 ng/mL (AUC 0.655; sensitivity 69.57%; specificity 64.26%; P = 0.000), respectively, in the validation cohort. In multivariate logistic analysis, preoperative SCC-Ag over 3.26 ng/mL and lymphovascular space involvement were the significant predictors of PLM for SCC in FIGO stages IA-IIA. Conclusions: Preoperative SCC-Ag alone or combined with thrombocytosis might be used as predictive markers for PLM before initial treatment in early stage SCC.