Purpose: This study was designed to seek associations between positron emission tomography/computed tomography (PET/CT) parameters, contrast enhanced neck computed tomography (CECT) and pathological findings, and to determine the potential prognostic value of PET/CT and CECT parameters in oral cavity squamous cell carcinoma (OCSCC).
Materials and method: 36 OCSCC patients underwent staging PET/CT and 30/36 of patients had CECT. PET/CT parameters were measured for the primary tumor and the hottest involved node, including maximum, mean, and peak standardized uptake values (SUV max, SUV mean, and SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized added metabolic activity (SAM), and normalized standardized added metabolic activity (N SAM). Qualitative assessment of PET/CT and CECT were also performed. Pathological outcomes included: perineural invasion, lymphovascular invasion, nodal extracapsular spread, grade, pathologic T and N stages. Multivariable logistic regression models were fit for each parameter and outcome adjusting for potentially confounding variables. Multivariable Cox proportional hazards models were used for progression free survival (PFS), locoregional recurrence free survival (LRFS), overall survival (OS) and distant metastasis free survival (DMFS).
Results: In multivariable analysis, patients with high (≥ median) tumor SUV max (OR 6.3), SUV mean (OR 6.3), MTV (OR 19.0), TLG (OR 19.0), SAM (OR 11.7) and N SAM (OR 19.0) had high pathological T-stage (T3/T4) (p < 0.05). Ring/heterogeneous pattern on CECT qualitative assessment was associated with worse DMFS and OS.
Conclusion: High PET/CT parameters were associated with pathologically advanced T stage (T3/T4). Qualitative assessment of CECT has prognostic value. PET/CT parameters did not predict clinical outcome.
Purpose: The purpose of this study is to report a case of microsporidial endophthalmitis after penetrating keratoplasty in a healthy patient and discuss the management.
Methods: This is a case report.
Results: A 69-year-old healthy male underwent penetrating keratoplasty for corneal scar secondary to herpes stromal keratitis. He presented with features of acute graft rejection 3 years later. After failure of medical management, a repeat full thickness keratoplasty was performed. Pathologic examination of the corneal specimen showed microsporidia. The patient then developed a chronic endophthalmitis, and a vitreous tap and injection followed by pars plana vitrectomy were performed. Pathologic examination of tissue showed microsporidia.
Conclusions: Microsporidia are being increasingly identified as the cause of stromal keratitis. This is the first report of microsporidial endophthalmitis in a patient without underlying systemic illness.
Objectives: To determine whether rhinovirus (RV) species is associated with more severe clinical illness in adults.Methods: Seventy-two RV-positive viral respiratory samples from adult patients were sequenced and analyzed phylogenetically after reverse transcriptase polymerase chain reaction of the region spanning the VP4 gene and 5' terminus of the VP2 gene. The clinical features and severity of illness associated with the different RV species were compared.Results: Phylogenetic analysis identified three distinct clusters as RV-A (54%), B (11%), or C (35%) species. In an unadjusted model, patients with RV-B infection were significantly more likely to have the composite outcome variable of death or intensive care unit admission (P = .03), but this effect diminished when controlling for patient sex. A logistic model of the relationship between RV species and adverse outcomes produced nonsignificant odds ratios when controlling for patient sex.Conclusions: Infection with RV-A or RV-B was associated with greater severity of illness in our adult population; however, the association disappeared after controlling for confounders.
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Carlton Dampier;
Beth Ely;
Darcy Brodecki;
Camille Coleman;
Leela Aertker;
Jocelyn Andrel Sendecki;
Benjamin Leiby;
Karen Kesler;
Terry Hyslop;
Marie Stuart
Background: The epidemiology of painful episodes in infants and younger children with SCD has not been well studied, particularly for pain managed at home. Procedure: SCD infants identified by newborn screening were enrolled in a longitudinal observational study of pain symptoms requiring parents to report the presence or absence of pain daily. When sickle cell related-pain events occurred, pain occurrence, location, associated symptoms and the treatment provided also were reported. Results: 103 children were enrolled at a median age of 7.2 months; 50 had an SS genotype, 32 SC, 6 SB0thalassemia, and 15 SB+thalassemia. Parents/guardians reported for a median of 3.8 years (range 0.3-7.6 years) assessing pain for a total of 141,197 days, excluding any period of recurrent transfusions, with an additional 28,079 days of missing data (16%). Children had pain reported on 2,288 days (1.6%), representing 768 distinct episodes of pain, of which 108 required hospitalizations (14%). Pain locations and symptoms consistent with dactylitis were most prevalent (80%) in the 0-12 month age group, and became progressively less prevalent thereafter. Group-based trajectory modeling of pain episode or pain day frequency identified several trajectory groups with progressively older ages of peak pain frequency, which included 40-45% of SS/SB0thalassemia and 10-12% of SC/SB+thalassemia children. Conclusions: Pain is relatively infrequent in SCD infants and young children and commonly managed at home. Analyses of longitudinal pain trajectories suggest several different pain trajectories, differing in their frequency, age of onset, and age at peak pain frequency with clinical implications for hydroxyurea management.
Infections with Mycobacterium tuberculosis (MTb) are globally prevalent in many countries, yet descriptions of placental pathology in tuberculous patients are scanty. The usual necrotizing granulomatous response associated with tuberculous infections requires an activation of the adaptive immune system. However, before this system is turned on, the 1st encounter with the tubercle bacillus is mediated by the innate immune system. This pathway utilizes innate surface receptors in neutrophils and histiocytes predominantly and does not produce a granulomatous pattern of inflammation. In this report we describe 2 cases of placental involvement with MTb in which an acute abscess-like inflammatory response with Myeloperoxidase and CD68-positive neutrophils and histiocytes causing acute villitis and intervillitis, with abundant acid-fast mycobacteria, were identified. Other cellular markers consistent with adaptive immunity were negative. These nongranulomatous lesions are seen in primary tuberculous infections occurring in a naïve woman and, obviously, a naïve fetus. These cases with early response inflammation in the placenta are frequently missed precisely because the mother is not known to be infected or has been recently diagnosed and because the symptoms in the newborn may not develop for several weeks, by which time the placenta may have been discarded. This report also shows that the differential diagnosis of acute villitis and intervillitis in the placenta should include tuberculosis aside from the more common bacterial infections such as listeriosis.
Sry-RelatedHMG-BOX-4(SOX4)isadevelopmental transcription factor that is overexpressed in as many as 23% of bladder cancer patients; however, the role of SOX4 in bladder cancer tumorigenesis is not yet well understood. Given the many roles of SOX4 in embryonic development and the context-dependent regulation of gene expression, in this study, we sought to determine the role of SOX4 in bladder cancer and to identify SOX4-regulated genes that may contribute to tumorigenesis. For this purpose, we employed a CRISPR interference (CRISPRi) method to transcriptionally repress SOX4 expression in T24 bladder cancer cell lines, ‘rescued’ these cell lines with the lentiviral-mediated expression of SOX4, and performed whole genome expression profiling. The cells in which SOX4 was knocked down (T24-SOX4-KD) exhibited decreased invasive capabilities, but no changes in migration or proliferation, whereas rescue experiments with SOX4 lentiviral vector restored the invasive phenotype. Gene expression profiling revealed 173 high confidence SOX4-regulated genes, including WNT5a as a potential target of repression by SOX4. Treatment of the T24-SOX4-KD cells with a WNT5a antagonist restored the invasive phenotype observed in the T24-scramble control cells and the SOX4 lentiviral-rescued cells. High WNT5a expression was associated with a decreased invasion and WNT5a expression inversely correlated with SOX4 expression, suggesting that SOX4 can negatively regulate WNT5a levels either directly or indirectly and that WNT5a likely plays a protective role against invasion in bladder cancer cells.
OBJECTIVES:: Nuclear factor-κB is a critical regulator of cell-survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase. DESIGN:: Prospective, randomized controlled study. SETTING:: Animal laboratories in university medical centers. SUBJECTS AND INTERVENTIONS:: Mice lacking functional NF-kB in their intestinal epithelium Vil-Cre/Ikkβf/δ and wild-type mice were subjected to sham laparotomy or cecal ligation and puncture. Animals were killed at 24 hours or followed 7 days for survival. MEASUREMENTS AND MAIN RESULTS:: Septic wild-type mice had decreased villus length compared with sham mice, whereas villus atrophy was further exacerbated in septic Vil-Cre/Ikkβf/δ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared with sham mice, which was further exacerbated in Vil-Cre/Ikkβf/δ mice. Sepsis induced intestinal hyperpermeability in wild-type mice compared with sham mice, which was further exacerbated in septic Vil-Cre/Ikkβ mice. This was associated with increased intestinal expression of claudin-2 in septic wild-type mice, which was further increased in septic Vil- Cre/Ikkβf/δ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following cecal ligation and puncture, and interleukin 10 and monocyte chemoattractant protein-1 levels were higher in septic Vil-Cre/Ikkβf/δ mice than in septic wild-type mice. All septic mice were bacteremic, but no differences in bacterial load were identified between wild-type and Vil-Cre/Ikkβf/ δ mice. To determine the functional significance of these results, animals were followed for survival. Septic wild-type mice had lower mortality than septic Vil-Cre/Ikkβf/δ mice (47% vs 80%, p < 0.05). Antitumor necrosis factor administration decreased intestinal apoptosis, permeability, and mortality in wild-type septic mice, and a similar improvement in intestinal integrity and survival were seen when antitumor necrosis factor was given to Vil-Cre/Ikkβf/δ mice. CONCLUSIONS:: Enterocyte-specific NF-kB has a beneficial role in sepsis by partially preventing sepsis-induced increases in apoptosis and permeability, which are associated with worsening mortality.
Under a number of stress or pathological conditions, actin and actin depolymerizing factor (ADF)/cofilin form rod-like structures that contain abnormal bundles of actin filaments that are heavily decorated with ADF/cofilin. However, the mechanism of actin rod formation and the physiological role of actin rods are not clearly understood. Here, we report that overexpression of green fluorescent protein-fused UNC-60B, a muscle-specific ADF/cofilin isoform, in Caenorhabditis elegans body wall muscle induces formation of rod-like structures. The rods contained GFP-UNC-60B, actin-interacting protein 1 (AIP1), and actin, but not other major actin-associated proteins, thus resembling actin-ADF/cofilin rods found in other organisms. However, depletion or overexpression of AIP1 did not affect formation of the actin-GFP-UNC-60B rods, suggesting that AIP1 does not play a significant role in the rod assembly. Truncation of the C-terminal tail, a putative F-actin binding site, of UNC-60B abolished induction of the rod formation, strongly suggesting that stable association of UNC-60B with F-actin, which is mediated by its C-terminus, is required for inducing actin-ADF/cofilin rods. This study suggests that C. elegans can be a new model to study functions of actin-ADF/cofilin rods.
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Steven C. Smith;
Kiril Trpkov;
Ying-Bei Chen;
Rohit Mehra;
Deepika Sirohi;
Chisato Ohe;
Andi K. Cani;
Daniel H. Hovelson;
Kei Omata;
Adeboye Osunkoya
An emerging group of high-grade renal cell carcinomas (RCCs), particularly carcinomas arising in the hereditary leiomyomatosis renal cell carcinoma syndrome (HLRCC), show fumarate hydratase (FH) gene mutation and loss of function. On the basis of similar cytomorphology and clinicopathologic features between these tumors and cases described as tubulocystic carcinomas with poorly differentiated foci (TC-PD) of infiltrative adenocarcinoma, we hypothesized a relationship between these entities. First, 29 RCCs with morphology of TC-PD were identified retrospectively and assessed for FH expression and aberrant succination (2SC) by immunohistochemistry (IHC), with targeted next-generation sequencing of 409 genes - including FH - performed on a subset. The 29 TC-PD RCCs included 21 males and 8 females, aged 16 to 86 years (median, 46), with tumors measuring 3 to 21 cm (median, 9) arising in the right (n=16) and left (n=13) kidneys. Family history or stigmata of HLRCC were identifiable only retrospectively in 3 (12%). These tumors were aggressive, with 79% showing perinephric extension, nodal involvement in 41%, and metastasis in 86%. Of these, 16 (55%) demonstrated loss of FH by IHC (14/14 with positive 2SC). In contrast, 5 (17%) showed a wild-type immunoprofile of FH+/2SC-. An intrigui ng group of 8 (28%) showed variable FH± positivity, but with strong/diffuse 2SC+. Next-generation sequencing revealed 8 cases with FH mutations, including 5 FH-/2SC+ and 3 FH±/2SC+ cases, but none in FH+/2SC- cases. Secondly, we retrospectively reviewed the morphology of 2 well-characterized cohorts of RCCs with FH-deficiency determined by IHC or sequencing (n=23 and n=9), unselected for TC-PD pattern, identifying the TC-PD morphology in 10 (31%). We conclude that RCCs with TC-PD morphology are enriched for FH deficiency, and we recommend additional workup, including referral to genetic counseling, for prospective cases. In addition, based on these and other observations, we propose the term "FH-deficient RCC" as a provisional term for tumors with a combination of suggestive morphology and immunophenotype but where genetic confirmation is unavailable upon diagnosis. This term will serve as a provisional nomenclature that will enable triage of individual cases for genetic counseling and testing, while designating these cases for prospective studies of their relationship to HLRCC.
Surgical cancer resection requires an accurate and timely diagnosis of the cancer margins in order to achieve successful patient remission. Hyperspectral imaging (HSI) has emerged as a useful, noncontact technique for acquiring spectral and optical properties of tissue. A convolutional neural network (CNN) classifier is developed to classify excised, squamous-cell carcinoma, thyroid cancer, and normal head and neck tissue samples using HSI. The CNN classification was validated by the manual annotation of a pathologist specialized in head and neck cancer. The preliminary results of 50 patients indicate the potential of HSI and deep learning for automatic tissue-labeling of surgical specimens of head and neck patients.