Nasal Pyriform Aperture Stenosis in a Newborn: When to Operate.

Congenital nasal pyriform aperture stenosis (CNPAS) is a very rare cause of neonatal respiratory distress and is often missed because of its rarity. It arises from the overgrowth of the nasal process of the maxilla. Maxillofacial CT scan findings of pyriform aperture width <11 mm in a full-term baby, median central incisor, triangular-shaped palate, and median palatal ridge confirm the diagnosis. We describe here a case of CNPAS admitted with respiratory distress that increased further on feeding. An infant feeding tube of size 6 was not negotiable through the nostrils. Resistance was appreciated at the inlet of the nostril. Maxillofacial CT showed pyriform aperture stenosis of 3.4 mm, suggesting CNPAS. The child could not be weaned off a high-flow nasal cannula despite conservative management with decongestants, steroids spray, dilatation, and stenting for 20 days. Subsequently, surgical widening of the nasal aperture by a sublabial approach was done. The child was discharged on the 10th postoperative day on full oral feeds. It is important to suspect CNPAS in neonates with respiratory distress where other common causes have been ruled out, as it can be treated by surgery in cases refractory to conservative management.

Determinants of outcomes and advances in CD19-directed chimeric antigen receptor therapy for B-cell acute lymphoblastic leukemia.

Relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive B-cell neoplasm associated with poor outcomes. Conventional multiagent chemotherapy and bispecific antibody therapy may induce remission; however, relapse rates remain high and overall survival is poor. Chimeric antigen receptor T-cell (CAR-T) therapy provides durable, deep complete remission, and long-term cures in relapsed and refractory B-ALL. However, with this new treatment modality, 10%-30% of patients do not achieve remission, and over 50% experience relapse after therapy. Currently, there are two approved CD19-specific CAR-T cell constructs in B-ALL, Tisagenlecleucel and Brexucabtagene Autoleucel by the United States Food and Drug Administration, and the European Medicines Agency (EMA). In this review, we discuss patients, disease, and CAR-T predictors of outcomes in B-ALL. We describe the two approved CD19-directed CAR-T cell products, review the current literature, and discuss factors associated with high risks of therapy failure and future direction in CAR-T cell therapy for B-ALL.

A rare incidence and management of complex odontoma and surgical dehiscence in maxillary anterior region: A case report.

Odontoma is a benign odontogenic tumour, which is rather considered hamartoma. Hamartoma is not a true neoplasm, rather a growth of abnormal mixture of cells found in the body area they normally grows. Fully developed odontomas generally consist of enamel, dentin and pulpal tissues, in an unorganised manner. Some of them may contain cementum too. These are further grouped into compound and complex, depending on their clinical, radiographic and histologic features. Odontomas are generally asymptomatic and slow growing, but may cause bone expansion and hinderance in tooth eruption. These lesions are generally diagnosed by coincidence in radiograph. We are presenting a case and surgical management of complex odontoma and post-operative dehiscence in the anterior right maxillary region of a 38-year-old male.

Extramedullary Multiple Myeloma: A Patient-Focused Review of the Pathogenesis of Bone Marrow Escape.

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells, predominantly in the bone marrow. The presentation of MM in extramedullary tissue, particularly the liver, is uncommon with only a few reported cases in literature. We report a rare and unusual presentation of kappa light chain restricted MM with progression of disease to involve the liver. MM was initially diagnosed on bone marrow biopsy, initially treated with carfilzomib, lenalidomide and dexamethasone, later changed to bortezomib, daratumumab and dexamethasone. There was subsequent progression with a new biopsy-proven myelomatous liver lesion. The patient could not receive high-dose chemotherapy due to multiple co-morbidities and extent of disease and eventually succumbed to her disease rapidly. This article emphasizes the poor prognosis of extramedullary involvement in MM and the pathogenic mechanisms by which it develops. Based on a review of the literature of other cases and case series of solitary or diffuse myeloma involvement in the liver, high-dose chemotherapy in combination with proteasome inhibitors and immunomodulators has the best success rate with less relapse and progressive disease in extramedullary myeloma. Our analysis concluded that the gain of CD44, loss of CD56, loss of very late antigen-4 (VLA-4), imbalance of the chemokine receptor-4-chemokine ligand-12 (CXCR4-CXCL12) axis, metastasis-associated lung adenocarcinoma 1 (MALAT1) upregulation, RAS pathway activation as well as 13q and 17p deletions show an increased propensity of malignant plasma cells to leave the bone marrow and hone in extramedullary sites giving rise to more aggressive extramedullary diseases. Targeted therapeutics such as CD44v-directed therapy and reactivation of p53 to wild-type conformation could potentially be evaluated as treatment options in the future to improve outcomes in this aggressive form of MM, especially in patients with advanced disease and limited treatment options.

Transcriptome wide identification and characterization of regulatory genes involved in EAA metabolism and validation through expression analysis in different developmental stages of finger millet spikes.

Finger millet is a rich source of seed storage proteins (SSPs). Various regulatory genes play an important role to maintain the quality and accumulation of SSPs in crop seeds. In the present study, nine regulatory genes of EAAs metabolic pathway, i.e., aspartate kinase, homoserine dehydrogenase, threonine synthase, threonine dehydratase, dihydrodipicolinate synthase, cystathionine γ synthase, anthranilate synthase, acetolactate synthase and lysine 2-oxoglutarato reductase/saccharopine dehydrogenase (LOR/SD) were identified from the transcriptomic data of developing spikes of two finger millet genotypes, i.e., GP-45 and GP-1. Results of sequence alignment search and motif/domain analysis showed high similarity of nucleotide sequences of identified regulatory genes with their respective homologs in rice. Results of promoter analysis revealed the presence of various cis-regulatory elements, like nitrogen responsive cis-elements (O2-site and GCN4), light responsive cis-elements, and stress responsive cis-elements. The presence of nine regulatory genes identified from the transcriptomic data of GP-45 and GP-1 was further confirmed by real time expression analysis in high and low protein containing genotypes, i.e., GE-3885 and GE-1437. Results of real time expression analysis showed significantly higher expression (p ≤ 0.01) of regulatory genes in GE-3885 rather than GE-1437 under control and treatment condition. Crude protein content of GE-3885 was found to be significantly higher (p ≤ 0.01) in comparison to GE-1437 under control condition, while under treatment condition GE-1437 was found to be more responsive to KNO3 treatment rather than GE-3885.

Nomogram Identifies Age as the Most Important Predictor of Overall Survival in Oral Cavity Squamous Cell Cancer After Primary Surgery.

Our goal was to determine the most important predictors and construct a nomogram for overall survival (OS) in oral cavity squamous cell cancer (OCSCC) treated with primary surgery followed by observation, adjuvant radiation or chemoradiation. Multivariable analysis was performed using Cox Proportional Hazard model of 9258 OCSCC patients from Surveillance, Epidemiology and End Results Program (SEER) database treated with surgery from 2003 to 2009. Potential predictors of OS were age, gender, race, tobacco use, oral cancer sub-sites, pathologic tumor stage and grade, pathologic nodal stage, extra-capsular invasion, clinical levels IV and V involvement, and adjuvant treatment selection. Weighted propensity scores for treatment were used to balance observed baseline characteristics between three treatment groups in order to reduce bias. Following primary surgery, patients underwent observation (56%), radiation alone (31%) or chemoradiation (13%). All tested predictors were statistically significant and included in our final nomogram. Most important predictor of OS was age, followed by pathologic tumor stage. SEER based-survival nomogram for OCSCC patients differs from published models derived from patients treated in a single or few academic treatment centers. An unexpected finding of patient age being the best OS predictor suggests that this factor may be more critical for the outcome than previously anticipated.

Stevens-Johnson Syndrome: A Perplexing Diagnosis.

Stevens-Johnson syndrome/toxic epidermal necrolysis is a spectrum of mucocutaneous reactions that can occur due to drug reactions, infections with Mycoplasma pneumonia, human immunodeficiency virus (HIV), cancer, and genetics. Stevens-Johnson syndrome involves less than 10% of the body surface, while toxic epidermal necrolysis involves greater than 30%. The most common site of the lesions is mucocutaneous surfaces such as the eyes and oral cavity. Our patient was a 44-year-old female who presented to the emergency department with concerns for pain in her eyes, hands and feet, rash, and sore throat. Her rash worsened during the initial hospitalization. This case emphasizes the importance of pattern recognition of Stevens-Johnson syndrome, as this is a rare but serious condition that must be recognized and treated appropriately. The reaction is most commonly due to medications; however, a thorough history and physical exam are vital to diagnosing this potentially fatal condition.

New superior modified fornix-based twin-site phacotrabeculectomy.

Phacotrabeculectomy is the preferred surgical management of coexisting visually significant cataract and moderate to advanced glaucoma. We report the surgical technique of a new modified fornix-based separate-site phacotrabeculectomy, with mitomycin C (MMC) application, in both primary open angle and angle closure glaucoma. In this new separate-site technique, both phaco and filtration are accommodated superiorly, side by side, hence called twin-site. This was achieved in an efficacious and safe manner with sparing of limbal stem cells without compromising safety. It is not only MMC-compatible but also has a low incidence of wound leak. The technique has no adverse consequence on the survival of the bleb, and we achieved complete success in 79.2% and total success in 93.1% in 130 eyes of 117 patients, in the intermediate term. Furthermore, the time taken for this separate-site surgical technique is comparable to published one-site procedures.

Isolated Laryngeal Amyloidosis Mimicking Laryngeal Cancer.

Amyloidosis is the deposition of an extracellular fibrillar protein in the tissues leading to organ dysfunction. Laryngeal amyloidosis is a rare phenomenon. We report a case of isolated laryngeal amyloidosis which was initially suspicious for laryngeal cancer on magnetic resonance imaging (MRI) but histopathology showed the presence of amyloid. Systemic workup was negative. The patient is being managed conservatively.

A diagnostic challenge: An incidental lung nodule in a 48-year-old nonsmoker.

A 43-year-old female with a medical history of renal stones, hypertension, diabetes mellitus Type 2, and depression presented to her urologist with bilateral flank pain. She complained of worsening exertional dyspnea over the last several months with recent weight gain. She also endorsed night sweats and intermittent, scant hemoptysis over the past year. She denied fever, chills, nausea, vomiting, diarrhea, constipation, hematuria, or excessive joint or muscle pain. Physical examination was unremarkable. Computed tomography scan of abdomen and pelvis demonstrated bilateral nonobstructing renal stones and a 1.8 cm × 1.7 cm nodular opacity in the right lower lobe of the lung, not present on previous scan 1 year prior. Surgical wedge resection was performed and subsequent pathologic examination demonstrated a 1.2 cm × 0.6 cm × 0.5 cm soft, gelatinous well-demarcated mass in the right lower lobe wedge specimen without gross evidence of necrosis or hemorrhage confirming colloid adenocarcinoma of the lung.

Ectopic thyroid: The great mimicker.

Ectopic thyroid tissue is very rare, but its prevalence increases in those with thyroid pathology. It typically occurs due to aberrant development of the thyroid gland during its migration to the pretracheal region. In this report, there are two cases of mediastinal ectopic thyroid tissue discussed, which were initially considered to be malignancies. The hospital course, diagnostic workup, including the use of computed tomography and positron emission tomography scans, and the characteristic features of the tissue are examined here. Due to the imaging characteristics, it is important to consider ectopic thyroid tissue as a differential diagnosis for mediastinal masses as encountered in these cases. Asymptomatic ectopic thyroid tissue is usually treated medically; however, patients in both of our cases opted for surgical resection of the masses even after confirmation of the origin of the tissues.

Assessing the Effect of Weight-Based Protocol Modifications to Lower Dose for CT-Guided Hepatic and Renal Tumor Radiofrequency Ablations.

OBJECTIVE: This study assessed radiation dose after CT-guided percutaneous radiofrequency ablations (RFAs) of hepatic and renal tumors and the effect of weight-based CT protocol modification for lowering overall dose in these procedures. MATERIALS AND METHODS: CT-guided RFA for renal and hepatic ablations performed from January 1, 2009, through December 31, 2009, were retrospectively reviewed (90 men and 48 women; age, 42-81 years). The radiation dose was recorded during each of the following steps: planning, performing, and postprocedure. Weight-based protocol modification changes in tube voltage and tube current were then applied to renal and hepatic ablations performed subsequently (18 men and 11 women; age, 48-82 years). Image quality, needle localization, lesion detection, ability to detect complications, and overall operator satisfaction were noted for each case (score, 1-5). Dose reduction after modification was then calculated. RESULTS: Retrospective analysis found a mean (± SD) overall CT dose index (CTDI) for CT-guided RFA to be 16.5 ± 2.3 mGy. After protocol modification, the mean CTDI decreased to 6.63 ± 0.67 mGy, a 59.6% reduction overall; for hepatic ablations, the reduction was 65.96% (p < 0.0001) and the reduction for renal ablations was 38.97% (p = 0.0153). Image quality analysis showed high operator satisfaction (3-5), including adequate needle localization (4-5), lesion visibility (3-5), and high performer confidence (4-5). Higher dose reduction was noted for patients weighing more than 180 lb (82 kg) (p < 0.0001). CONCLUSION: Simple weight-based CT protocol modifications can significantly reduce radiation dose during CT-guided percutaneous ablations in the liver and kidneys without significantly sacrificing image quality.

Role of Imaging in the Era of Precision Medicine.

Precision medicine is an emerging approach for treating medical disorders, which takes into account individual variability in genetic and environmental factors. Preventive or therapeutic interventions can then be directed to those who will benefit most from targeted interventions, thereby maximizing benefits and minimizing costs and complications. Precision medicine is gaining increasing recognition by clinicians, healthcare systems, pharmaceutical companies, patients, and the government. Imaging plays a critical role in precision medicine including screening, early diagnosis, guiding treatment, evaluating response to therapy, and assessing likelihood of disease recurrence. The Association of University Radiologists Radiology Research Alliance Precision Imaging Task Force convened to explore the current and future role of imaging in the era of precision medicine and summarized its finding in this article. We review the increasingly important role of imaging in various oncological and non-oncological disorders. We also highlight the challenges for radiology in the era of precision medicine.

Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer-related mortality in the United States. Because of the lack of viable treatment options for HCC, prevention in high-risk patients has been proposed as an alternative strategy. The main risk factor for HCC is cirrhosis and several lines of evidence implicate epidermal growth factor (EGF) in the progression of cirrhosis and development of HCC. We therefore examined the effects of the EGF receptor (EGFR) inhibitor erlotinib on liver fibrogenesis and hepatocellular transformation in three different animal models of progressive cirrhosis: a rat model induced by repeated, low-dose injections of diethylnitrosamine (DEN), a mouse model induced by carbon tetrachloride (CCl4 ), and a rat model induced by bile duct ligation (BDL). Erlotinib reduced EGFR phosphorylation in hepatic stellate cells (HSC) and reduced the total number of activated HSC. Erlotinib also decreased hepatocyte proliferation and liver injury. Consistent with all these findings, pharmacological inhibition of EGFR signaling effectively prevented the progression of cirrhosis and regressed fibrosis in some animals. Moreover, by alleviating the underlying liver disease, erlotinib blocked the development of HCC and its therapeutic efficacy could be monitored with a previously reported gene expression signature predictive of HCC risk in human cirrhosis patients. CONCLUSION: These data suggest that EGFR inhibition using Food and Drug Administration-approved inhibitors provides a promising therapeutic approach for reduction of fibrogenesis and prevention of HCC in high-risk cirrhosis patients who can be identified and monitored by gene expression signatures.

Frequency, risk factors, and adverse sequelae of bone loss in patients with ostomy for inflammatory bowel diseases.

BACKGROUND: Bone loss in patients with inflammatory bowel disease (IBD) with ostomy has not been systemically studied. The aims of the study were to evaluate the frequency, risk factors, and sequelae of bone loss in patients with IBD and stomas and to monitor the change in bone mineral density (BMD) over time after ostomy. METHODS: A total of 126 patients met the inclusion criteria (i.e., those with IBD diagnosis and stoma), including ileostomy (N = 120), colostomy (N = 3), and jejunostomy (N = 3). BMD was measured on dual-energy X-ray absorptiometry (DEXA). Patients were classified as having normal or low BMD based on the International Society for Clinical Densitometry criteria. Thirty-two demographic and clinical variables were evaluated with logistic regression models. RESULTS: At a median of 6.6 years (interquartile range, 2-18.7 yr) after stoma, 37 (29.4%) patients had a low BMD. On univariate analysis, there were no significant differences between the normal and low BMD groups in the following variables: gender, race, age at diagnosis of IBD, prevalence of Crohn's disease and ulcerative colitis, age at ostomy, duration from diagnosis to DEXA and from ostomy to DEXA, menopausal age, diabetes, hypothyroidism, renal stones, short bowel syndrome, history of smoking or excessive alcohol use, family history of IBD or osteoporosis, daily calcium and vitamin D supplement, estrogen replacement, and steroid use. Body mass index was significantly lower in the low BMD group than the normal BMD group (23.3 ± 5.5 versus 26.0 ± 5.2, P = 0.013). Fragility fracture occurred in 8 (21.6%) patients in low BMD group and 4 (4.5%) patients in normal BMD group (P = 0.006). In a multivariate analysis, low body mass index was the only covariate-adjusted factor associated with low BMD. In patients with multiple DEXA scans available over time after ostomy, hip BMD was found to improve marginally, and the lumbar and femoral BMD remained stable. CONCLUSIONS: Low BMD was common in patients with IBD after ostomy, largely based on the findings in patients with CD with ileostomy. Fragility fracture was 5 times more frequent in patients with ostomy with low BMD compared with those with normal BMD. The low BMD was associated with a low body mass index. Screening and surveillance of BMD should routinely be performed, particularly in these patients at risk. Bone mass tends to stabilize over time after stoma.

Selective HDAC1/HDAC2 inhibitors induce neuroblastoma differentiation.

While cytotoxic chemotherapy remains the hallmark of cancer treatment, intensive regimens fall short in many malignancies, including high-risk neuroblastoma. One alternative strategy is to therapeutically promote tumor differentiation. We created a gene expression signature to measure neuroblast maturation, adapted it to a high-throughput platform, and screened a diversity oriented synthesis-generated small-molecule library for differentiation inducers. We identified BRD8430, containing a nine-membered lactam, an ortho-amino anilide functionality, and three chiral centers, as a selective class I histone deacetylase (HDAC) inhibitor (HDAC1 > 2 > 3). Further investigation demonstrated that selective HDAC1/HDAC2 inhibition using compounds or RNA interference induced differentiation and decreased viability in neuroblastoma cell lines. Combined treatment with 13-cis retinoic acid augmented these effects and enhanced activation of retinoic acid signaling. Therefore, by applying a chemical genomic screening approach, we identified selective HDAC1/HDAC2 inhibition as a strategy to induce neuroblastoma differentiation.

Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis.

BACKGROUND & AIMS: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.