Burkitt lymphoma in the modern era: real-world outcomes and prognostication across 30 US cancer centers.

We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P < .001) and without difference based on setting of administration (ie, inpatient vs outpatient). Outcomes were also improved at an academic vs community cancer center (3-year PFS, 67% vs 46%, P = .006; OS, 72% vs 53%, P = .01). In multivariate models, age ≥ 40 years (PFS, hazard ratio [HR] = 1.70, P = .001; OS, HR = 2.09, P < .001), ECOG PS 2 to 4 (PFS, HR = 1.60, P < .001; OS, HR = 1.74, P = .003), lactate dehydrogenase > 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates.

Impact of conditioning regimen intensity on the outcomes of peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma patients undergoing allogeneic transplant.

There have been no large studies comparing reduced-intensity/non-myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T-cell non-Hodgkin lymphoma (T-NHL) patients undergoing allogeneic transplant (allo-HCT). A total of 803 adults with peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma (age 18-65 years), undergoing allo-HCT between 2008-2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation-specific comorbidity index (HCT-CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79-1.29; p = 0.95). Similarly, non-relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61-1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98-1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92-1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3-4 acute graft-versus-host disease (HR = 0.67; 95% CI = 0.46-0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo-HCT for T-cell NHL.

Allogeneic haematopoietic cell transplantation for myelofibrosis: a real-life perspective.

Myelofibrosis (MF) is a clonal stem cell neoplasm with heterogeneous clinical phenotypes and well-established molecular drivers. Allogeneic haematopoietic stem cell transplantation (HSCT) offers an important curative treatment option for primary MF and post-essential thrombocythaemia/polycythaemia vera MF or secondary MF. With a disease course that varies from indolent to highly progressive, we are now able to stratify risk of mortality through various tools including patient-related clinical characteristics as well as molecular genetic profile. Owing to the high risk of mortality and morbidity associated with HSCT for patients with myelofibrosis, it is important to improve patient selection for transplant. Our primary goal is to comprehensively define our understanding of current practices including the role of Janus Kinase (JAK) inhibitors, to present the data behind transplantation before and after leukaemic transformation, and to introduce novel personalization of MF treatment with a proposed clinical-molecular prognostic model to help elucidate a timepoint optimal for consideration of HSCT.

Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study.

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.

Impact of initial chemotherapy regimen on outcomes for patients with double-expressor lymphoma: A multi-center analysis.

Diffuse large B-cell lymphoma featuring overexpression of MYC and B-Cell Lymphoma 2 (double expressor lymphoma, DEL) is associated with poor outcomes. Existing evidence suggesting improved outcomes for DEL with the use of more intensive regimens than R-CHOP is restricted to younger patients and based on limited evidence from low patient numbers. We retrospectively evaluated the impact of intensive frontline regimens versus R-CHOP in a multicenter analysis across 7 academic medical centers in the United States. We collected 90 cases of DEL, 46 out of 90 patients (51%) received R-CHOP and 44/90 (49%) received an intensive regimen, which was predominantly DA-EPOCH-R. Treatment cohorts were evenly balanced for demographics and disease characteristics, though the intensive group had a higher lactate dehydrogenase (LDH, 326 vs. 230 U/L p = 0.06) and presence of B-symptoms (50% vs. 22%, p = 0.01) compared to the R-CHOP cohort. There was no difference in PFS (median 53 vs. 38 months, p = 0.49) or overall survival (67 vs. not reached months, p = 0.14) between the R-CHOP and intensive therapy cohorts, respectively. On multivariate analysis, intensive therapy was associated with a hazard ratio of 2.35 (95% CI 0.74-7.41), though this was not statistically significant. Additionally, a subgroup analysis of intermediate high-risk lymphoma defined by IPI ≥3 did not identify a difference in survival outcomes between regimens. We conclude that in our multi-center cohort there is no evidence supporting the use of intensive regimens over R-CHOP, suggesting that R-CHOP remains the standard of care for treating DEL.

Surveillance Imaging after Autologous Hematopoietic Cell Transplantation Predicts Survival in Patients with Diffuse Large B Cell Lymphoma.

The utility of surveillance imaging after autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory diffuse large B cell lymphoma (DLBCL) remains unclear. The purpose of this study was to determine whether surveillance imaging predicts survival after AHCT. At the University of Minnesota, serial imaging for early relapse detection has been used prospectively for all consecutive AHCT recipients treated since 2010. The present analysis included 91 AHCT recipients with DLBCL who underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scan at day +100 post-AHCT. 18F-FDG-PET parameters included the Deauville (D) 5-point scale, peak standardized uptake values (SUVmax), total legion glycolysis (TLG), and total metabolic tumor volume (TMTV). Survival of patients with clinically symptomatic versus asymptomatic radiographically detected relapsed DLBCL after AHCT was compared. Sixty patients experienced relapse; 35% was detected on day +100 surveillance PET scan. 5-year overall survival (OS) by 18F-FDG-PET scan at day +100 post-AHCT was significantly lower in D4 and D5 patients (37%; 95% confidence interval [CI], 14% to 100% versus 25%; 95% CI, 43% to 89%) compared with patients with D1 and D2 (62%; 95% CI, 43% to 89% versus 62%; 95% CI, 46% to 84%). TLG and TMTV were not prognostic. SUVmax at day +100 varied from 1.5 (D1) to 17.9 (D5). In multivariate analysis, only SUVmax was predictive of relapse and OS; mortality increased 1.8-fold with each SUVmax doubling (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.3; P < .01). At a median follow-up of 3.3 years (range, 1 to 12 years), lymphoma-related mortality was 1.8-fold higher among patients whose relapse was detected clinically (symptomatic) versus radiographically on surveillance scan (HR, 1.8; 95% CI, .9 to 3.4; P = .08). In patients with relapsed/refractory DLBCL, a routine PET imaging at day +100 post-AHCT detects asymptomatic relapse and high SUVmax identifies patients with poor expected survival of less than 1 year. Identifying this high-risk cohort can potentially highlight patients who might benefit from preemptive interventions to prevent or delay relapse.

Long-term Outcome After Doxorubicin and Ifosfamide Overdose in a Patient With Osteosarcoma and BARD1 Mutation.

Current treatment of high-grade osteosarcoma consists of preoperative chemotherapy, typically using some combination of doxorubicin, cisplatin, ifosfamide, and/or high-dose methotrexate followed by surgical resection. In this report, we present a case of a 21-year-old woman with high-grade osteosarcoma of the chest wall who received 5 times the planned dose of doxorubin and 4 times the planned dose of ifosfamide. She survived this chemotherapy overdose after administration of dimethyl sulfoxide and phenobarbital. Despite the administration of 5 times the proposed dose of doxorubicin, the patient survived without cardiotoxicity, and later delivered a normal baby. Although there are many studies evaluating treatment for chemotherapy regimen-related toxicity, sparse data exist with respect to chemotherapy overdose and the appropriate course of action. This case further confirms the lower cardiotoxicity of continuous intravenous infusion of doxorubicin and provides support for the use of dimethyl sulfoxide in the prevention of toxicity in chemotherapy overdose.

Immune-Mediated Complications after Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) has an integral role in the treatment of malignant and nonmalignant diseases. Long-term complications after HSCT have been well established and include graft-versus-host disease (GVHD), conditioning regimen-related toxicities, disease relapse, and infections. Immune-mediated phenomena are increasingly described after HSCT with clinically significant sequelae. Diagnosis is challenging because of features that overlap with other commonly reported post-transplantation complications. Patients who experience immune-mediated disease after HSCT tend to have poor outcomes. Early recognition of immune-mediated complications is imperative to reduce preventable morbidity and mortality. This review looks at the currently available literature on pathogenesis, incidence, risk factors, treatment, and outcomes of immune-mediated disease (other than GVHD) after HSCT.

Decision-Making Regarding Perioperative Therapy in Individuals with Localized Pancreatic Adenocarcinoma.

Pancreatic cancer is a fatal malignancy that is projected to emerge as the second leading cause of cancer-related death in the United States. Despite the critical advances in surgical strategies, radiographic techniques, and systemic therapy, the treatment modality has remained largely unchanged over the past two decades eliciting a dire need for clinical trials in improving quality of life and prolonging survival in this patient population. Emergence of innovative strategies including novel combination chemotherapy, immunotherapy, vaccines, small compound drugs, among others is avenues under investigation to improve perioperative outcomes in localized pancreatic cancer.

COVID-19 Vaccines and Immunosuppressed Patients With Cancer: Critical Considerations.

BACKGROUND:  Patients with cancer are highly vulnerable to COVID-19 because of immunosuppression from diseases and treatments. Emerging data characterize the impact of COVID-19 vaccines related to cancer malignancies and treatments. OBJECTIVES:  This article provides a clinical foundation on the immune response to the COVID-19 vaccine associated with the impact of cancer and its related treatments. It reviews strategies for vaccine scheduling, Centers for Disease Control and Prevention recommendations, and nursing considerations when administering the vaccine to immunosuppressed patients. METHODS:  Research studies about immune responses to COVID-19 vaccines among immunosuppressed patients with hematologic and solid tumor malignancies were summarized. FINDINGS:  Studies about the humoral immune responses of patients with cancer to COVID-19 vaccines help guide vaccination planning for this population. Critical nursing considerations for patients with cancer receiving COVID-19 vaccination are integral to the provision of optimal clinical oncology care during the pandemic.

Mantle cell lymphoma management trends and novel agents: where are we going?

The heterogeneity in disease pathology, the unpredictability in disease prognosis, and the variability in response to therapy make mantle cell lymphoma (MCL) a focus of novel therapeutic development. MCL is characterized by dysregulated expression of cyclin D1 through a chromosome t(11;14) translocation. MCL international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation status are currently utilized for prognostication. With advances in pharmacokinetic analysis and drug discovery, treatment strategy has evolved from chemotherapy to combination of targeted, epigenetic, and immune therapies. In this review, we discuss investigational and newly approved treatment approaches. In a short time, the US Food and Drug Administration (FDA) has approved five agents for the treatment of MCL: lenalidomide, an immunomodulatory agent; bortezomib, a proteasome inhibitor; and ibrutinib, acalabrutinib, and zanubrutinib, all Bruton kinase inhibitors. Epigenetic agents (e.g. cladribine and vorinostat), mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus and everolimus), and monoclonal antibodies and/or antibody-drug conjugates (e.g. obinutuzumab, polatuzumab, and ublituximab) are promising therapeutic agents currently under clinical trial investigation. Most recently, chimeric antigen receptor (CAR)-T cell therapy and bispecific T-cell engager (BiTE) therapy even open a new venue for MCL treatment. However, due to its intricate pathology nature and high relapse incidence, there are still unmet needs in developing optimal therapeutic strategies for both frontline and relapsed/refractory settings. The ultimate goal is to develop innovative personalized combination therapy approaches for the purpose of delivering precision medicine to cure this disease.

Nutritional Supplements and Complementary/Alternative Medications in Patients With Hematologic Diseases and Hematopoietic Stem Cell Transplantation.

This perspective article discusses the various practices classified as complementary and alternative medicine (CAM) and reviews the benefits and uncertainties with respect to nutritional supplements in patients with hematological disease. It considers the high prevalence of CAM use especially among cancer survivors, particularly patients with hematologic malignancies and allogeneic stem cell transplant survivors, many of whom believe (because of extensive advertising) that supplements are anticancer/antitoxic agents, despite the paucity of evidence to support any benefit and the enormous cost to the individual. CAM constitutes various practices and nutritional behaviors including prayers, relaxation, spiritual healing, nutritional supplements, meditation, religious counseling, massage, and support groups. We highlighted the current literature regarding CAM practices and focused our discussion on the omnipresent nutritional supplements in particular to further expound on their benefits and adverse effects. As the number of survivors after HSCT increases over the next several years along with prevalence of CAM use, it becomes imperative to ascertain any beneficial potential, as well as toxicities associated with CAM use in this population.

New targets for CAR T therapy in hematologic malignancies.

As we expand our acumen of the intricacies of hematological malignancies at a genetic and cellular level, we have paved the way in advancing novel targeted therapeutic avenues such as chimeric antigen receptor T-cell therapies (CAR T). Engineering cells to target a specific antigen has led to dramatic remission rates in cases of relapsed/refractory non-Hodgkin lymphoma, acute lymphoblastic leukemia as well as multiple myeloma thus far with trials in place to further advance targeted therapies in other hematological malignancies. Most currently available CAR T therapies target CD19 antigen. Studies are underway exploring novel CAR T products aimed at other tumor-specific antigens with potential to improve the efficacy and reduce the toxicities. Early studies have confirmed safety and efficacy of CD22 and BCMA targeted CAR T therapies. Moreover, various other targets including CD20, CD30, CD123, kappa, and lambda light chains among others are under clinical investigation as potential avenues of targeted therapy. This review highlights the shift in the treatment paradigm in pursuing diverse antigen targets while addressing the challenges in terms of the efficacy and toxicity of current CAR T-cell therapies.

Immunotherapy Approaches in HPV-Associated Head and Neck Cancer.

Immunotherapy approaches for head and neck squamous cell carcinoma (HNSCC) are rapidly advancing. Human papillomavirus (HPV) has been identified as a causative agent in a subset of oropharyngeal cancers (OPC). HPV-positive OPC comprises a distinct clinical and pathologic disease entity and has a unique immunophenotype. Immunotherapy with anti-PD1 checkpoint inhibitors has exhibited improved outcomes for patients with advanced HNSCC, irrespective of HPV status. To date, the clinical management of HPV-positive HNSCC and HPV-negative HNSCC has been identical, despite differences in the tumor antigens, immune microenvironment, and immune signatures of these two biologically distinct tumor types. Numerous clinical trials are underway to further refine the application of immunotherapy and develop new immunotherapy approaches. The aim of this review is to highlight the developing role of immunotherapy in HPV-positive HNSCC along with the clinical evidence and preclinical scientific rationale behind emerging therapeutic approaches, with emphasis on promising HPV-specific immune activators that exploit the universal presence of foreign, non-self tumor antigens.

Pegylated liposomal doxorubicin-induced renal toxicity in retroperitoneal liposarcoma: a case report and literature review.

Doxorubicin is one of the most active drugs for sarcoma. Pegylated liposomal doxorubicin (PLD) is a unique formulation of doxorubicin, which carries a more favorable toxicity profile in comparison with free doxorubicin. The main toxicity of PLD is hand-foot syndrome. Unlike free doxorubicin, PLD is unlikely to cause alopecia, nausea, myelosuppression, or cardiotoxicity. Additionally, no premedications are required. We describe the case of a 50-year-old man with advanced retroperitoneal liposarcoma who developed irreversible PLD-associated progressive renal failure requiring chronic hemodialysis due to a thrombotic microangiopathy. No cardiotoxicity was noted 84 months after he initiated PLD. This case describes a lesser known toxicity of PLD and may be a toxicity of long-term treatment with other liposomal drugs.

Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies.

Hodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody-drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field.

Long-term cure of soft tissue sarcoma with pegylated-liposomal doxorubicin after doxorubicin and ifosfamide failure.

BACKGROUND: Doxorubicin is one of the most active drugs available for the treatment of sarcoma. Pegylated-liposomal doxorubicin (PLD) is a formulation of doxorubicin in which the doxorubicin is encapsulated in liposomes coated with methoxypoly (ethylene glycol); this formulation results in decreased uptake by the reticuloendothelial system, higher concentrations of drug in tumor, and less toxicity, including reduced cardiotoxicity, nausea, alopecia, and myelosuppression. No premedication is necessary. While PLD has a better toxicity profile than free doxorubicin, there is no consensus on the relative efficacy of PLD and free doxorubicin in sarcoma. CASE PRESENTATION: In this report, we describe a patient with high-grade metastatic soft tissue sarcoma with rapid recurrence after adjuvant treatment with free doxorubicin, cisplatin, ifosfamide, and dacarbazine. Second-line treatment with PLD resulted in long-term disease remission during a 20-year follow-up period. Mucositis and hand-foot syndrome were controlled by adjustment of dose and treatment interval. CONCLUSIONS: This case illustrates the curative potential of PLD after failure of free doxorubicin and the absence of long term cardiotoxicity with PLD. As with all drugs, individual adjustment of dose and treatment interval is important.

Characteristics and outcomes of very low birth weight infants receiving epinephrine during delivery room resuscitation.

BACKGROUND: Delivery room resuscitation of very low birth weight infants can involve use of endotracheal or intravenous epinephrine. Data of the past 19 years were reviewed to identify the usage of epinephrine in delivery room and identify characteristics of these babies. METHODS: Neonates with ≤1500g birthweight from January 1996 to August 2014 were reviewed. Infants born alive and admitted to NICU were eligible. Characteristics such as demographics, survival and outcomes were recorded. Variables significant at p≤0.1 among neonates receiving epinephrine were further analyzed via multiple logistic regressions. RESULTS: Out of 5868 eligible neonates, 416 (7%) received epinephrine in the delivery room. The infants who received epinephrine were of lower estimated gestational age (25 vs. 28wk) and lower birth weight (746 vs. 980g). Gender, race and mode of delivery were comparable between the two cohorts. Survival was higher in non-epinephrine group (89.4 vs. 61.1%). Bacterial infection (24.3 vs. 18.4%) and combined grade 3 and 4 intraventricular hemorrhage (18.4 vs. 8.4%) were higher in epinephrine group. Use of epinephrine in the delivery room was associated with decreased survival even after controlling for birth weight, gestational age and low Apgar scores [Odd ratio - 0.48 with 95% CI (0.37-0.62), p<0.001]. CONCLUSION: Neonates with lower birth weight and younger gestational age were more likely to receive epinephrine during resuscitation at birth. Use of epinephrine in delivery room was associated with lower survival and severe intraventricular hemorrhage among very low birth weight infants.

Methimazole-induced insulin autoimmune syndrome.

BACKGROUND: Hypoglycemia in a critical care setting is often multifactorial with iatrogenic insulin use, sulfonylurea (SU) use, sepsis, adrenal insufficiency and insulinoma among the common causes. Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the presence of insulin-binding autoantibodies to the sulfhydryl group-containing agents. We report a case of methimazole-induced IAS managed in the intensive care unit. CASE PRESENTATION: A 76-year-old woman with a history of primary hyperthyroidism was sent from a nursing home for unresponsiveness. Vital signs were significant for hypotension (74/46) and low blood sugars. Fluid resuscitations with normal saline and 50% dextrose stabilized the blood pressure (BP) to 135/75 and her blood glucose to 264. Due to respiratory distress and septic appearance, she required emergency intubation. Nursing home medications were noted for methimazole and absence of any insulin or SU use. Empiric antibiotic treatment was started and fluid resuscitation was continued while home medications were held. Her laboratory values were significant for elevated creatinine, lactic acid, serum cortisol, C-peptide, and insulin. Her cultures, SU screen and computerized tomography (CT) scan were negative for significant findings. On day 2, in addition to 10% dextrose, octreotide was initiated for recurrent hypoglycemia. Her blood glucose (BG) continued to drop throughout the day for which she required glucagon support and a D20 infusion. By day 4, the rate of infusion was titrated up and her BG continued to drop to <60 mg/dl despite D20, octreotide and tube feeds with concentrated calories (1.5 cal/ml). Due to her declining health, her family endorsed palliative care and she was extubated. After day 11, her hypoglycemic episodes resolved and she remained endogenously euglycemic. CONCLUSIONS: IAS is associated with methimazole use due to formation of autoantibodies to insulin after its interaction with Sulfhydryl (SH) group in methimazole. While IAS is a rare entity, it demands consideration in hypoglycemia in patients with autoimmune conditions.

Sonic hedgehog pathway expression in non-small cell lung cancer.

OBJECTIVE: Activation of the hedgehog pathway is an important signaling mechanism crucial in embryogenesis and has strong links to carcinogenesis. This study investigates the expression of the Sonic hedgehog pathway molecules in non-small cell lung tumors as it relates to clinical outcome of various non-small cell lung cancers. METHODS: A tissue microarray with 81 samples from 42 patients with various non-small cell lung cancer histologies was examined without the aid of laser microdissection. All samples were stained with antibodies directed against Sonic hedgehog, Ptch-1, Smoothened, and Gli-1. RESULTS: Most of the tumor samples showed negative to weak expression of the pathway proteins (Sonic hedgehog, 38% negative to 20% weak; Ptch-1, 100% negative; Smoothened, 69% negative to 7% weak; Gli-1, 57% negative to 5% weak) compared with higher expression in normal lung epithelial cells. CONCLUSION: The same pathway expression did not correlate with clinical outcome. While our results do not provide any indication that the pathway molecules are correlated to overall patient survival possibly due to the limited sample size, our study shows minimum overexpression of Sonic hedgehog pathway in non-small cell lung cancer and this did not correlate clinically with patient outcome.