Association between elevated lactate and clinical outcomes in adults with diabetic ketoacidosis.

PURPOSE: To assess the occurrence of hyperlactatemia among patients admitted to the intensive care unit (ICU) with diabetic ketoacidosis (DKA), and effect on in-hospital mortality. MATERIALS AND METHODS: A retrospective, multicentre, cohort study of adult patients admitted to ICU with a primary diagnosis of DKA in Australia and New Zealand, utilising a pre-existing dataset. The primary exposure variable was lactate, dichotomised into normolactatemia (lactate <2.0 mmol/L) and hyperlactatemia (lactate ≥ 2.0 mmol/L) groups. The primary outcome was in-hospital mortality. Secondary outcomes included ICU and hospital length of stay (LOS), requirement for ventilation, renal replacement therapy (RRT) and inotropes. RESULTS: The final dataset included 9061 patients. Hyperlactatemia was associated with in-hospital mortality (Odds Ratio [OR] 1.785 (95% CI 1.122-2.841, p = 0.014), hospital LOS (Geometric mean ratio [GMR] 1.063, 95% CI 1.025-1.103, p = 0.001), ICU LOS (GMR 1.057, 95% CI 1.026-1.09. p < 0.001), RRT (OR 2.198, 95% CI 1.449-3.334, p < 0.001) and inotropes (OR 1.578, 95% CI 1.311-1.899, p < 0.001). These associations persisted in Type 2 but not Type 1 diabetics. CONCLUSIONS: Hyperlactatemia in patients admitted to ICU with DKA is associated with higher mortality, longer hospital and ICU LOS, and higher rates of mechanical ventilation, RRT and inotropes.

Efficacy of extracorporeal shockwave lithotripsy with furosemide and hydration in renal stone management: A randomised controlled trial.

Objective: To assess the effect of diuretics (furosemide) administered before extracorporeal shockwave lithotripsy (ESWL) followed by continuous infusion of 0.9% NaCl during the ESWL in patients with renal stones. Patients and methods: A tertiary care teaching hospital-based prospective randomised controlled trial was conducted from July 2015 to June 2017, including 714 patients who underwent ESWL. The patients were randomised in two groups: in Group-A, patients received 40 mg furosemide 30 min before each ESWL session and 1000 mL 0.9% NaCl intravenous hydration during the procedure. In Group-B, the patients only received 0.9% NaCl. All patients were followed-up every 2 weeks for 3 months with X-ray and ultrasonography of the kidney, ureter and bladder. Patients without a radio-opaque stone at follow-up were classified as successes. Results: After 2 months, the stone-free rate (SFR) was much higher in Group-A, at 77.0% vs 65.3% (P < 0.001). Further, for patients aged ≤40 years, the SFR was significantly higher in Group-A than Group-B, at 89.2% vs 71.4% (P < 0.001). The mean (SD) age of the patients was 34.4 (8.23) years. Amongst them, 441 (61.8%) were male and 273 (38.2%) were female. The mean (SD) stone size was 1.42 (0.21) cm in Group-A and 1.40 (0.20) cm in Group-B. Conclusion: We conclude that the efficacy of diuretics (furosemide) along with hydration is superior to hydration alone during ESWL for renal stone clearance. Abbreviations: BMI: body mass index; KUB: kidney, ureter and bladder; OPD: Outpatient Department; ESWL: extracorporeal shockwave lithotripsy; SFR, stone-free rate.

A Single Institution Retrospective Comparison Study of Locoregional Recurrence After Accelerated Partial Breast Irradiation Using External Beam Fractionation Compared with Whole Breast Irradiation with 8 Years of Follow-Up.

BACKGROUND: Accelerated partial breast irradiation (APBI) was developed to address disadvantages of overall treatment time and potentially unnecessary radiation associated with whole breast irradiation (WBI). We report updated results of our single institution study using an external beam APBI regimen with a median follow-up of 8 years. METHODS: A total of 290 APBI patients with AJCC Stage 0-II breast cancer were compared with 290 WBI patients with matched tumor characteristics. Toxicities were scored based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Cox regression models were used to predict likelihood of freedom from ipsilateral failure. RESULTS: Median follow-up was 8 years in the APBI group and 7.5 years in the WBI group. In the APBI group, there were 18 (6.2%) ipsilateral breast tumor recurrence (IBTR), 13 (72%) had elsewhere failures (EF), and 5 (28%) had local failures (LF) with a median time to failure of 64.1 months. In the WBI group, there were three (1.0%) IBTR; one (33%) was an EF and two (67%) were LF with a median time to failure of 91 months. APBI was 4.6 times more likely (hazard ratio 4.57, 95% confidence interval 1.3-16.2, p = 0.02) to have an IBTR than WBI after adjusting for age, tumor size, histology, grade, and estrogen receptor status. Fatigue, erythema, and desquamation toxicities were significantly less in the APBI group then the WBI group. CONCLUSIONS: IBTR rates were higher in external beam APBI group compared with WBI, but APBI had fewer toxicities. Clinicians must weigh the risks and benefits of APBI when making a recommendation for partial breast irradiation after lumpectomy.

Targeting pathways mediating resistance to anti-EGFR therapy in squamous cell carcinoma of the head and neck.

INTRODUCTION: As epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of squamous cell carcinomas of the head and neck (SCCHN), several therapeutic agents that target EGFR have been evaluated for the treatment of SCCHN. Although patients with SCCHN derive clinical benefit from anti-EGFR agents, most notably the EGFR monoclonal antibody cetuximab, these patients eventually become resistant to EGFR-based therapies; preclinical studies have shown activation of secondary signaling pathways that lead to resistance to EGFR inhibition and, as such, serve as potential therapeutic targets to overcome resistance to EGFR inhibitors. AREAS COVERED: This review summarizes the results of recently completed trials of anti-EGFR agents in SCCHN, highlights the various mechanisms that drive resistance to EGFR inhibitors in SCCHN, and focuses on several novel targeted agents that could potentially help overcome resistance to EGFR-based therapies in SCCHN. Expert commentary: Due to the development of resistance to EGFR-targeted therapies, novel treatment approaches to overcome resistance are a key unmet need for SCCHN.

Utilization of accelerated partial breast irradiation for ductal carcinoma in situ, 2003-2011: report from the national cancer database.

BACKGROUND: Data on recent trends and correlates of utilization for accelerated partial breast irradiation using brachytherapy (APBI-b) for ductal carcinoma in situ (DCIS) are lacking. METHODS: This study included 113,841 DCIS patients from the National Cancer Data Base, of whom 8,709 (6.5 %) underwent APBI-b and 105,132 (93.5 %) underwent external beam irradiation after lumpectomy between 2003 and 2011. Trends in APBI-b use, American Society for Radiation Oncology (ASTRO) guideline concordance, and independent factors related to APBI-b use were examined. RESULTS: APBI-b use increased from 1.6 % in 2003 to 11.9 % in 2008 and then decreased to 9.1 % in 2011 (p < 0.001). Before 2009, 24.6 % of patients undergoing APBI-b were in the ASTRO guideline 'unsuitable' category, but this proportion decreased to 14.6 % after 2009 (p < 0.001). When adjusting for year of diagnosis, patient, tumor, and facility factors, the four strongest independent factors for APBI-b use were year of diagnosis followed by facility location, facility volume, and facility type. APBI-b use was highest in the East South Central census region (13.1 %) and lowest in the New England region (2.0 %). A statistically significant interaction was identified between facility type and volume. Patients in community cancer programs of large volume were more likely to receive APBI-b, whereas patients in larger academic programs were less likely to receive APBI-b. CONCLUSION: APBI-b for DCIS decreased from 2008 to 2011. After year of diagnosis, facility factors were most strongly associated with APBI-b use as opposed to patient and tumor factors. Reasons for these trends are multifactorial and deserve further study.

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. Part II: multidisciplinary management.

Biliary tract cancers (gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases.

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. Part I: diagnosis-clinical staging and pathology.

Biliary tract cancers (gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma, and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases.

Accelerated partial breast irradiation using once-daily fractionation: analysis of 312 cases with four years median follow-up.

BACKGROUND: There are limited data on accelerated partial breast irradiation (APBI) using external beam techniques. Moreover, there are recent reports of increased fibrosis and unacceptable cosmesis with APBI using external beam with BID fractionation. We adopted a once daily regimen of APBI with fractionation similar to that shown to be effective in a Canadian randomized trial of whole breast irradiation. It is unclear whether patients with DCIS or invasive lobular carcinoma (ILC) are suitable for APBI. METHODS: The retrospective cohort included 310 patients with 312 tumors of T1-T2N0-N1micM0 invasive ductal carcinoma (IDC), ILC, or Tis (DCIS) treated with APBI via external beam. Most patients were treated using IMRT with 16 daily fractions of 270 cGy to a dose of 4320 cGy. The target volume included the lumpectomy cavity plus 1.0 cm to account for microscopic disease and an additional 0.5 to 1.0 cm for setup uncertainty and breathing motion. Ipsilateral breast failure (IBF) was pathologically confirmed as a local failure (LF) or an elsewhere failure (EF). RESULTS: Median follow-up was 49 months. Among the 312 cases, 213 were IDC, 31 ILC, and 68 DCIS. Median tumor size was 1.0 cm. There were 9 IBFs (2.9%) including 5 LFs and 4 EFs. The IBF rates among patients with IDC, ILC, and DCIS were 2.4%, 3.2%, and 4.4%, respectively, with no significant difference between histologies. When patients were analyzed by the ASTRO APBI consensus statement risk groups, 32% of treated cases were considered suitable, 50% cautionary, and 18% unsuitable. The IBF rates among suitable, cautionary, and unsuitable patients were 4.0%, 2.6%, and 1.8%, respectively, with no significant difference between risk groups. Acute skin reactions were rare and long-term cosmetic outcome was very good to excellent. CONCLUSIONS: External beam APBI with once daily fractionation has a low rate of IBF consistent with other published APBI studies. The ASTRO risk stratification did not differentiate a subset of patients with a higher rate of IBF. APBI may be an appropriate treatment for women with DCIS and ILC.

Electrochemically intercalated indium-tin-oxide/poly(3-hexylthiophene): A solid-state heterojunction solar cell.

A heterojunction solar cell design composed of poly(3-hexylthiophene) (P3HT) and intercalated indium-tin-oxide (ITO) donor-acceptor system is explored for the first time. Substantial change in band edge of ITO is noticed after intercalation. Structural and surface morphological studies are reported. Due to tuned band gap of ITO, an increase in short circuit current from 0.0012 to 0.46 mA/cm(2), fill factor from 0.39 to 0.51, and power conversion efficiency from 0.000 367 to 0.3% is obtained for heterojunction solar cell when compared to P3HT alone. This novel, room temperature design approach would be of great scientific interest in current solid-state solar cell scenario.

An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer.

Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.

Chemotherapy and high dose radiotherapy followed by resection for locally advanced nonsmall cell lung cancers.

OBJECTIVES: For locally advanced but technically operable nonsmall cell lung cancer (NSCLC), neoadjuvant chemoradiotherapy is frequently used. Ideal radiotherapy dose in this context is unclear. MATERIALS AND METHODS: Twenty-six NSCLC patients with N2 disease were retrospectively reviewed. All received preoperative concurrent platinum-based chemoradiotherapy. Gross tumor volumes received a median of 58 Gy (range, 50-60 Gy). RESULTS: Two patients experienced major complications and died, resulting in a postoperative mortality rate of 7.7%. Three patients (11.5%) had minor complications. Pathologic specimens revealed downstaging in 76.9% of patients. The pathologic complete response (CR) rate was 34.6%. Downstaging of nodes was observed in 20 of 26 patients. With a median follow-up of 18.3 months, the 1- and 3-year actuarial survival rates were 80.2% and 45.7%, respectively. The 1- and 3-year actuarial disease-free survival (DFS) rates were 76.9% and 37.3%, respectively. Patients experiencing mediastinal downstaging had better DFS rates, relative to patients that did not (18-month DFS = 79.2% vs. 0%; P = 0.0001). Differences in RT dose (50-60 Gy) and types of chemotherapeutic regimens did not significantly impact pathologic downstaging rates, CR rates, DFS, or survival. DISCUSSION: Neoadjuvant chemotherapy with high-dose concurrent RT is well tolerated and results in favorable outcomes.

DNA base-excision repair enzyme apurinic/apyrimidinic endonuclease/redox factor-1 is increased and competent in the brain and spinal cord of individuals with amyotrophic lateral sclerosis.

Motor neurons degenerate in amyotrophic lateral sclerosis (ALS). The mechanisms for this neuronal cell death are not known, although apoptosis has been implicated. Oxidative damage to DNA and activation of p53 has been identified directly in motor neurons in cases of ALS. We evaluated whether motor neuron degeneration in ALS is associated with changes in the levels and function of the multifunctional protein apurinic/apyrimidinic endonuclease (APE/Ref-1). APE/Ref-1 functions as an enzyme in the DNA base-excision repair pathway and as a redox-regulation protein for transcription factors. The protein level and localization of APE/Ref-1 are changed in ALS. Immunoblotting showed that APE/Ref-1 protein levels are increased in selectively vulnerable central nervous system (CNS) regions in individuals with ALS compared to age-matched controls. Plasmid DNA repair assay demonstrated that APE from individuals with ALS is competent in repairing apurinic (AP) sites. DNA repair function in nuclear fractions is increased significantly in ALS motor cortex and spinal cord. Immunocytochemistry and single-cell densitometry revealed that APE/Ref-1 is expressed at lower levels in control motor neurons than in ALS motor neurons, which are decreased in number by 42% in motor cortex. APE/Ref-1 is increased in the nucleus of remaining upper motor neurons in ALS, which show a 38% loss of nuclear area. APE-Ref-1 is also upregulated in astrocytes in spinal cord white matter pathways in familial ALS. We conclude that mechanisms for DNA repair are activated in ALS, supporting the possibility that DNA damage is an upstream mechanism for motor neuron degeneration in this disease.

Diverticulitis presenting as a strangulated inguinal hernia.

BACKGROUND/AIM: Inguinal hernia is a common diagnosis for patients presenting with a painful groin mass; other potentially dangerous diagnoses may mimic a groin hernia. We present 3 unusual cases of diverticulitis with perforation. The resulting abscess presented clinically as an atypical strangulated inguinal hernia. METHODS/RESULTS: From July 1, 1999, to June 30, 2000, 344 patients were admitted to the Johns Hopkins Bayview Medical Center with the diagnosis of diverticulitis. Of these patients, 44 (12.8%) required surgical intervention. We report here 3 cases in that academic year of diverticulitis complicated by perforation and abscess formation that presented as atypical strangulated inguinal hernias. In addition to being rare and difficult to diagnose, such cases illustrate that a tender inguinal mass may not represent a hernia. CONCLUSIONS: The diagnosis of strangulated inguinal hernias remains primarily one of clinical suspicion. Radiologic and laboratory studies should augment, not replace, one's clinical diagnosis. In addition, the differential diagnosis of inguinal masses is discussed.