Based on our previous work on the clinical activity of cetuximab in recurrent nasopharyngeal carcinoma (NPC), we evaluated the feasibility of adding cetuximab to concurrent cisplatin and ...intensity-modulated radiotherapy (IMRT) in locoregionally advanced NPC.
Patients with American Joint Committee on Cancer stage III–IVB NPC were given an initial dose of cetuximab (400 mg/m2) 7–10 days before receiving concurrent IMRT, weekly cisplatin (30 mg/m2/week) and cetuximab (250 mg/m2/week).
Thirty patients (median age of 45 years) with stage III (67%), IVA (30%) and IVB (3%) nonkeratinizing NPC were enrolled. Grade 3–4 oropharyngeal mucositis occurred in 26 (87%) patients and 10 (33%) patients required short-term nasogastric feeding. Grade 3 radiotherapy-related dermatitis occurred in six patients (20%) and three patients (10%) had grade 3 cetuximab-related acneiform rash. These grade 3–4 skin and mucosal toxic effects were manageable and reversible. At a median follow-up of 31.8 months 95% confidence interval (CI) 26.2–32.1 months, the 2-year progression-free survival was 86.5% (95% CI 74.3% to 98.8%).
Concurrent administration of cetuximab, weekly cisplatin and IMRT is a feasible strategy against locoregionally advanced NPC. Preliminary survival data compare favorably with historic data and further follow-up is warranted.
This randomized trial compared the rates of delayed xerostomia between two-dimensional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in the treatment of early-stage ...nasopharyngeal carcinoma (NPC).
Between November 2001 and December 2003, 60 patients with T1-2bN0-1M0 NPC were randomly assigned to receive either IMRT or 2DRT. Primary end point was incidence of observer-rated severe xerostomia at 1 year after treatment based on Radiotherapy Oncology Group /European Organisation for the Research and Treatment of Cancer late radiation morbidity scoring criteria. Parallel assessment with patient-reported outcome, stimulated parotid flow rate (SPFR), and stimulated whole saliva flow rate (SWSFR) were also made.
At 1 year after treatment, patients in IMRT arm had lower incidence of observer-rated severe xerostomia than patients in the 2DRT arm (39.3% v 82.1%; P = .001), parallel with a higher fractional SPFR (0.90 v 0.05; P < .0001), and higher fractional SWSFR (0.41 v 0.20; P = .001). As for patient's subjective feeling, although a trend of improvement in patient-reported outcome was observed after IMRT, recovery was incomplete and there was no significant difference in patient-reported outcome between the two arms.
IMRT is superior to 2DRT in preserving parotid function and results in less severe delayed xerostomia in the treatment of early-stage NPC. Incomplete improvement in patient's subjective xerostomia with parotid-sparing IMRT reflects the need to enhance protection of other salivary glands.
This study aims to evaluate the outcomes of adults hospitalized for tuberculosis in a higher-income region with low HIV prevalence.
A retrospective cohort study was conducted on all adults ...hospitalized for pulmonary and/or extrapulmonary tuberculosis in an acute-care hospital in Hong Kong during a two-year period. Microscopy and solid-medium culture were routinely performed. The diagnosis of tuberculosis was made by: (1) positive culture of M. tuberculosis, (2) positive M. tuberculosis PCR result, (3) histology findings of tuberculosis infection, and/or (4) typical clinico-radiological manifestations of tuberculosis which resolved after anti-TB treatment, in the absence of alternative diagnoses. Time to treatment ('early', started during initial admission; 'late', subsequent periods), reasons for delay, and short- and long-term survival were analyzed.
Altogether 349 patients were studied median(IQR) age 62(48-77) years; non-HIV immunocompromised conditions 36.7%; HIV/AIDS 2.0%. 57.9%, 16.3%, and 25.8% had pulmonary, extrapulmonary, and pulmonary-extrapulmonary tuberculosis respectively. 58.2% was smear-negative; 0.6% multidrug-resistant. 43.4% developed hypoxemia. Crude 90-day and 1-year all-cause mortality was 13.8% and 24.1% respectively. 57.6% and 35.8% received 'early' and 'late' treatment respectively, latter mostly culture-guided median(IQR) intervals, 5(3-9) vs. 43(25-61) days. Diagnosis was unknown before death in 6.6%. Smear-negativity, malignancy, chronic lung diseases, and prior exposure to fluoroquinolones (adjusted-OR 10.6, 95%CI 1.3-85.2) delayed diagnosis of tuberculosis. Failure to receive 'early' treatment independently predicted higher mortality (Cox-model, adjusted-HR 1.8, 95%CI 1.1-3.0).
Mortality of hospitalized tuberculosis patients is high. Newer approaches incorporating methods for rapid diagnosis and initiation of anti-tuberculous treatment are urgently required to improve outcomes.
This phase III randomized study compared concurrent cisplatin–radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 ...patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m2 weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval CI = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio HR = 0.71 95% CI = 0.5 to 1.0). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 95% CI = 0.59 to 1.4), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 95% CI = 0.3 to 0.88), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.
A wider application of living donor liver transplantation is limited by donor morbidity concerns. An observational cohort of 760 living donors accepted for surgery and enrolled in the Adult‐to‐Adult ...Living Donor Liver Transplantation cohort study provides a comprehensive assessment of incidence, severity and natural history of living liver donation (LLD) complications. Donor morbidity (assessed by 29 specific complications), predictors, time from donation to complications and time from complication onset to resolution were measured outcomes over a 12‐year period. Out of the 760 donor procedures, 20 were aborted and 740 were completed. Forty percent of donors had complications (557 complications among 296 donors), mostly Clavien grades 1 and 2. Most severe counted by complication category; grade 1 (minor, n = 232); grade 2 (possibly life‐threatening, n = 269); grade 3 (residual disability, n = 5) and grade 4 (leading to death, n = 3). Hernias (7%) and psychological complications (3%) occurred >1 year postdonation. Complications risk increased with transfusion requirement, intraoperative hypotension and predonation serum bilirubin, but did not decline with the increased center experience with LLD. The probability of complication resolution within 1 year was overall 95%, but only 75% for hernias and 42% for psychological complications. This report comprehensively quantifies LLD complication risk and should inform decision making by potential donors and their caregivers.
This large multicenter series from the A2ALL consortium provides a definitive report of the incidence and severity of live liver donor complications, and includes long‐term follow‐up allowing for a definition of the natural history of complications.
We aimed to evaluate the safety and efficacy of single-agent sunitinib in nasopharyngeal carcinoma (NPC).
Eligible patients had progressive disease after prior platinum-based chemotherapy. Sunitinib ...was given as continuous once-daily dosing of 37.5 mg in 4-week cycles until progression.
Thirteen patients were enrolled. Recruitment was stopped after two patients died of hemorrhagic events. All patients had previously received curative radiotherapy (RT) to nasopharynx/neck (including nine patients who had chemoradiotherapy). Patients received a median of three cycles of sunitinib. One patient was still on sunitinib with stable disease after 24 cycles. Hemorrhagic events occurred in nine patients (64%), including epistaxis in six, hemoptyses in three and hematemesis in two patients. Prior RT to thorax was significantly associated with hemoptyses (P = 0.03). Two patients with local tumor invasion into the carotid sheath developed fatal epistaxis/hematemesis within the first cycle of sunitinib, likely due to internal carotid blowout after tumor shrinkage.
Sunitinib demonstrated modest clinical activity in heavily pretreated NPC patients. However, the high incidence of hemorrhage from the upper aerodigestive tract in NPC patients who received prior high-dose RT to the region is of concern. Direct vascular invasion by tumors appeared to increase the risk of serious bleeding.
•An American Sign Language recognition model was developed using Leap Motion.•LSTM-RNN with kNN method was proposed for recognition 26 alphabets.•3D motion of hand gesture and relevant 30 features ...were extracted.•26 alphabets with recognition rate of 99.44% accuracy was obtained.
Though American sign language (ASL) has gained recognition from the American society, few ASL applications have been developed with educational purposes. Those designed with real-time sign recognition systems are also lacking. Leap motion controller facilitates the real-time and accurate recognition of ASL signs. It allows an opportunity for designing a learning application with a real-time sign recognition system that seeks to improve the effectiveness of ASL learning. The project proposes an ASL learning application prototype. The application would be a whack-a-mole game with a real-time sign recognition system embedded. Since both static and dynamic signs (J, Z) exist in ASL alphabets, Long-Short Term Memory Recurrent Neural Network with k-Nearest-Neighbour method is adopted as the classification method is based on handling of sequences of input. Characteristics such as sphere radius, angles between fingers and distance between finger positions are extracted as input for the classification model. The model is trained with 2600 samples, 100 samples taken for each alphabet. The experimental results revealed that the recognition rate for 26 ASL alphabets yields an average of 99.44% accuracy rate and 91.82% in 5-fold cross-validation with the use of leap motion controller.
The objectives of this study were to investigate the origin of highly discordant rifampin (rifampicin) (RMP) drug susceptibility test results obtained for Mycobacterium tuberculosis strains during ...proficiency testing. Nine Supra-National Tuberculosis Reference Laboratories tested the RMP susceptibilities of 19 selected M. tuberculosis strains, using standard culture-based methods. The strains were classified as definitely resistant (R) (n = 6) or susceptible (S) (n = 2) or probably resistant (PR) (n = 8) or susceptible (PS) (n = 3) based on rpoB mutations and treatment outcome. All methods yielded a susceptible result for the two S and three PS strains lacking an rpoB mutation and a resistant result for one R strain with a Ser531Leu mutation and one PR strain with a double mutation. Although the remaining 12 R and PR strains had rpoB mutations (four Asp516Tyr, three Leu511Pro, two Leu533Pro, one each His526Leu/Ser, and one Ile572Phe), they were all susceptible by the radiometric Bactec 460TB or Bactec 960 MGIT methods. In contrast, only one was susceptible by the proportion method on Löwenstein-Jensen medium and two on Middlebrook 7H10 agar. Low-level but probably clinically relevant RMP resistance linked to specific rpoB mutations is easily missed by standard growth-based methods, particularly the automated broth-based systems. Further studies are required to confirm these findings, to determine the frequency of these low-level-resistant isolates, and to identify technical improvements that may identify such strains.
Giardiasis: An Overview Leung, Alexander K C; Leung, Amy A M; Wong, Alex H C ...
Recent patents on inflammation & allergy drug discovery,
01/2019, Letnik:
13, Številka:
2
Journal Article
Recenzirano
Giardiasis is an important cause of waterborne and foodborne diarrhea, daycare center outbreaks, and traveler's diarrhea.
The study aimed to provide an update on the evaluation, diagnosis, and ...treatment of giardiasis.
A PubMed search was completed in Clinical Queries using the key terms "giardiasis", "Giardia lamblia", "Giardia duodenalis" and "Giardia intestinalis". The search strategy included metaanalyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to the English literature. Patents were searched using the key term "giardiasis" from www.freepatentsonline.com.
Giardiasis is caused by the protozoan parasite Giardia lamblia. The parasite is transmitted by the fecal-oral route, frequently through ingestion of contaminated water and food or person-to person transmission. Risk factors for infection include children in day-care settings, child-care workers, institutionalized individuals, travelers in endemic areas, ingestion of contaminated or recreational water, immunodeficiency, cystic fibrosis, and oral-anal sex. Approximately 50 to 75% of infected children are asymptomatic. Other children present acute or chronic diarrhea. Direct fluorescent antibody tests that detect intact organisms, enzyme immunoassays that detect soluble antigens, and multiplex real-time polymerase chain reaction assays that detect specific genes of the parasite in stool samples have improved sensitivity and specificity compared with microscopic examination of stool specimens for the detection of Giardia trophozoites or cysts. Drugs used in the treatment of symptomatic giardiasis are reviewed in this study. Moreover, recent patents related to the management of giardiasis are also discussed.
Metronidazole, tinidazole, and nitazoxanide are drugs of choice. Resistance to common antigiardial drugs has increased in recent years, therefore, the search for new molecular targets for antigiardial drugs is urgently needed. In general, treatment of asymptomatic carriers is not recommended. Purification of water supply is an important preventive measure.
Summary
Background
This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC).
Method
Oral MK-2206 at a dose of 200 mg was ...administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of
AKT
and
PIK3CA
mutation and
PIK3CA
amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate.
Results
21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9–7.3). The 6-month PFS rate was 43 % (95 % CI: 22–66 %) and the median OS was 10 months (95 % CI: 5.9 months–not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common (
n
= 6), followed by hyperglycemia (
n
= 2) and fatigue (
n
= 1). In the 12 tumor samples analyzed,
PIK3CA
amplification was detected in one patient’s primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease (
p
= 0.001).
Conclusion
The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.
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