Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

Peripheral Vascular Complication from Coronary Angiography: a Case Report of Cholesterol Embolization

A 65-year-old man developed acute limb ischemia, severe abdominal wall and lower limb livedo reticularis following a coronary angiogram. The differential diagnoses of acute limb ischemia and multiple cholesterol emboli syndrome (MCES) are discussed. This work was performed at Long Island Jewish Medical Center, 270-05, 76^th Avenue, New Hyde Park, NY 11040.     

Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial

The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers.     

Endonasal carbon-dioxide laser assisted dacryocystorhinostomy verses external dacryocystorhinostomy

This is a prospective, non-randomized study to evaluate and compare the results, morbidity and surgical time for endonasal carbon-dioxide laser assisted dacryocystorhinostomy and external dacryocystorhinostomy. 70 consecutive patients of chronic dacryocystitis with nasolacrimal duct obstruction were selected for the study. 36 patients under went endonasal CO2 laser assisted dacryocystorhinostomy and 34 had external dacryocystorhinostomy. Selection of the type of operation was left to the patient's choice. All the patients had preoperative counseling and both the procedures were explained in detail with their advantages and disadvantages. Patients not willing for the external incision were selected for endonasal laser assisted dacryocystorhinostomy and others were operated via external approach. Silicone tubes were put in all the patients for three months after surgery. The final follow up was 12 months after the removal of silicone tubes. The patency of the lacrimal passage was confirmed by irrigation, and patients were questioned about their symptoms. The success rates, 12 months after removal of silicone tubes were 100% in endonasal CO2 laser assisted dacryocystorhinostomy and 88.24% in external dacryocystorhinostomy. The surgical time of endonasal laser assisted dacryocystorhinostomy was 38 minutes as compared to 62 in external dacryocystorhinostomy. Complication rate in both groups was almost equal. Thus, we came to the conclusion that Endonasal CO2 laser assisted dacryocystorhinostomy is a better surgical option to external dacryocystorhinostomy in cases of chronic dacryocystitis with nasolacrimal duct obstruction, with shorter surgical time.     

Measuring the efficacy of antiepileptic drugs.

Clinical trials of new antiepileptic drugs (AEDs) include regulatory studies aimed at demonstrating efficacy and reasonable safety, post-marketing open-open label studies and longer term outcome studies. Regulatory trials involve a carefully selected population of patients and are conducted under rigorously standardised conditions. Data from such studies cannot often be translated into clinical practice. Pragmatic post-marketing studies using flexible dosing schedules allow clinicians to better judge the utility of the new drug in a wider population of patients with epilepsy and decide the most appropriate dosing schedules. This paper discusses some of the issues surrounding the measurement of efficacy of new AEDs in both pre- and post-marketing phases of their development. All of the newer AEDs are initially used in patients with refractory partial seizures as adjunctive treatment. These trials are generally parallel-group studies although cross-over designs have been employed. The use of placebo-control is uncontroversial in this type of study. Efficacy endpoints are generally manipulations of seizure frequency on study drug compared to control. Global outcome measures and health related quality of life scores can also be used to measure efficacy. As the standard AEDs are associated with a high rate of seizure remission in patients who receive them as monotherapy, demonstration of superior efficacy of a new agent in a comparative trial will require large numbers of patients in a design that takes into account the natural history of treated epilepsy. Comparing investigational agents to a standard AED in an 'active-control' study with demonstration of equivalent efficacy would seem to be an acceptable way of assessing efficacy of new AEDs in this population. Some regulators, however, do not accept equivalence as proof of efficacy and insist on demonstration of superiority compared to a control. The use of placebo alone in the control group is ethically dubious. Several innovative study designs have, therefore, been used to satisfy regulatory requirements, while maintaining patient safety including withdrawal to monotherapy using high versus low dose comparators. Observational outcome studies provide the best opportunity of exploring the long-term utility of individual AEDs. Such studies largely follow standard clinical practice and need considerable time and resources. They can, however, yield valuable information about the effectiveness of AEDs in everyday clinical practice. Data from regulatory trials should be complemented by postmarketing studies and longer term studies of outcome to help clinicians decide the best way of utilising new AEDs and establishing their role in the therapeutic armamentarium.     

Hazards of smoking

A strong association exists between cigarette smoking and several diseases namely, cancer of the lung, bronchitis and emphysema, cancer of the larynx, oral cavity and oesophagus, gastric and duodenal ulcers, Crohn's disease, cancer of the bladder, coronary artery disease, macrocytosis, polycythaemia, leukaemia, etc. This is due to the harmful constituents of cigarette and other modalities smoking. Smokers not only harm themselves but also harm those around. Foetal malformations, abortions, stillbirths, prematurity and low birth weight are common in smoker mothers. These are the effects of passive smoking. There is no safer cigarette in the market even by lowering its harmful constituents. Mass education about the hazards of smoking with emphasis on complete stoppage of smoking is the only way to prevent its rising incidence.