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.     

Pain management in ambulatory surgery.

Successful ambulatory surgery is dependent on analgesia that is effective, has minimal adverse effects, and can be safely managed by the patient at home after discharge. A number of studies have identified that the provision of effective postoperative analgesia is inadequate for a significant proportion of patients. The following discussion details the current available analgesic options for ambulatory surgery patients and the rationale for their use. Preemptive analgesia should be given to all patients unless there are specific contraindications. Consideration should be given to the use of long-acting oral COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) and long-acting oral opioids to treat postoperative pain. A standardized multimodal postdischarge analgesic regimen tailored to the patient's expected postoperative pain levels should be prescribed. Patient follow-up by telephone questionnaire will confirm those surgical procedures that result in mild or moderate-to-severe postoperative pain and the effectiveness of treatment plans.     

Pulmonary artery balloon counterpulsation for right ventricular failure after right ventriculotomy in the swine

To assess the efficacy of intrapulmonary balloon counterpulsation in the management of right ventricular failure after right ventriculotomy, we undertook an experimental study in a swine model. To mimic the clinical settings more closely, (1) we left the automatic control of the heart intact (2) did not use cardiopulmonary bypass to support the left side of the heart, and (3) induced right ventricular failure by means of a generous surgical incision (50% to 70% of the anterior wall) of the right ventricle. The criteria set for right ventricular failure were (1) 50% increase in right ventricular end-diastolic pressure, (2) 30% decrease in mean arterial pressure, and (3) 30% decrease in cardiac output. Right ventricular failure was attained in all animals studied: A 230% increase in right ventricular end-diastolic pressure, a 43% decrease in cardiac output, and a 34% decrease in mean arterial pressure were evident after the right ventriculotomy. A specially designed intrapulmonary balloon catheter (Datascope Corp., Oakland, N.J.) was placed into the left pulmonary artery through the right ventricular outflow tract. A Datascope console was used for counterpulsation. Effects of counterpulsation for 40 minutes in a 1:1 mode were assessed after surgical induction of right ventricular failure in 14 swine. Each animal served as its own control. The mean hemodynamic changes are outlined: Right ventricular end-diastolic pressure decreased by 48.9% (p = 0.01). Mean arterial pressure increased by 68.8% (p = 0.01) and cardiac output by 44.2% (p = 0.01). Histologic studies disclosed no morphologic damage to the pulmonary artery or valve in the specimens analyzed. In addition, these results were compared with those in a second group of seven swine in which right ventricular failure was induced by right ventriculotomy and a balloon was placed into the left pulmonary artery but not activated. These results of short-term counterpulsation should be evaluated in a longer term model so as to mimic more closely the clinical setting. If the hemodynamic benefits are duplicated, intrapulmonary balloon counterpulsation should be considered as a simple, effective device when right ventricular failure develops after right ventriculotomy. It effectively improves right ventricular function without damaging the pulmonary artery or valve.     

Peptide growth factors and wound healing

An analysis of peptide growth factors and wound healing should not fail to give credit to its foundations in cancer research. Add the recent advances in peptide chemistry and molecular genetics that have permitted complete definitions and in vivo studies for the first time. The result is an enormous break-through in wound healing research. The potential for understanding and then using the growth factors to enhance healing in the aged or debilitated is incalculable.     

Swaziland: Perspectives in School Health

Following major quantitative expansions of the educational system in Swaziland during the two decades since independence, the focus has shifted to improving efficiency. Efficiency of any educational system depends mainly on the characteristics of children entering school. Although Swaziland is not among the poorest countries, infant child mortality rates still reflect less than optimum living conditions and parental knowledge of child nutrition and disease prevention and management. Although access to primary schooling is universal, there is substantial waste during the early years of school through dropout and repetition, both associated with low socioeconomic status. School performance can be increased at little extra cost through increasing the nutrition and health status of students before school entry and through the early school years. In Swaziland, many activities are carried out to provide physical and mental health care to students. Coordinating these efforts and formulating clear policy on school health through cooperation among key ministries and nongovernmental organizations remains to be done.     

VASOCONSTRICTION IN THE RENAL VASCULAR BED DURING EXERCISE: STUDIES IN CONTROL AND HEART FAILURE RABBITS

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.     

Effects of antidepressant medication on sexual function: a controlled study

There has been little systematic study of the types of sexual dysfunction produced by antidepressant medication or of the frequency with which this type of adverse effect occurs. The authors report results of a double-blind study in which the effects of imipramine, phenelzine, and placebo on specific aspects of sexual function were assessed in depressed outpatients before and after 6 weeks of treatment. Both active treatments were associated with a high incidence of adverse changes in sexual function and produced significantly more adverse effects on sexual function than placebo. Orgasm and ejaculation were impaired to a greater extent than erection. Adverse sexual function changes secondary to antidepressant medication occurred frequently in both men and women, although men reported a higher incidence. Antidepressant-related sexual dysfunction may be of clinical importance for medication compliance in view of current recommendations that antidepressants be administered for longer periods as maintenance therapy or for prophylaxis.