Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.     

A phase II study of ifosfamide in endometrial cancer

Around 32% of all patients with endometrial carcinoma relapse after primary therapy. The outlook for these patients is poor. Ifosfamide (IFX) has activity in a number of gynaecological malignancies and was selected for evaluation in this disease. The aims of this study were to assess the activity and toxicity of IFX in recurrent endometrial carcinoma no longer amenable to radical local treatment. In all, 16 evaluable patients with symptomatic advanced metastatic or recurrent disease entered a phase II study of this drug. Patients received IFX (5 g/m²) as a 24-h infusion, with mesna (8 g/m²) given during and for 12 h following IFX to prevent urothelial toxicity. Treatment was repeated every 21 days. Two patients showed evidence of response [one complete response (CR) of 3 months and one partial response (PR) lasting 5 months]. Most patients experienced nausea and vomiting, and WHO grade 3/4 alopecia invariably occurred after two or more cycles. Four patients developed severe (grade 3/4) IFX/mesna CNS toxicity, and four other patients had mild (grade 1/2) CNS toxicity. Significant myelosuppression was seen in 3/41 cycles. Haematuria was uncommon and invariably mild. There were two toxic deaths (one due to grade 4 CNS toxicity and one due to septicaemia). IFX has activity in endometrial carcinoma, but responses are of limited duration and toxicity is considerable.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Social aspects of AIDS-related stigma in rural Uganda

In the process of collecting sexual behaviour data through in-depth interviews, 24 respondents offered information on stigma related to HIV-1 infection. Observations of social relations in public places and families of infected individuals were made. The findings suggest that although HIV/AIDS-related stigma has had adverse effects on treatment seeking behaviour of PWAs and coping mechanisms of their families, a more tolerant attitude is starting to emerge in this area. Probably, due to improvements in counselling services and home care schemes for those with AIDS. This supports the call for increased investments in counselling and community development aimed at caring for people with AIDS (PWAs).     

Systemic steroid prophylaxis for cataract surgery in patients with posterior uveitis

Cataract remains difficult to manage in patients with uveitis affecting the posterior segment of the eye due to the high risk of postoperative complications, especially cystoid macular oedema, even in eyes in which inflammation has been completely suppressed preoperatively. A standard regimen of preoperative and perioperative systemic steroid prophylaxis was introduced into the uveitis clinic in order to prevent uveitis-related cystoid macular oedema in the postoperative period. The aim of this study was to assess if this policy resulted in an improvement in the visual recovery. Data from a single consecutive clinical series of 30 extracapsular cataract extraction procedures performed in 24 patients with posterior uveitis were collected retrospectively. Nineteen procedures were performed before and 11 after the introduction of the regimen of steroid prophylaxis. Success was graded according to the Snellen acuity at six months, the number of lines improvement in visual acuity by six months and the time from the operation date for acuity to recover to its best postoperative level. The median visual acuity after six months was 20/30 in the prophylaxis group compared with 20/80 in the controls (p = 0.052), representing a median improvement of five lines in the prophylaxis group and three lines in the controls (not significant). The eyes receiving prophylaxis achieved their best acuity in 1.8 months (median) compared with 5.9 months for the control group (p<0.01). This was not attributable to the longer period of follow-up in the control group and was independent of IOL implantation or the influence of any individual postoperative complication. When pseudophakic eyes were considered in isolation, the median acuity at six months was also better in the prophylaxis group (p = 0.023). The results suggest that preoperative systemic steroid prophylaxis may benefit the patient by hastening postoperative visual recovery independently of IOL implantation.     

Simultaneous irradiation and imaging of blood vessels during pulsed laser delivery

BACKGROUND AND OBJECTIVE: Simultaneous irradiation and viewing of 10-120 microm cutaneous blood vessels were performed to investigate the effects of 2-micros 577-nm dye laser pulses. STUDY DESIGN/MATERIALS AND METHODS: A modified scanning laser confocal microscope recorded vessel response to different radiant exposures (J/cm2). Probit analysis determined the 50% probability ("threshold") radiant exposure necessary to cause embolized or partly occluding coagula, coagula causing complete blood flow stoppage, and hemorrhage. RESULTS: A statistically significant difference in the threshold radiant exposure existed for each damage category for blood vessels 10-30 microm in diameter, but not for larger vessels. For vessels over 60 microm, complete flow stoppage was unattainable; increasing laser pulse energy produced hemorrhage. In larger vessels, coagula often were attached to the superficial vessel wall while blood flowed underneath. Monte Carlo optical and finite difference thermal modeling confirmed experimental results. CONCLUSION: These results provide insight into the role of pulse duration and vessel diameter in the outcome of pulsed dye laser irradiation.     

Information needs in terminal illness.

Despite evidence that doctor-patient communication affects important patient outcomes, patient expectations are often not met. Communication is especially important in terminal illness, when the appropriate course of action may depend more on patient values than on medical dogma. We sought to describe the issues important to terminally ill patients receiving palliative care and to determine whether patient characteristics influence the needs of these patients. We utilized a multimethod approach, first conducting interviews with 22 terminally ill individuals, then using these data to develop a more structured instrument which was administered to a second population of 56 terminally ill patients. Patient needs and concerns were described and associations between patient characteristics and issues of importance were evaluated. Seven key issues were identified in the initial interviews: change in functional status or activity level; role change; symptoms, especially pain; stress of the illness on family members; loss of control; financial burden and conflict between wanting to know what is going on and fearing bad news. Overall, respondent needs were both disease- and illness-oriented. Few easily identifiable patient characteristics were associated with expressed concerns or needs, suggesting that physicians need to individually assess patient needs. Terminally ill patients receiving palliative care had needs that were broad in scope. Given that few patient characteristics predicted responses, and that the majority opinion may not accurately reflect that of an individual patient, health care providers must be aware of the diverse concerns among this population and individualize assessment of each patient's needs and expectations.     

Searching for solutions: health concerns expressed in letters to an east African newspaper column

This study examined health care questions from an unusual data set: 1252 unsolicited letters written over a three-year period to an advice column in an East African newspaper. Analysis of the letters was a non-intrusive method of ascertaining prevalent health questions and opinions. People wrote seeking information, advice, solutions, and reassurance about health problems. Emotions expressed in the letters ranged from hope to fear and frustration. The written format allowed questions which are generally too embarrassing or stigmatized to present in other public or interpersonal settings. More than half the total letters raised questions about sexual behaviour, sexually transmitted diseases, and HIV/AIDS. The letters present not only personal health concerns, but also expectations of health-care quality and reflections on the medical options presently available in Uganda. As a whole, the letters express dissatisfaction not only with the outcomes of health encounters, but with the process. Of the letter writers with specific physical complaints, more than one-third had already sought medical care and were dissatisfied with the results. The letters were seeking solutions, especially for alleviation of symptoms and discomfort. Almost equally prevalent was a plea for accurate and relevant health information; people not only want to feel better, but they also want to understand their own health.     

Simple technique for anvil insertion in stapled circular colorectal anastomoses

The benefits of circular stapling devices are obvious. The introduction of staplers with detachable anvils has simplified the stapling procedure even more than the original instruments. A simple technique for placing the anvil and pursestring are described.     

Induction of immunogenicity of monoclonal antibodies by conjugation with drugs

Human anti-mouse antibody has been a nearly consistent result of human clinical trials utilizing murine antibodies. It is generally anticipated that the problem of human anti-mouse antibody will be reduced as genetically engineered, more human ("humanized") antibodies become available. It is not clear, however, what effect chemical modification of such "humanized" antibodies will have on their immunogenicity. The present studies utilize a mouse antibody and rat host model to explore aspects of this question. Rats injected with unmodified mouse monoclonal antibodies failed to mount anti-mouse immune responses, presumably due to their phylogenetic relatedness. In contrast, rats injected with a Vinca immunoconjugate mounted strong anticonjugate antibody responses that were directed primarily against the linker portion of the conjugate. The in vivo serum pharmacokinetics of 125I-labeled antibody and conjugates were evaluated in rats with existing anticonjugate antibody. The peak serum level attained was inversely correlated with the level of reactivity of the anticonjugate antibody with the injected compound. This model provides a potentially useful tool for exploration of the immunogenicity of drug, toxin, or radionuclide monoclonal antibody conjugates.