An indirect treatment comparison of the efficacy of patisiran and tafamidis for the treatment of hereditary transthyretin-mediated amyloidosis with polyneuropathy

Background: Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a progressive, life-threatening disease. Until recently, tafamidis was the only approved pharmacotherapy. Patisiran significantly improved polyneuropathy and quality of life (QoL) in the phase III APOLLO trial. In the absence of direct comparisons, this analysis aimed to evaluate the comparative efficacy of tafamidis and patisiran in hATTR amyloidosis with polyneuropathy.

Research design and methods: Randomized controlled trial evidence for tafamidis was identified by systematic literature review. Indirect treatment comparisons were performed using the standard pairwise Bucher method for endpoints used in both APOLLO and the tafamidis Fx-005 trial: change from baseline in Neuropathy Impairment Score-lower limbs (NIS-LL), Norfolk QoL-Diabetic Neuropathy questionnaire (QoL-DN), NIS-LL response, and mBMI vs. placebo. Inter-trial population differences were assessed by sensitivity analysis.

Results: The base-case analysis (FAP Stage 1 APOLLO patients vs. intent-to-treat Fx-005 population) suggested patisiran had a greater treatment effect vs. tafamidis for all endpoints, with significant improvements in mean change in NIS-LL (–5.49) and QoL-DN (–13.10) from baseline to Month 18. Similar trends were observed in all sensitivity analyses.

Conclusions: In the absence of direct comparisons, this analysis suggests patisiran has a greater treatment effect than tafamidis in patients with hATTR amyloidosis with polyneuropathy.     

Present and future fertility preservation strategies for female cancer patients

As survival rates with cancer treatment are steadily increasing, many women are now facing sterility due to treatment induced ovarian failure. This review will attempt to summarize the options for trying to preserve fertility in these patients. The optimal approach depends on the type of cancer, the type of treatment (e.g., radiation and/or chemotherapy), time available till onset of treatment, patient's age, and whether the patient has a partner. Ovarian transposition remains the standard of care for women undergoing pelvic radiation, although it has been suggested that it may be combined with ovarian tissue cryopreservation. For patients about to receive chemotherapy or whole body radiation, in vitro fertilization (IVF) with embryo cryopreservation is a well established treatment with a good success rate. However, it requires delaying cancer treatment for 2 to 4 weeks and a partner or willingness to use donor sperm. When these criteria cannot be met, more experimental options include oocyte cryopreservation for later IVF and ovarian tissue cryopreservation. The tissue may be autotransplanted back to the pelvis, when the patient is in remission, to attempt spontaneous conception or subcutaneously for easy access of follicle aspiration for IVF. Alternatively, it may be xenografted to immunocompromised mice to induce follicle maturation in preparation for retrieval for IVF. Emerging treatment options for fertility preservation include medication to prevent chemotherapy-induced oocyte damage and oocyte construction from somatic cell nuclei. IVF with donor oocyte remains an established option with a very high success rate for those who fail to conceive with the above measures or who elect not to avail themselves to experimental procedures. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to demonstrate knowledge about fertility preservation when counseling appropriate female cancer patients, recall current clinical strategies to assist women cancer patients to try to maintain their fertility if they wish, and appraise future strategies as they develop.     

A case of colouterine fistula managed laparoscopically

Fistulas between the uterus and bowel are rarely reported. We report successful laparoscopic management of a colouterine fistula caused by a foreign body in the uterus. Fistulas between the gastrointestinal tract and the female genital tract are usually found between the vagina and rectum as a result of complications of childbirth or iatrogenic trauma. Communication between the uterus and bowel is rarely reported. We report successful laparoscopic management of an unusual case of colouterine fistula caused by a foreign body in the uterus.     

Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity

Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.     

Cell phones and male infertility: dissecting the relationship

There has been a tremendous increase in the use of mobile phones in the past decade and concerns are growing about the possible hazardous effects of radio-frequency electromagnetic waves (EMW) emitted by these devices on human health. Preliminary studies, though with limitations in study design, suggest a possible link between cell phone use and infertility. A recent study found that use of cell phones adversely affects the quality of semen by decreasing the sperm counts, motility, viability and morphology. Evidence of detrimental effect of mobile phones on male fertility is still equivocal as studies have revealed a wide spectrum of possible effects ranging from insignificant effects to variable degrees of testicular damage. Although previous studies suggested a role of cell phone use in male infertility, the mode of action of EMW emitted from cell phones on the male reproductive system is still unclear. EMW can affect the reproductive system via an EMW-specific effect, thermal molecular effect or combination of both. Studies performed on human males are scarce and therefore further studies with a careful design are needed to determine the effect of cell phone use on male-fertilizing potential.