Ovarian damage from chemotherapy and current approaches to its protection.

BACKGROUND: Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to the effects of chemotherapy and radiotherapy. While oocyte, embryo and ovarian cortex cryopreservation can help some women with cancer-induced infertility achieve pregnancy, the development of effective methods to protect ovarian function during chemotherapy would be a significant advantage. OBJECTIVE AND RATIONALE: This paper critically discusses the different damaging effects of the most common chemotherapeutic compounds on the ovary, in particular, the ovarian follicles and the molecular pathways that lead to that damage. The mechanisms through which fertility-protective agents might prevent chemotherapy drug-induced follicle loss are then reviewed. SEARCH METHODS: Articles published in English were searched on PubMed up to March 2019 using the following terms: ovary, fertility preservation, chemotherapy, follicle death, adjuvant therapy, cyclophosphamide, cisplatin, doxorubicin. Inclusion and exclusion criteria were applied to the analysis of the protective agents. OUTCOMES: Recent studies reveal how chemotherapeutic drugs can affect the different cellular components of the ovary, causing rapid depletion of the ovarian follicular reserve. The three most commonly used drugs, cyclophosphamide, cisplatin and doxorubicin, cause premature ovarian insufficiency by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. They also cause an increase in damage to blood vessels and the stromal compartment and increment inflammation. In the past 20 years, many compounds have been investigated as potential protective agents to counteract these adverse effects. The interactions of recently described fertility-protective agents with these damage pathways are discussed. WIDER IMPLICATIONS: Understanding the mechanisms underlying the action of chemotherapy compounds on the various components of the ovary is essential for the development of efficient and targeted pharmacological therapies that could protect and prolong female fertility. While there are increasing preclinical investigations of potential fertility preserving adjuvants, there remains a lack of approaches that are being developed and tested clinically.

Increased long-term mortality in patients less than 55 years old who have undergone knee replacement for osteoarthritis: results from the Swedish Knee Arthroplasty Register.

Patients with osteoarthritis undergoing knee replacement have been reported to have an overall reduced mortality compared with that of the general population. This has been attributed to the selection of healthier patients for surgery. However, previous studies have had a maximum follow-up time of ten years. We have used information from the Swedish Knee Arthroplasty Register to study the mortality of a large national series of patients with total knee replacement for up to 28 years after surgery and compared their mortality with that of the normal population. In addition, for a subgroup of patients operated on between 1980 and 2002 we analysed their registered causes of death to determine if they differed from those expected. We found a reduced overall mortality during the first 12 post-operative years after which it increased and became significantly higher than that of the general population. Age-specific analysis indicated an inverse correlation between age and mortality, where the younger the patients were, the higher their mortality. The shift at 12 years was caused by a relative over-representation of younger patients with a longer follow-up. Analysis of specific causes of death showed a higher mortality for cardiovascular, gastrointestinal and urogenital diseases. The observation that early onset of osteoarthritis of the knee which has been treated by total knee replacement is linked to an increased mortality should be a reason for increased general awareness of health problems in these patients.

Migration of the acetabular component after revision with impacted morselized allografts: a radiostereometric 2-year follow-up analysis of 21 cases.

In a consecutive series of hip revisions due to mechanical loosening, using impacted morselized allografts and cement, we followed 21 acetabular components by radiostereometric analysis (RSA) during 2 years. All but 1 acetabular component migrated in the proximal direction (median 2.1 (0.5-6.4) mm). 6 components migrated in the medial direction (median 0.8 (0.4-1.2) mm) and 6 in the lateral (median 0.8 (0.4-2.0) mm). 14 components migrated in the posterior direction (median 0.8 (0.3-2.3) mm) and 1 in the anterior 0.6 mm. The migration rate gradually decreased in all directions, but 7 acetabular components still migrated in at least 1 direction (median 0.3-0.6 mm) between 1.5 and 2 years postoperatively.

Epidemiology of childhood injuries in Reykjavík 1974-1991.

OBJECTIVE: To determine and analyse the incidence of childhood injuries in Reykjavík 1974-1991. DESIGN: Descriptive, retrospective study. SETTING: Reykjavík City district with a mean number of 88700 inhabitants, of which 23.4% were children under 15 years of age. SUBJECTS: All children 0-14 years old who came to the emergency department at Reykjavík City Hospital because of an injury. MAIN OUTCOME MEASURES: Number of injured children per 1000 children per year. RESULTS: 111726 cases were studied. The total incidence of injuries increased from 275 per 1000 children per year in 1974-76 to 327 in 1980-82, but it then decreased to 275 in 1989-91. The injury incidence for 0-4 years old decreased from 353 in 1980-82 to 259 in 1989-91. The injury incidence for children 5-9 years old was 249 in 1989-91. The injury incidence for children 10-14 years old increased from 235 in 1974-76 to 336 in 1980-82, and in 1989-91 it was 321. The incidence of hospital admissions was 7.6 per 1000 children per year, or 2.6%. The child accident mortality rate in Reykjavík from 1987-1991 was 6.5 per 100000 children per year. CONCLUSION: Childhood injuries in Reykjavík are far too many, and a major effort is needed to reduce their number.