Evidence summaries and recommendations from the international evidence‐based guideline for the assessment and management of polycystic ovary syndrome: Lifestyle management

Lifestyle is fundamental in chronic disease prevention and management, and it has been recommended as a first‐line treatment in the Australian polycystic ovary syndrome (PCOS) guideline 2011. The first international evidence‐based guideline on PCOS was developed in 2018, which expanded the scope and evidence in the Australian guideline. This paper summarizes the lifestyle recommendations and evidence summaries from the guideline. International multidisciplinary guideline development groups delivered the International Evidence‐based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018. The process followed the Appraisal of Guidelines for Research and Evaluation II and The Grading of Recommendations, Assessment, Development and Evaluation framework. Extensive communication and meetings addressed six prioritized clinical questions through five reviews. Evidence‐based recommendations were formulated before consensus voting within the panel. Evidence shows the benefits of multicomponent lifestyle intervention, efficacy of exercise and weight gain prevention with no specific diet recommended. Lifestyle management is the first‐line management in the intervention hierarchy in PCOS. Multicomponent lifestyle intervention including diet, exercise and behavioural strategies is central to PCOS management with a focus on weight and healthy lifestyle behaviours. The translation programme optimizes reach and dissemination for health professionals and consumers.     

Synthetic spatially graded Rac activation drives cell polarization and movement

Migrating cells possess intracellular gradients of active Rho GTPases, which serve as central hubs in transducing signals from extracellular receptors to cytoskeletal and adhesive machinery. However, it is unknown whether shallow exogenously induced intracellular gradients of Rho GTPases are sufficient to drive cell polarity and motility. Here, we use microfluidic control to generate gradients of a small molecule and thereby directly induce linear gradients of active, endogenous Rac without activation of chemotactic receptors. Gradients as low as 15% were sufficient not only to trigger cell migration up the chemical gradient but to induce both cell polarization and repolarization. Cellular response times were inversely proportional to the steepness of Rac inducer gradient in agreement with a mathematical model, suggesting a function for chemoattractant gradient amplification upstream of Rac. Increases in activated Rac levels beyond a well-defined threshold augmented polarization and decreased sensitivity to the imposed gradient. The threshold was governed by initial cell polarity and PI3K activity, supporting a role for both in defining responsiveness to Rac activation. Our results reveal that Rac can serve as a starting point in defining cell polarity. Furthermore, our methodology may serve as a template to investigate processes regulated by intracellular signaling gradients.     

Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells

Multiple myeloma (MM) is characterized by almost exclusive tropism of malignant cells for the bone marrow (BM) milieu. The survival and proliferation of malignant plasma cells have been shown to rely on interactions with nonmalignant stromal cells, in particular mesenchymal stromal cells (MSCs), in the BM microenvironment. However, the BM microenvironment is composed of a diverse array of cell types. This study examined the role of macrophages, an abundant component of BM stroma, as a potential niche component that supports malignant plasma cells. We investigated the proliferation of MM tumour cell lines when cultured alone or together with MSCs, macrophages, or a combination of MSCs and macrophages, using the carboxyfluorescein succinimidyl ester assay. Consistently, we observed increased proliferation of MM cell lines in the presence of either MSCs or macrophages compared to cell line-only control. Furthermore, the combined co-culture of MSCs plus macrophages induced the greatest degree of proliferation of myeloma cells. In addition to increased proliferation, MSCs and macrophages decreased the rate of apoptosis of myeloma cells. Our in vitro studies provide evidence that highlights the role of macrophages as a key component of the BM microenvironment facilitating the growth of malignant plasma cells in MM.     

Pre-operative Weight Loss Does Not Predict Weight Loss Following Laparoscopic Adjustable Gastric Banding

Background

This study aimed to test the hypothesis that the amount of weight lost on a mandatory 2-week pre-operative very-low-calorie diet (VLCD) would predict the longer-term outcomes of laparoscopic adjustable gastric banding (LAGB).

Methods

All patients treated with a primary LAGB from 21 October 2008 until 30 June 2010, who were prescribed a 2-week pre-operative VLCD, have been included in the study. Patient age, weight, BMI and excess weight (defined as weight above a BMI of 25) were extracted on the day of first visit, day of surgery and at the post-operative visits at 3, 12 and 24 months. From these data, percent excess weight loss (EWL) was calculated and compared at all time points.

Results

The weight loss achieved on a mandatory 2-week pre-operative diet did not predict weight outcomes at 2 years (r?=??0.008; p?=?0.931). Using multivariate analysis, the best predictor of 24-month percent EWL was percent EWL at 3 months post operation (sr²?=?0.34; p?=?0.003).

Conclusions

Results from a pre-operative diet should not be used to predict the ultimate outcome of bariatric surgery. The weight loss at 3 months following LAGB was a strong predictor of longer-term outcomes. There may be potential for improving longer-term results with LAGB by better supporting patients who are not achieving good weight loss at this early time point.     

Intensive Medical Weight Loss or Laparoscopic Adjustable Gastric Banding in the Treatment of Mild to Moderate Obesity: Long-Term Follow-up of a Prospective Randomised Trial

Background

Proven short-term effectiveness of obesity therapy should be re-evaluated in the long-term. The objective of this paper is to determine the long-term (10 years) outcome for patients from a randomised controlled trial (RCT).

Methods

A RCT in 2002 compared laparoscopic adjustable gastric band (LAGB) for obesity with non-surgical therapy. Follow-up has been conducted at 10 years. Eighty patients (BMI 30–35) were randomised to a non-surgical or a surgical program. Outcome data are available on 37 (92.5 %) of the surgical patients and 27 (62.5 %) of the non-surgical patients at 10 years.

Results

Weight change, the metabolic syndrome, quality of life, adverse events and direct costs of the surgical cohort were the main results of the study. A durable weight loss is present in the surgical group with a mean (SD) 10-year weight loss of 14.1 (7.7)?kg (63.4 % EWL), better than the non-surgical group (mean (SD)?=?0.4 (10.5)?kg; p?<?0.001). The metabolic syndrome was reduced from 14 to 4 of the 37 patients who completed 10 years within the LAGB groups. Proximal gastric enlargements occurred in 17 (30 %) of the 57 who had LAGB and removal of the band occurred in 7 (12 %). The annual maintenance costs including additional surgery was AUD $765 per patient per year.

Conclusions

Bariatric surgery with the LAGB can achieve long-term weight reduction which is better than a program of non-surgical therapy. There is also a sustained reduction of the metabolic syndrome. There is a significant maintenance requirement after LAGB.     

Preservation of sperm of cancer patients: extent of use and pregnancy outcome in a tertiary infertility center

Sperm cryopreservation is the best modality to ensure future fertility for males diagnosed with cancer. The extent to which cryopreserved sperm is actually used for impregnation, the fertility treatment options that are available and the success rates of these treatments have not been investigated in depth. The medical records of 682 patients who cryopreserved sperm cells due to cancer treatment were analyzed. Seventy of these patients withdrew their frozen sperm for fertility treatments over a 20-year period (most within the first 4 years after cryopreservation). Sperm quality of different malignancies and outcomes of assisted reproduction treatment (ART) for pregnancy achievement in relation to the type of treatment and the type of malignancy were evaluated. The results showed that the rate of using cryo-thawed sperm from cancer patients for fertility treatments in our unit was 10.3%. Sperm quality indices differed between different types of malignancies, with the poorest quality measured in testicular cancer. Conception was achieved in 46 of the 184 ART cycles (25%), and resulted in 36 deliveries. The use of intracytoplasmic sperm injection (ICSI) methodology yielded a significantly higher pregnancy rate (37.4%) than intrauterine insemination (IUI; 11.5%) and was similar to other groups of infertile couples using these modalities. In vitro fertilization (IVF) failed to produce pregnancies. In conclusion, the rate of use of cryopresseved sperm in cancer patients is relatively low (10.3%). Achievement of pregnancies by ICSI presents the best option but when there are enough stored sperm samples and adequate quality, IUI can be employed. Cryopreservation is nevertheless the best option to preserve future fertility potential and hope for cancer patients.     

Intratumoral inflammation is associated with more aggressive prostate cancer

Purpose

Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease.

Methods

The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively.

Results

No inflammation was found in 49 men (17 %), while 153 (53 %) and 85 (30 %) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44 %) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95 % CI 1.02–4.24), but not after adjusting for pathologic features.

Conclusions

Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease.