The impact of in-house pathology services on downstaging cervical cancer in Tanzania over an 18-year period.

PURPOSE: Reducing time between cancer screening, diagnosis, and initiation of treatment is best achieved when services are available in the same hospital. Yet, comprehensive cancer centers are typically unavailable in low- and middle-income countries (LMICs), where resources are limited and services scattered. This study explored the impact of establishing an in-house pathology laboratory at the largest public cancer hospital in Tanzania on the downstaging of cervical cancer. METHODS: We examined clinical datasets of 8,322 cervical cancer patients treated at the Ocean Road Cancer Institute (ORCI). The first period included patients treated from 2002 to 2016, before establishment of the pathology laboratory at ORCI; the second period (post-pathology establishment) included data from 2017 to 2020. Logistic regression analysis evaluated the impact of the pathology laboratory on stage of cervical cancer diagnosis. RESULTS: Patients treated during the post-pathology period were more likely to be clinically diagnosed at earlier disease stages compared to patients in the pre-pathology period (pre-pathology population diagnosed at early disease stage: 44.08%; post-pathology population diagnosed at early disease stage: 59.38%, p < 0.001). After adjustment for age, region of residence, and place of biopsy, regression results showed patients diagnosed during the post-pathology period had higher odds of early stage cervical cancer diagnosis than patients in the pre-pathology period (OR 1.35, 95% CI (1.16, 1.57), p < 0.001). CONCLUSIONS: Integrated and comprehensive cancer centers can overcome challenges in delivering expedited cervical cancer diagnosis and treatment. In-house pathology laboratories play an important role in facilitating timely diagnosis and rapid treatment of cervical and possibly other cancers in LMICs.

The Effects of Creatine Monohydrate Loading on Exercise Recovery in Active Women throughout the Menstrual Cycle.

Creatine supplementation improves anaerobic performance and recovery; however, to date, these outcomes have not been well explored in females. This study evaluated the effect of creatine monohydrate loading on exercise recovery, measured by heart rate variability (HRV) and repeated sprint performance, in women across the menstrual cycle. In this randomized, double-blind, cross-over study, 39 women (mean ± standard deviation: age: 24.6 ± 5.9 years, height: 172.5 ± 42.3 cm, weight: 65.1 ± 8.1 kg, BF: 27.4 ± 5.8%) were randomized to a creatine monohydrate (n = 19; 20 g per day in 4 × 5 g doses) or non-caloric PL group (n = 20). HRV was measured at rest and after participants completed a repeated sprint cycling test (10 × 6 s maximal sprints). Measurements were conducted before and after supplementation in the follicular/low hormone and luteal/high hormone phases. Creatine monohydrate supplementation did not influence HRV values, as no significant differences were seen in HRV values at rest or postexercise. For repeated sprint outcomes, there was a significant phase × supplement interaction (p = 0.048) for fatigue index, with the greatest improvement seen in high hormone in the creatine monohydrate group (-5.8 ± 19.0%) compared to changes in the PL group (0.1 ± 8.1%). Sprint performance and recovery were reduced by the high hormone for both groups. Though not statistically significant, the data suggests that creatine monohydrate could help counteract performance decrements caused by the high hormone. This data can help inform creatine monohydrate loading strategies for females, demonstrating potential benefits in the high hormone phase.

Association of MTHFR Polymorphisms With Leukoencephalopathy Risk in Patients With Primary CNS Lymphoma Treated With Methotrexate-Based Regimens.

OBJECTIVES: The folate antagonist high-dose methotrexate (HD-MTX) is integral to induction chemotherapy for primary CNS lymphoma (PCNSL); however, it can be associated with leukoencephalopathy. Methylenetetrahydrofolate reductase (MTHFR) is involved in intracellular folate depletion. We assessed whether MTHFR polymorphisms affect the risk of leukoencephalopathy. METHODS: We retrospectively searched our database at the Massachusetts General Hospital for newly diagnosed PCNSL treated with HD-MTX (without radiotherapy nor intrathecal chemotherapy). RESULTS: Among 68 patients with PCNSL, MTHFR polymorphisms were found in 60 individuals (88.2%) including a 677C→T genotype, a 1298A→C genotype, or a combined 677C→T/1298A→C genotype. Neither MTX clearance nor response to induction therapy was affected by specific genotypes, and complete response was achieved in 72.1% of patients by HD-MTX-based induction. However, the 1298A→C genotype was associated with increased frequency and severity of leukoencephalopathy over time (odds ratio 4.0, CI 1.5-11.4). Such genotype predicted treatment-induced leukoencephalopathy with a sensitivity of 71.0% and a specificity of 62.2% (area under the curve 0.67, CI 0.5-0.8; p = 0.019). While progression-free survival did not differ in genotype-based subgroups, overall survival was lower for the 1298A→C genotype. DISCUSSION: The MTHFR 1298A→C genotype may serve to identify patients with PCNSL at elevated risk of HD-MTX-induced leukoencephalopathy. This seems to translate into reduced survival, potentially due to decreased functional status.

A Randomized Controlled Trial of Changes in Fluid Distribution across Menstrual Phases with Creatine Supplementation.

This study examined the effects of creatine (Cr) loading on body mass (BM) and fluid markers of total body water (TBW), extra-cellular fluid (ECF), and intra-cellular fluid (ICF) across the menstrual cycle (MC). Thirty moderately active females, either naturally-menstruating (NM) or using hormonal contraceptives (HC), were randomized to Cr (Cr; 4 × 5 g/day of creatine monohydrate for 5 days; n = 15) or a non-caloric placebo (PL; n = 15) using a double-blind, placebo-controlled design, with a menstrual phase crossover. BM, TBW, ECF, and ICF were measured at pre- and post-supplementation in randomized order of follicular phase (FP; NM: MC days 0−8, HC: inactive pill days) or luteal phase (LP; NM: ≤15 days from next projected cycle start date, HC: active pill days) using bioelectrical impedance spectroscopy. Acute hydration status and salivary estrogen were used as covariates. Change in BM was not different between groups across MC ([PL-Cr] Δ 0.40 ± 0.50 kg; p = 0.427) or between MC phase across groups ([FP-LP] Δ 0.31 ± 0.48 kg; p = 0.528). TBW (p = 0.802), ECF (p = 0.373), and ICF (p = 0.795) were not different between supplement groups at pre-supplementation/FP time points. There were no significant differences between the NM and HC subjects at any time point, for any outcome (p > 0.05). Following LP supplementation, significant changes were observed in TBW (Cr: Δ 0.83 ± 0.38 L, PL: Δ −0.62 ± 0.38 L; p = 0.021), ECF (Cr: Δ 0.46 ± 0.15 L, PL: Δ −0.19 ± 0.15 L; p = 0.013), and ICF (Cr: Δ 0.74 ± 0.23 L, PL: Δ −0.02 ± 0.23 L; p = 0.041). These data demonstrate an increase in all fluid compartments in the LP following Cr loading, without observed alterations in body weight for females.

Evaluation of pre-workout and recovery formulations on body composition and performance after a 6-week high-intensity training program.

Introduction: Activities such as high-intensity resistance training (HIRT) and high-intensity interval training (HIIT) may be more time-efficient modes to stimulate rapid changes in performance and body composition. There is little research evaluating the combined effects of HIRT and HIIT on body composition and strength, particularly when paired with nutritional supplementation. Purpose: To evaluate the chronic effects of pre- and post-workout supplementation on body composition and strength, and to understand sex-specific responses. Materials and methods: 64 untrained males (n = 23) and females (n = 41) (mean ± standard deviation; age: 33.2 ± 10.0 years; %fat: 31.6 ± 7.4%) were randomized to either (1) pre-post supplementation [SUP (n = 25); pre = multi-ingredient caffeine/HMB/vit D; post = whey protein/carbohydrates/glucosamine/vitamins], (2) placebo [PL (n = 24); non-caloric], or (3) control [CON (n = 15)]. All participants completed one repetition max (1RM) strength testing for leg press and bench press at baseline and week 6. Estimates of fat mass (FM) and lean mass (LM) were measured via dual energy x-ray absorptiometry. Participants in the SUP or PL group completed a 6-week supervised exercise intervention consisting of a full-body HIRT workout (3 × 6-8 reps) followed by a HIIT treadmill run (6 × 1 min run: 1 min rest) twice per week. Outcomes were evaluated by separate repeated measure ANOVAs (2 × 3). Results: There were no differences in FM between groups or sex (p = 0.133-0.851). LM increased from baseline to post-testing for all groups [Mean difference [MD(Post-Pre) ± Standard Error (SE) = 0.78 ± 0.12 kg; p < 0.001]. While not significant (p = 0.081), SUP gained more LM compared to PL [MD(SUP-PL) ± SE = 3.5 ± 3.3 kg] and CON [MD(SUP-CON) ± SE = 5.2 ± 3.8 kg]. LM increased over time for both males (0.84 ± 0.24 kg; p = 0.003) and females (0.73 ± 0.14 kg; p < 0.001). The SUP group resulted in a significant increase in 1RM leg press compared to the CON group (89.9 ± 30.8 kg; p = 0.015), with no significant differences compared to PL (p = 0.409). The SUP group had greater increases in 1RM bench press compared to the CON group (9.8 ± 1.8 kg; p < 0.001), with no significant differences compared to PL (p = 0.99). Both sexes increased upper- (5.5 ± 0.7 kg; p < 0.001) and lower-body strength (69.8 ± 4.5 kg p < 0.001) with training. Conclusion: Nutrient supplementation timing appears to augment body composition changes and strength compared to control. Pre-/post-nutrient timing may support greater increases in LM and lower- and upper-body strength in both men and women. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04230824?cond=NCT04230824&draw=2&rank=1], identifier [NCT04230824].