Association between Hispanic Ethnicity and Greater Expectation of Benefit from Acupuncture or Massage for Pain in Cancer.

Individuals living with cancer and survivors of cancer who self-identify as Hispanic experience higher pain burden and greater barriers to pain management compared with their non-Hispanic counterparts. The Society for Integrative Oncology-ASCO guideline recommends acupuncture and massage for cancer pain management. However, Hispanic individuals' expectations about these modalities remain under-studied and highlight a potential barrier to treatment utilization in this population. We conducted a subgroup analysis of baseline data from two randomized clinical trials to evaluate ethnic differences in treatment expectations about integrative pain treatment modalities among Hispanic and non-Hispanic cancer patients and survivors of cancer. The Mao Expectancy of Treatment Effects (METE) instrument was used to measure treatment expectancy for electro-acupuncture, auricular acupuncture, and massage therapy. Results of this study demonstrated that Hispanic participants reported greater expectation of benefit from electroacupuncture, auricular acupuncture, and massage (all P < 0.01). After controlling for age, gender, race, and education, Hispanic ethnicity remained significantly associated with greater expectation of benefit from integrative therapies for pain (coef.=1.47, 95% CI, 0.67-2.27). Non-white race (coef.=1.04, 95% CI, 0.42-1.65), no college education (coef.=1.16, 95% CI, 0.59-1.74), and female gender (coef.=0.94, 95% CI, 0.38-1.50) were also associated with a greater expectation of benefit from integrative therapies. Pain management should be informed by a shared decision-making approach that aligns treatment expectancy with treatment selections to optimize outcomes. Compared with non-Hispanic participants, Hispanic individuals reported higher expectation of benefit from acupuncture and massage, highlighting the potential role for integrative therapies in addressing ethnic pain disparities. Trial Registration NCT02979574 NCT04095234.

Preventive service utilization among adults with cystic fibrosis covered by private insurance is comparable to the general population.

BACKGROUND: As the life expectancy of the cystic fibrosis (CF) population is lengthening with modulator therapies, diligent age-appropriate screening and preventive care are increasingly vital for long-term health and wellbeing. METHODS: We performed a retrospective analysis comparing rates of receiving age- and sex-appropriate preventive services by commercially insured adult people with CF (PwCF) and adults without CF from the general population (GP) via the Truven Health MarketScan database (2012-2018). RESULTS: We captured 25,369 adults with CF and 488,534 adults from the GP in the United States. Comparing these groups, we found that 43% versus 39% received an annual preventive visit, 28% versus 28% were screened for chlamydia, 38% versus 37% received pap smears every 3 years (21-29-year-old females), 33% versus 31% received pap smears every 5 years (30-64-year-old females), 55% versus 44% received mammograms, 23% versus 21% received colonoscopies, and 21% versus 20% received dyslipidemia screening (all screening rates expressed per 100 person-years). In age-stratified analysis, 18-27-year-old PwCF had a lower rate of annual preventive visits compared to adults in the same age group of the GP (27% versus 42%). CONCLUSIONS: We discovered a comparable-to-superior rate of preventive service utilization in adults with CF relative to the GP, except in young adulthood from 18-27 years. Our findings establish the importance of meeting the primary care needs of adults with CF and call for development of strategies to improve preventive service delivery to young adults.

Comparing sleep measures in cancer survivors: Self-reported sleep diary versus objective wearable sleep tracker.

Purpose: Cancer survivors are increasingly using wearable fitness trackers, but it's unclear if they match traditional self-reported sleep diaries. We aimed to compare sleep data from Fitbit and the Consensus Sleep Diary (CSD) in this group. Methods: We analyzed data from two randomized clinical trials, using both CSD and Fitbit to collect sleep outcomes: total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NWAK), time in bed (TIB) and sleep efficiency (SE). Insomnia severity was measured by Insomnia Severity Index (ISI). We used the Wilcoxon Singed Ranks Test, Spearman's rank correlation coefficients, and the Mann-Whitney Test to compare sleep outcomes and assess their ability to distinguish insomnia severity levels between CSD and Fitbit data. Results: Among 62 participants, compared to CSD, Fitbit recorded longer TST by an average of 14.6 (SD = 84.9) minutes, longer WASO by an average of 28.7 (SD = 40.5) minutes, more NWAK by an average of 16.7 (SD = 6.6) times per night, and higher SE by an average of 7.1% (SD = 14.4); but shorter TIB by an average of 24.4 (SD = 71.5) minutes. All the differences were statistically significant (all p < 0.05), except for TST (p = 0.38). Moderate correlations were found for TST (r = 0.41, p = 0.001) and TIB (r = 0.44, p < 0.001). Compared to no/mild insomnia group, participants with clinical insomnia reported more NWAK (p = 0.009) and lower SE (p = 0.029) as measured by CSD, but Fitbit outcomes didn't. Conclusions: TST was the only similar outcome between Fitbit and CSD. Our study highlights the advantages, disadvantages, and clinical utilization of sleep trackers in oncology.

Acupuncture improves certain aspects of sleep in hematopoietic stem cell transplantation patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: High-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) is associated with a high symptom burden including sleep disturbance. Here we present the results of a secondary analysis of a randomized, sham-controlled trial assessing the effect of acupuncture on sleep quality during HSCT. METHODS: Adult multiple myeloma patients undergoing inpatient and outpatient autologous HSCT were randomized and blinded to receive either true or sham acupuncture (by licensed acupuncturists) once daily for 5 days starting the day after chemotherapy. Sleep onset, total sleep time, sleep efficiency percentage and sleep-onset latency time were assessed using an actigraphy-based sleep monitor. A multivariate regression analysis was conducted to compare the average area-under-the-curve of five acupuncture intervention days for each sleep outcome between groups, adjusted by baseline score and inpatient or outpatient chemotherapy stratum. RESULTS: Over 32 months, 63 patients were enrolled. Participants undergoing true acupuncture experienced a significant improvement in sleep efficiency when compared to sham (-6.70, 95% CI -13.15, -0.25, p = 0.042). Subgroup analysis showed that the improvement was more prominent in the inpatient setting (-9.62, 95% CI -18.76, -0.47; p = 0.040). True acupuncture tended to improve wake time after sleep onset (WASO; -10.95, p = 0.054). Between-group differences in other sleep related variables were not statistically significant. CONCLUSION: Our data suggest that true acupuncture may improve certain aspects of sleep, including sleep efficiency and possibly WASO, in multiple myeloma patients undergoing HSCT. By studying patient reported outcomes in future larger scale studies, acupuncture's role in improving sleep quality during HSCT treatment could be further elucidated. TRIAL REGISTRATION NUMBER: NCT01811862 (ClinicalTrials.gov).

The relationship between anxiety and vaginal-related sexual health in postmenopausal breast cancer survivors on aromatase inhibitors therapies: a cross sectional study.

PURPOSE: Sexual health problems and anxiety are disruptive symptoms in breast cancer survivors; however, little is known about these symptoms in postmenopausal breast cancer survivors on aromatase inhibitors therapies. This study aimed to determine the relationship between anxiety and vaginal-related sexual health problems in this population. METHODS: We analyzed cross-sectional data from a cohort study of postmenopausal women breast cancer survivors receiving aromatase inhibitors. Vaginal-related sexual health problems were assessed with the Breast Cancer Prevention Trial Symptom Checklist. Anxiety was assessed with the anxiety subscale of the Hospital Anxiety and Depression Scale. We used multivariable logistic regression to evaluate relationship between anxiety and vaginal-related sexual health adjusted for clinical and sociodemographic variables. RESULTS: Among 974 patients, 305 (31.3%) reported anxiety and 403 (41.4%) had vaginal-related sexual health problems. Compared to those without anxiety, patients with borderline and clinically abnormal anxiety reported higher rates of vaginal-related sexual health problems (36.8% vs. 49% and 55.7% respectively, p < 0.001). In multivariate analyses adjusted for clinical and sociodemographic factors, abnormal anxiety was associated with a higher rate of vaginal-related sexual health problems, with adjusted odds ratios of 1.69 (95% CI 1.06-2.70, p = 0.03). Vaginal-related sexual health problems were more frequent among patients who were under 65 years of age, received Taxane-based chemotherapy, reported depression, and were married/living with a partner (p < 0.05). CONCLUSION: Among postmenopausal breast cancer survivors on aromatase inhibitors therapies, anxiety was significantly associated with vaginal-related sexual health problems. As treatments for sexual health problems are limited, results suggest that psychosocial interventions for anxiety could potentially be adapted to simultaneously address sexual health needs.

Effect of acupuncture versus usual care on sleep quality in cancer survivors with chronic pain: Secondary analysis of a randomized clinical trial.

BACKGROUND: Chronic pain negatively affects sleep; it is unclear whether pain relief from acupuncture contributes to sleep quality improvements in cancer survivors. This study aimed to evaluate the effect of acupuncture versus usual care on sleep quality among cancer survivors with comorbid sleep disturbance and chronic musculoskeletal pain. METHODS: Sleep outcome data from the Personalized Electroacupuncture Versus Auricular Acupuncture Comparative Effectiveness (PEACE) randomized clinical trial were analyzed. Electroacupuncture or auricular acupuncture was compared with usual care for sleep quality improvement over 10 weeks of treatment among cancer survivors with clinically significant sleep disturbance and chronic musculoskeletal pain at baseline. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) global score. RESULTS: Among 268 participants (mean [standard deviation (SD)] age, 61.4 [12.6] years; 191 women [71.3%]; mean [SD] baseline PSQI global score, 10.3 [3.3] points), electroacupuncture and auricular acupuncture resulted in greater reductions in the PSQI global score from baseline to 10 weeks in comparison with usual care: 1.42 points (95% confidence interval [CI], 0.45-2.38; p = .004) and 1.59 points (95% CI, 0.62-2.55; p = .001), respectively. The improvement in sleep quality for the acupuncture groups was sustained for 24 weeks from randomization. Furthermore, a greater proportion of patients in the electroacupuncture and auricular acupuncture groups had clinically meaningful improvement in sleep quality compared to the usual care group (41.0% and 42.9% vs. 21.4%; p = .044). CONCLUSIONS: Among cancer survivors with comorbid sleep disturbance and chronic pain, electroacupuncture and auricular acupuncture produced a clinically relevant and persistent improvement in sleep quality. These findings suggest that acupuncture may be an evidence-based nonpharmacologic intervention to improve sleep health for cancer survivors with pain. PLAIN LANGUAGE SUMMARY: This study analyzed the sleep quality data from a published randomized clinical trial that evaluated the effect of electroacupuncture or auricular acupuncture versus usual care on pain relief among people who survived cancer. This analysis included a prespecified subgroup of 268 participants with co-occurring sleep disturbance and chronic musculoskeletal pain at baseline and found that patients who used acupuncture for pain relief demonstrated greater improvements in sleep quality compared with patients who received usual care. Sleep quality improvement by acupuncture was sustained after the treatment ended.

Patient Characteristics Associated With Chemotherapy-Induced Peripheral Neuropathy Severity in a Phase II Clinical Trial: A Retrospective Analysis.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) can lead to chemotherapy dose reduction, delay, and discontinuation, and has limited effective prevention strategies. Our study aimed to identify patient characteristics associated with CIPN severity during weekly paclitaxel chemotherapy in people with early-stage breast cancer. METHODS: We retrospectively collected baseline data including participants' age, gender, race, body mass index (BMI), hemoglobin (regular and A1C), thyroid stimulating hormone, Vitamins (B6, B12, and D), anxiety, and depression up to 4 months prior to their first paclitaxel treatment. We also collected CIPN severity by Common Terminology Criteria for Adverse Events (CTCAE) after chemotherapy, chemotherapy relative dose density (RDI), disease recurrence, and mortality rate at the time of the analysis. Logistic regression was used for statistical analysis. RESULTS: We extracted 105 participants' baseline characteristics from electronic medical records. Baseline BMI was associated with CIPN severity (Odds Ratio [OR] 1.08; 95% CI, 1.01-1.16, P = .024). No significant correlations were observed in other covariates. At median follow-up (61 months), there were 12 (9.5%) breast cancer recurrences and six (5.7%) breast cancer-related deaths. Higher chemotherapy RDI was associated with improved disease-free survival (DFS, OR 1.025; 95% CI, 1.00-1.05; P = .028). CONCLUSIONS AND RELEVANCE: Baseline BMI may be a risk factor for CIPN and suboptimal chemotherapy delivery due to CIPN may negatively impact disease-free survival in patients with breast cancer. Further study is warranted to identify mitigating lifestyle factors to reduce incidences of CIPN during breast cancer treatment.

Addressing cancer-related fatigue through sleep: A secondary analysis of a randomized trial comparing acupuncture and cognitive behavioral therapy for insomnia.

Background: Fatigue is a troublesome symptom in cancer survivors that often results from disrupted sleep. We sought to assess whether two insomnia-focused non-pharmacological interventions are also effective for improving fatigue. Methods: We analyzed data from a randomized clinical trial comparing cognitive behavioral therapy for insomnia (CBT-I) versus acupuncture for insomnia among cancer survivors. Participants were 109 patients who reported insomnia and moderate or worse fatigue. Interventions were delivered over eight weeks. Fatigue was evaluated at baseline, week 8, and week 20 using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). We used both mediation analysis and t-tests to explore the extent to which fatigue reduction was attributable to insomnia response. Results: Compared to baseline, both CBT-I and acupuncture produced significant reductions in total MFSI-SF scores at week 8 (-17.1 points; 95% confidence interval [CI]: -21.1 to -13.1, and -13.2 points; 95% CI: -17.2 to -9.2, respectively, all p<0.001) and week 20 (-14.6 points; 95% CI: -18.6 to -10.6, and -14.2 points; 95% CI: -18.1 to -10.3. respectively, all p<0.001), with no significant between-group differences. MFSI-SF total scores at week 8 were significantly associated with sleep improvements in both CBT-I and acupuncture groups (p<0.001 and p=0.011, respectively). Insomnia responders demonstrated significantly greater improvements in mean MFSI-SF total scores compared with non-responders in the CBT-I group (p=0.016) but not in the acupuncture group. Conclusion: CBT-I and acupuncture produced similar, clinically meaningful, and durable fatigue reductions in cancer survivors with insomnia, primarily through improvements in sleep. Acupuncture may also reduce fatigue through additional pathways.

Impact of Baseline Expectancy on Outcome Prediction of Real and Sham Acupuncture for Persistent Chemotherapy-Induced Peripheral Neuropathy Pain in Solid Tumor Survivors: A Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) pain significantly worsens cancer survivors' quality of life. Expectancy may play an important role in acupuncture response. We sought to explore whether expectancy predicts pain outcome in real acupuncture (RA) and sham acupuncture (SA) in cancer survivors. METHODS: We analyzed data from a randomized clinical trial that evaluated the effect of RA on CIPN symptoms compared to SA and wait list control (WLC) in 75 cancer survivors. This secondary analysis was limited to CIPN pain measured by the Numeric Rating Scale (NRS), graded from 0 to 10. Interventions were delivered over 8 weeks. SA was implemented using a combination of non-acupuncture points and a non-insertion procedure. Patient expectancy was measured by the Acupuncture Expectancy Scale (AES) 3 times during the study. We used a linear regression model to evaluate if the NRS score was associated with the baseline AES score at the end of treatment (week 8), adjusting for baseline NRS score. RESULTS: AES was similar among 3 groups at baseline (RA: 11.8 ± 2.7; SA: 12.1 ± 3.8.; WLC: 14.6 ± 4.2; P = .062). Baseline AES was not found to be significantly associated with the week 8 NRS score among patients in all RA, SA, and WLC groups (all P > .05). However, we found a trend that higher baseline AES predicted lower NRS score at week 8 in the SA group: a one-point higher score on baseline expectancy was associated with a 0.3-point reduction in NRS pain score (P = .059) at week 8. CONCLUSIONS: The association of baseline expectancy and acupuncture response was similar between RA and SA. However, SA seemed to rely more on expectancy than RA. Further studies with larger sample sizes are needed to confirm this finding.

Feasibility of combining pelvic reconstruction with gynecologic oncology-related surgery.

INTRODUCTION AND HYPOTHESIS: At our institution, every patient seen by the gynecologic oncology service is screened for pelvic floor dysfunction. This study was aimed at determining if a combined surgical approach by gynecologic oncology and urogynecology services at our institution was feasible and safe for this patient population. METHODS: We performed a retrospective review of patients undergoing combined surgery by gynecologic oncology and urogynecology services at our institution from 2013 to 2021. Perioperative variables, postoperative adverse events, and long-term outcomes were assessed, and descriptive statistics were performed. RESULTS: From 20 December 2013 to 29 January 2021, a total of 102 patients underwent concurrent surgical repair of pelvic organ prolapse and/or stress urinary incontinence. Seventy-three patients (71.6%) had normal/benign pathologic conditions, and 29 (28.4%) had premalignant/malignant pathologic conditions. Ten patients (9.8%) had a postoperative complication, including reoperation for exposed midurethral sling (4.9%), urinary retention requiring midurethral sling release (2.9%), reoperation for hemoperitoneum (1.0%), and anemia requiring blood transfusion (1.0%). Nine complications occurred in patients with benign/normal pathologic conditions (12.3%), and one complication occurred in patients with pre-malignant/malignant pathologic conditions (3.4%). CONCLUSIONS: In our single-institution experience, concurrent gynecologic oncology and pelvic floor reconstructive surgery were safe and feasible in combination with no reported major morbidity events.

Does expectancy affect insomnia treatment response in cancer survivors receiving acupuncture and cognitive behavioral therapy?

PURPOSE: Insomnia negatively affects quality of life in cancer survivors. Expectations of insomnia treatment efficacy may influence response to intervention. We sought to determine whether pre-treatment outcome expectancy predicts response to two non-pharmacological interventions for insomnia among cancer survivors. METHODS: We analyzed data from a randomized clinical trial that compared acupuncture versus cognitive behavioral therapy for insomnia (CBT-I) in cancer survivors. Patient expectancy was measured by the Mao Treatment Expectancy Scale (MTES) at baseline. Insomnia severity was assessed using the Insomnia Severity Index (ISI) at treatment completion (week 8). Multivariate linear regression was used to evaluate the associations between pre-treatment expectancy and ISI score at week, 8 adjusting for co-variates. RESULTS: Expectancy for acupuncture and CBT-I were similar at baseline (acupuncture: 13.3 ± 4.0; CBT-I: 13.2 ± 2.9, p = 0.17). Greater baseline expectancy scores were associated with a greater and statistically significant insomnia severity reduction at week 8 in the acupuncture group (beta coefficients [Coef.] = - 0.35, 95% confidence interval [CI] = - 0.6 to - 0.1, p = 0.016) adjusted for co-variates. Baseline expectancy was not statistically associated with insomnia severity reduction in the CBT-I group (Coef. = - 0.2, 95% CI = - 0.7 to 0.2, p = 0.31). High expectancy was significantly associated with greater proportion of treatment responders at week 8 in the acupuncture group (76% vs. 38%, p = 0.001) but not in the CBT-I group (83% vs. 70%, p = 0.21). CONCLUSIONS: Higher pre-treatment outcome expectancy predicted significantly greater insomnia improvement in patients receiving acupuncture but not in those receiving CBT-I. IMPLICATIONS FOR CANCER SURVIVORS: Aligning treatment provision with expected outcomes may lead to personalized non-pharmacological insomnia management for cancer survivors.

Cystic fibrosis transmembrane conductance regulator modulators and the exocrine pancreas: A scoping review.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes. METHODS: We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included. RESULTS: Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values <200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7). CONCLUSIONS: CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.

Tibetan Herbal Pain-Relieving Plaster for Chronic Musculoskeletal Pain Among Cancer Survivors: Study Protocol of a Randomized, Double-Blind, Placebo-Controlled Trial.

Chronic pain is common and debilitating in cancer survivors. Tibetan herbal pain-relieving plaster is used as an external analgesic to treat musculoskeletal pain in China; however, its safety and efficacy have not been evaluated via clinical trials in cancer survivors. We designed this Phase II randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04916249) to assess the efficacy and safety of the pain-relieving plaster for temporary pain relief among cancer survivors with chronic musculoskeletal pain. Under ethical approval from the Institutional Review Board at the Memorial Sloan Kettering Cancer Center, we will enroll eligible cancer survivors who have a clinical diagnosis of moderate to severe chronic musculoskeletal pain in this study. We use a central randomization system to allocate the eligible participants to either the treatment or the control group in a 1:1 ratio, with stratification by baseline opioid use. We will instruct the participants to apply the herbal patch (Tibetree Pain-Relieving Plaster, Tibet Cheezheng Tibetan Medicine Co. Ltd., Tibet, China) or placebo patch daily at the focal area with worst pain for 14 consecutive days. Study physician, participant, outcome assessor, and biostatistician are blinded to the group allocation. The primary outcome is pain severity measured by the Brief Pain Inventory on Days 2-7. Secondary outcomes include changes in insomnia, anxiety, depression, fatigue, pressure pain threshold, pain medication use, and global impression of change. We will also monitor the adverse events throughout the study period. Statistical analysis will follow the intention-to-treat principle and linear mixed modeling will be used. With rigorous design and implementation, this randomized, placebo-controlled trial will provide the initial evidence on the efficacy and safety of the pain-relieving plaster for pain relief among cancer survivors with chronic musculoskeletal pain.

Cystic fibrosis patients on cystic fibrosis transmembrane conductance regulator modulators have a reduced incidence of cirrhosis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol. AIM: To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF. METHODS: A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups. RESULTS: A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients (P = 0.05), patients on Ursodiol (P < 0.001), and patients on dual therapy (P = 0.003). The highest incidence of cirrhosis was found among patients treated with Ursodiol alone, compared to untreated patients (P < 0.001) or patients on Ursodiol and CFTR modulators (P = 0.01). CONCLUSION: CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

Characterisation of PDGF-BB:PDGFRß signalling pathways in human brain pericytes: evidence of disruption in Alzheimer's disease.

Platelet-derived growth factor-BB (PDGF-BB):PDGF receptor-ß (PDGFRß) signalling in brain pericytes is critical to the development, maintenance and function of a healthy blood-brain barrier (BBB). Furthermore, BBB impairment and pericyte loss in Alzheimer's disease (AD) is well documented. We found that PDGF-BB:PDGFRß signalling components were altered in human AD brains, with a marked reduction in vascular PDGFB. We hypothesised that reduced PDGF-BB:PDGFRß signalling in pericytes may impact on the BBB. We therefore tested the effects of PDGF-BB on primary human brain pericytes in vitro to define pathways related to BBB function. Using pharmacological inhibitors, we dissected distinct aspects of the PDGF-BB response that are controlled by extracellular signal-regulated kinase (ERK) and Akt pathways. PDGF-BB promotes the proliferation of pericytes and protection from apoptosis through ERK signalling. In contrast, PDGF-BB:PDGFRß signalling through Akt augments pericyte-derived inflammatory secretions. It may therefore be possible to supplement PDGF-BB signalling to stabilise the cerebrovasculature in AD.

Platelet-derived growth factor signalling in neurovascular function and disease.

Platelet-derived growth factors are critical for cerebrovascular development and homeostasis. Abnormalities in this signalling pathway are implicated in neurological diseases, especially those where neurovascular dysfunction and neuroinflammation plays a prominent role in disease pathologies, such as stroke and Alzheimer's disease; the angiogenic nature of this pathway also draws its significance in brain malignancies such as glioblastoma where tumour angiogenesis is profuse. In this review, we provide an updated overview of the actions of the platelet-derived growth factors on neurovascular function, their role in the regulation of perivascular cell types expressing the cognate receptors, neurological diseases associated with aberrance in signalling, and highlight the clinical relevance and therapeutic potentials of this pathway for central nervous system diseases.