Nevin Manimala

J Cosmet Dermatol. 2023 Aug 26. doi: 10.1111/jocd.15970. Online ahead of print.

ABSTRACT

BACKGROUND: A previous injection algorithm termed the “Toxin Lift” was recently introduced and described volume increases in the midface following neuromodulator treatments of the jawline. Increase in midfacial volume due to soft tissue repositioning could also affect the severity of infraorbital hollows.

OBJECTIVE: The objective is therefore to evaluate whether the severity of infraorbital hollows can be improved by injecting neuromodulators in the supra-mandibular segment of the platysma.

MATERIALS AND METHODS: A total of 35 volunteers (11 males/24 females) with a mean age of 39.8 (9.6) years and a mean BMI of 25.2 (5.2) kg/m² were investigated. Bilateral infraorbital regions were evaluated via clinical assessment and semi-quantitative 3D imaging. The applied injection technique targeted the platysma via four injection points administering 5 I.U. per injection point resulting in a total of 20 I.U. per facial side.

RESULTS: Volume increase of the infraorbital region was 0.13 cc at 15 days (p = 0.001) and was 0.02 cc at 30 days (p = 0.452) whereas the skin displacement in cranial direction was 0.54 mm at 15 days (p < 0.001) and was 0.31 mm at 30 days (p < 0.001). Clinical evaluation revealed a highly statistically significant improvement of the tear trough, palpaebromalar groove, and of the lid-cheek junction when compared to baseline with all p < 0.001.

CONCLUSION: The results of this clinical prospective interventional analysis revealed that the “Toxin Lift” injection technique is capable to improve the clinical appearance of infraorbital hollows. The effects can be explained by the concepts of facial biomechanics.

PMID:37632259 | DOI:10.1111/jocd.15970

Perfusion. 2023 Aug 26:2676591231198366. doi: 10.1177/02676591231198366. Online ahead of print.

ABSTRACT

Targeted oxygen delivery during cardiopulmonary bypass (CPB) has received significant attention due to its influence on patient outcomes, especially in mitigating acute kidney injury. While it has gained popularity in select institutions, there remains a gap in establishing it globally across multiple centers. The purpose of this investigation was to describe the development of a quality improvement process of targeted oxygen delivery during CPB across hospitals throughout the United States. A systematic approach to utilize oxygen delivery index (DO₂i) as a key performance indicator within hospitals serviced by a national provider of perfusion services. The process included a review of the current literature on DO₂i, which yielded a target nadir value (272 mL/min/m²) and an area under the curve (DO₂i²⁷²AUC) cut off of 632. All data is displayed on a dashboard with results categorized across multiple levels from system-wide to individual clinician performance. From January 2020 through December 2022, DO₂i data from 91 hospitals and 11,165 coronary artery bypass graft procedures were collected. During this period the monthly proportion of DO₂i measurements above the target nadir DO₂i²⁷² ranged from 60.5% to 78.4% with a mean+/-SD of 70.8 +/- 4.2%. Binary logistic regression for the first 7 months following monthly DO₂i performance reporting has shown a statistically significant positive linear trend in the probability of achieving the target DO₂i²⁷² (p < .001), with a crude increase of approximately 7.8% for DO₂i²⁷²AUC, and a 73.8% success rate (p < .001). A survey was sent to all individuals measuring oxygen delivery during CPB to assess why a target DO₂i²⁷² could not be reached. The two most common responses were an ‘inability to improve CPB flow rates’ and ‘restrictive allogeneic red blood cell transfusion policies’. This study demonstrates that targeting a minimum level of oxygen delivery can serve as a key performance indicator during CPB using a structured quality improvement process.

PMID:37632252 | DOI:10.1177/02676591231198366

Acta Obstet Gynecol Scand. 2023 Aug 26. doi: 10.1111/aogs.14668. Online ahead of print.

ABSTRACT

INTRODUCTION: Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood may be. The aim of this study is to evaluate the long-term consequences of VLS diagnosed in childhood or adolescence.

MATERIAL AND METHODS: The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re-evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients’ experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens.

RESULTS: A total of 81 women participated, median age 29.0 years, median follow-up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check-ups. Forty-five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high-grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study.

CONCLUSIONS: Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow-up.

PMID:37632250 | DOI:10.1111/aogs.14668

Clin Transl Allergy. 2023 Aug;13(8):e12290. doi: 10.1002/clt2.12290.

ABSTRACT

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common and disabling disease. Assessments of IgE and C-reactive protein (CRP) are recommended in the diagnostic work-up, but the role and clinical relevance of these biomarkers are not well characterized. Moreover, it remains unknown if elevated levels of IgE or CRP are linked to CSU microRNA (miRNA) signatures or interleukin 31 (IL-31).

METHODS: We measured IgE and CRP serum levels in 47 CSU patients (and 45 healthy controls) and determined CSU disease activity using the urticaria activity score (UAS7). Expression levels of miR-155 and miR-221 were assessed by RT-PCR, and IL-31 levels were determined by ELISA.

RESULTS: Total IgE and CRP levels were independently increased in CSU patients. IgE and CRP levels were highest and lowest in patients with high and mild disease activity. IgE levels correlated with miR-155 levels, whereas CRP levels correlated with miR-221 levels. miR-155 and miR-221 were significantly overexpressed in CSU patients. ROC analyses linked miRNA-155 and CSU with a sensitivity of 79% and specificity of 87%, and miRNA-221 and CSU with a sensitivity of 75% and specificity of 91%. High CRP and miR-221 expression levels were linked to elevated levels of IgG anti-TPO and IL-31.

CONCLUSION: IgE and CRP are useful biomarkers for disease activity in CSU, with distinct miRNA profiles. High CRP and miR-221 levels may point to autoimmune CSU and a role for IL-31.

PMID:37632245 | DOI:10.1002/clt2.12290

Clin Transl Allergy. 2023 Aug;13(8):e12287. doi: 10.1002/clt2.12287.

ABSTRACT

BACKGROUND: The allergenicity of pollen of Poaceae family members is a well-known and confirmed fact. Using the data of component-resolved molecular diagnostics of allergy, we set a goal to establish the population and individual characteristics of sensitization to grass pollen and assess the patterns of its development.

METHODS: Multiplex allergy Alex² test results of 20,033 patients were used. In addition to descriptive statistics to uncover traits of the sensitized population, statistical inference was utilized to establish the conditional probability of sensitisation, the nature of links between allergens, and the most frequent combinations of allergens in individual patient profiles.

RESULTS: Sensitivity to grass pollen comprised 30.79% of the studied sample. Children accounted for 62.21%, adults-37.79%. Sensitisation to Phl p 1, Lol p 1, and Cyn d 1 was the most frequent in all age groups. Among them, Phl p 1 and Lol p 1 were the major ones. Phl p 2, Phl p 5.0101, and Phl p 6 were also responsible for primary sensitization; Phl p 5.0101 promoted the highest sIgE levels. A combination “Lol p 1-Phl p 1”, where Lol p 1 might play a leading role, was most frequent in individual profiles. Monosensitization to Phl p 2 was the second most frequent and Bayesian Network suggested its independent development. Monosensitization to Cyn d 1, especially among children, may indicate the impact of climate change, promoting the spread of the subtropical grasses to the temperate region.

CONCLUSIONS: Descriptive statistics and known clinical data coincide well with statistical inference results and can provide for new clinical insights.

PMID:37632241 | DOI:10.1002/clt2.12287

J Genet Couns. 2023 Aug 26. doi: 10.1002/jgc4.1774. Online ahead of print.

ABSTRACT

Genetic counseling (GC) following abnormal Down syndrome (DS) screening tests aims to ensure learning of complex medical concepts and discussion of counselees’ personal desires. Pre-GC use of electronic learning tools (e-learning tools) can facilitate GC sessions by allowing more time for dialogue rather than learning medical and genetic concepts, enabling greater focus on the counselee’s decisional, psychological, and personal needs. Few studies have investigated such tools for DS screening tests and those who have focused on screening uptake rather than abnormal results and implications. This study evaluated prenatal GC outcomes following implementation of an e-learning tool utilizing an educational animated movie for couples of varied ethnic backgrounds in northern Israel, with abnormal DS screening tests. E-learning tool impact was assessed as knowledge level, informed choices, satisfaction with the intervention and GC process, the state of anxiety and duration of the GC meeting. The 321 study participants were randomized to three groups: animation movie, booklet, and control. All participants had been asked to complete pre- and post-counseling questionnaires. Outcome scores were compared between the research groups. Results showed increased knowledge level in general among participants in the animation group; among minority participants, the highest knowledge level was in the animation group. Anxiety levels and informed choices were not statistically different among the groups. However, watching the animation, Jewish ethnicity, good level of genetic literacy, and academic degree were significant predictors of informed choice, and those who watched the animation were three times more likely to make an informed choice than the control group. Our findings suggest that this e-learning tool is efficient and acceptable for the general population. Special attention is needed for minorities with lower genetic literacy and education.

PMID:37632224 | DOI:10.1002/jgc4.1774

Hum Reprod. 2023 Aug 25:dead165. doi: 10.1093/humrep/dead165. Online ahead of print.

ABSTRACT

STUDY QUESTION: Can two prediction models developed using data from 1999 to 2009 accurately predict the cumulative probability of live birth per woman over multiple complete cycles of IVF in an updated UK cohort?

SUMMARY ANSWER: After being updated, the models were able to estimate individualized chances of cumulative live birth over multiple complete cycles of IVF with greater accuracy.

WHAT IS KNOWN ALREADY: The McLernon models were the first to predict cumulative live birth over multiple complete cycles of IVF. They were converted into an online calculator called OPIS (Outcome Prediction In Subfertility) which has 3000 users per month on average. A previous study externally validated the McLernon models using a Dutch prospective cohort containing data from 2011 to 2014. With changes in IVF practice over time, it is important that the McLernon models are externally validated on a more recent cohort of patients to ensure that predictions remain accurate.

STUDY DESIGN, SIZE, DURATION: A population-based cohort of 91 035 women undergoing IVF in the UK between January 2010 and December 2016 was used for external validation. Data on frozen embryo transfers associated with these complete IVF cycles conducted from 1 January 2017 to 31 December 2017 were also collected.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on IVF treatments were obtained from the Human Fertilisation and Embryology Authority (HFEA). The predictive performances of the McLernon models were evaluated in terms of discrimination and calibration. Discrimination was assessed using the c-statistic and calibration was assessed using calibration-in-the-large, calibration slope, and calibration plots. Where any model demonstrated poor calibration in the validation cohort, the models were updated using intercept recalibration, logistic recalibration, or model revision to improve model performance.

MAIN RESULTS AND THE ROLE OF CHANCE: Following exclusions, 91 035 women who underwent 144 734 complete cycles were included. The validation cohort had a similar distribution age profile to women in the development cohort. Live birth rates over all complete cycles of IVF per woman were higher in the validation cohort. After calibration assessment, both models required updating. The coefficients of the pre-treatment model were revised, and the updated model showed reasonable discrimination (c-statistic: 0.67, 95% CI: 0.66 to 0.68). After logistic recalibration, the post-treatment model showed good discrimination (c-statistic: 0.75, 95% CI: 0.74 to 0.76). As an example, in the updated pre-treatment model, a 32-year-old woman with 2 years of primary infertility has a 42% chance of having a live birth in the first complete ICSI cycle and a 77% chance over three complete cycles. In a couple with 2 years of primary male factor infertility where a 30-year-old woman has 15 oocytes collected in the first cycle, a single fresh blastocyst embryo transferred in the first cycle and spare embryos cryopreserved, the estimated chance of live birth provided by the post-treatment model is 46% in the first complete ICSI cycle and 81% over three complete cycles.

LIMITATIONS, REASONS FOR CAUTION: Two predictors from the original models, duration of infertility and previous pregnancy, which were not available in the recent HFEA dataset, were imputed using data from the older cohort used to develop the models. The HFEA dataset does not contain some other potentially important predictors, e.g. BMI, ethnicity, race, smoking and alcohol intake in women, as well as measures of ovarian reserve such as antral follicle count.

WIDER IMPLICATIONS OF THE FINDINGS: Both updated models show improved predictive ability and provide estimates which are more reflective of current practice and patient case mix. The updated OPIS tool can be used by clinicians to help shape couples’ expectations by informing them of their individualized chances of live birth over a sequence of multiple complete cycles of IVF.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by an Elphinstone scholarship scheme at the University of Aberdeen and Aberdeen Fertility Centre, University of Aberdeen. S.B. has a commitment of research funding from Merck. D.J.M. and M.B.R. declare support for the present manuscript from Elphinstone scholarship scheme at the University of Aberdeen and Assisted Reproduction Unit at Aberdeen Fertility Centre, University of Aberdeen. D.J.M. declares grants received by University of Aberdeen from NHS Grampian, The Meikle Foundation, and Chief Scientist Office in the past 3 years. D.J.M. declares receiving an honorarium for lectures from Merck. D.J.M. is Associate Editor of Human Reproduction Open and Statistical Advisor for Reproductive BioMed Online. S.B. declares royalties from Cambridge University Press for a book. S.B. declares receiving an honorarium for lectures from Merck, Organon, Ferring, Obstetric and Gynaecological Society of Singapore, and Taiwanese Society for Reproductive Medicine. S.B. has received support from Merck, ESHRE, and Ferring for attending meetings as speaker and is on the METAFOR and CAPRE Trials Data Monitoring Committee.

TRIAL REGISTRATION NUMBER: N/A.

PMID:37632223 | DOI:10.1093/humrep/dead165

Nephrol Dial Transplant. 2023 Aug 25:gfad183. doi: 10.1093/ndt/gfad183. Online ahead of print.

ABSTRACT

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are part of the standard of care for patients with chronic kidney disease (CKD), both with and without type 2 diabetes. Endothelin A (ETA) receptor antagonists have also been shown to slow progression of CKD. Differing mechanisms of action of SGLT2 and ETA receptor antagonists may enhance efficacy. We outline a study to evaluate the effect of combination zibotentan/dapagliflozin versus dapagliflozin alone on albuminuria and estimated glomerular filtration rate (eGFR).

METHODS: We conduct a double-blind, active-controlled, Phase 2b study to evaluate the efficacy and safety of ETA receptor antagonist zibotentan and SGLT2i dapagliflozin in a planned 415 adults with CKD (ZENITH-CKD). Participants are being randomized (1:2:2) to zibotentan 0.25 mg/dapagliflozin 10 mg QD, zibotentan 1.5 mg/dapagliflozin 10 mg QD, and dapagliflozin 10 mg QD alone, for 12 weeks followed by a 2-weeks off-treatment wash-out period. The primary endpoint is the change in log-transformed urinary albumin-to-creatinine ratio (UACR) from baseline to Week 12. Other outcomes include change in blood pressure from baseline to Week 12 and change in eGFR the study. The incidence of adverse events will be monitored. Study protocol defined events of special interest include changes in fluid-related measures (weight gain or B-type natriuretic peptide).

RESULTS: A total of 459 patients were randomized and received treatment in placebo/dapagliflozin (n = 181), zibotentan 0.25 mg/dapagliflozin (n = 94), and zibotentan 1.5 mg/dapagliflozin (n = 184). The mean age was 62.9 years, 30.0% were female and 66.4% were White. At baseline, the mean eGFR of the enrolled population was 47.0 mL/min/1.73 m2 and the geometric mean UACR was 532 mg/g.

CONCLUSION: This study evaluates the UACR lowering efficacy and safety of zibotentan with dapagliflozin as a potential new treatment for CKD. The study will provide information about an effective and safe zibotentan dose to be further investigated in a Phase 3 clinical outcome trial. Clinical Trial Registration Number: NCT04724837.

PMID:37632201 | DOI:10.1093/ndt/gfad183

Int J Gynaecol Obstet. 2023 Aug 25. doi: 10.1002/ijgo.15045. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess whether earlier administration of antibiotic prophylaxis after prelabor rupture of membranes (PROM) at term would decrease the incidence of maternal and neonatal infections.

METHODS: This is a retrospective cohort study comparing women with term PROM who were initiated antibiotic prophylaxis within or after 6 h, and within or after 12 h from PROM to delivery during January 2019 to December 2021. Women with term PROM receiving cephalosporin and without contraindications to vaginal delivery or confirmed or suspected infection were included in the study. The primary outcome was puerperal infection, which refers to the reproductive tract infection occurring within 42 days of delivery. The type of pharmacoeconomic evaluation was selected based on the results of compared effectiveness between the early group and the late group. Propensity-score matching (PSM) was used to adjust confounding. Subgroup and sensitivity analyses were used to verify the robustness of results.

RESULTS: We enrolled 5353 women with term PROM, including 4331 initiated with antibiotic within 6 h, 1022 after 6 h, 5077 within 12 h, and 276 after 12 h. After PSM, no significant difference was observed in the baseline characteristics of the groups. There was no statistical difference between antibiotic use within 6 h and after 6 h, or within 12 h and after 12 h, in puerperal infection (4.6% vs. 4.3%, P = 0.826; 2.9% vs. 4.6%, P = 0.471, respectively), total maternal infection, neonatal sepsis, and total neonatal infection. Cost-minimization analysis showed there was no significant difference between antibiotic use within 6 h and after 6 h, or within 12 h and after 12 h, in direct medical costs.

CONCLUSION: This study showed that there was no statistical difference in the efficacy and economy of antibiotic prophylaxis used within 6-12 h after rupture of membranes versus after 6-12 h in women with term PROM.

PMID:37632160 | DOI:10.1002/ijgo.15045

Int J Lab Hematol. 2023 Aug 25. doi: 10.1111/ijlh.14156. Online ahead of print.

ABSTRACT

BACKGROUND: Studies have shown that the quantification of circulating clonal plasma cells (cCPCs) in peripheral blood using flow cytometry could be used as a prognostic predictor of poor outcome in multiple myeloma (MM).

METHODS: In 66 newly diagnosed MM, cCPCs were quantified (cCPC%) and analysed for association with outcome and survival. Single-tube combined surface (CD45/CD19/CD138/CD38/CD56/CD27/CD81 as per availability) and cytoplasmic (kappa/lambda) staining was done using pre-titrated volumes of antibodies. In 26 patients, repeat cCPC% was assessed post-induction therapy. For association studies, treatment response has been taken as good (VGPR and above) and poor (PR and below). All statistical analyses were performed with SPSS software version 16.0.

RESULTS: There was no significant association between cCPC% at baseline with staging (p = 0.43), β₂ -microglobulin (p = 0.27) and albumin (p = 0.08). There was a significant difference between the pre-induction and post-induction cCPC% (p = 0.0001). The patients were segregated using a cut-off of ≥0.197 and <0.197 based on the median values of baseline cCPC%. The post-induction outcome was available for 47 patients among whom 33 (70%) had VGPR and above. There was a significant association between higher cCPC% at baseline with poor treatment response (p = 0.008). The median OS in the study patients was 42 (CI 28.14-43.03) months and the median PFS was 39 (CI 28.49-49.04) months. Higher cCPC% showed a lower median PFS (30 vs. 39 months) and OS (35 vs. 41 months) compared to lower cCPC% though it was not statistically significant.

CONCLUSION: Flow cytometric baseline cCPC% in newly diagnosed MM was associated with poor treatment response and survival.

PMID:37632156 | DOI:10.1111/ijlh.14156