Common Clinical Practice Research Articles

A-109 The impact of adjusting circulating calcium levels for changes in albumin

Abstract Background Correcting patients’ circulating calcium to albumin level is a common clinical practice to aid in the evaluation of calcium disorders. More recent studies have called into question the utility of the calculation relative to its ubiquity. The purpose of this study is to re-evaluate the practice of calcium adjustment and thus impact on the interpretation of calcium level. Methods Retrospective calcium and albumin levels performed and reported during May 2022 were retrieved. Reference intervals for both serum calcium and albumin were statistically derived using the Hoffman regression method following removal of outliers. Samples exhibiting hypoalbuminemia had their calcium adjusted using the formula (corrected calcium = (0.8 * (derived mean normal albumin - patient's albumin) + calcium). Patients who had their calcium levels adjusted were then compared to the currently in use reference interval to determine if their initial classification of calcium levels was impacted. Results Reported calcium and albumin results from a total of 1639 patients (712 males and 927 females) were obtained. Male patients, 137 (19%) were found to exhibit hypoalbuminemia and their calcium levels were adjusted with 15 patients (2% of total) had their initial calcium status change. 13 patients were reclassified from a state of hypocalcemia to normocalcemia (average increase in calcium levels was 0.9 mg/dL), while 2 patients were reclassified as being hypercalcemic. Among females, 151 (16%) found to exhibit hypoalbuminemia had their calcium levels adjusted with 12 patients (1.3% of total) having their initial calcium classification changed. 11 were reclassified from a state of hypocalcemia to normocalcemia (average increase in calcium levels was 0.89 mg/dL) and one patient was reclassified as hypercalcemic. There was no gender specific significant difference in the extent of required calcium adjustment (p= 0.92). Among the 474 black patients 88 (19%) exhibited hypoalbuminemia and mean calcium level of 9.51 mg/dL. Of those 88 patients, 4 were reclassified from a state of hypocalcemia to normocalcemia (average calcium increase of 0.96 mg/dL) and one patient status changed from normocalcemia to hypercalcemia. Furthermore, among the 1094 white patients, 191 (17%) exhibited hypoalbuminemia and had a mean calcium level of 9.38 mg/dL. Among the white patients, 21 (2%) changed from a state of hypocalcemia to normocalcemia (average calcium increase of 0.88 mg/dL). One patient changed from a state of normocalcemia to hypercalcemia. There was no significant racial difference in in the extent of required calcium adjustment (p=0.65). Conclusions The practice of adjusting calcium to account for albumin levels lead to changes in patients’ calcium status and thus likely to be of benefit in clinical management. There were no significant gender or racial differences in the relative proportion of changes in calcium status following albumin correction.

Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia.

A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated antibiotic treatment during influenza infection causes a fungal dysbiosis that drive lung eosinophilia and impair MRSA clearance. Finally, we evaluated three cohorts of hospitalized patients and found eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs thereby increasing the risk of developing a secondary bacterial infection.

The observational EURACAN prospective clinical registry dedicated to epithelioid hemangioendothelioma: The protocol of an international and collaborative effort on an ultra-rare entity.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease. Registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE. To improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern. Settings and participantsIt is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. VariablesFull details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methodsThe data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression. The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual.

Determination of Fertility Hormones and Adipokines by LC-MRM/MS Analysis.

Due to the increase in the rate of male and female infertility, assisted fertilization practices are currently adopted as valid support for couples unable to get pregnant. Analytical approaches for fertility hormone dosages are constantly being developed, following the technological progress of fertilization methods that have evolved for more than a century. Indeed, the analysis of fertility hormones in serum samples is a common clinical practice to check the fertility state, but absolute quantification of these hormones is a great challenge due to biological variability and low serum concentrations. Currently, ELISA (enzyme-linked immunosorbent assay) based methods are the most used analytical techniques to quantify hormones in blood in clinical settings. The current Article discusses the development of a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) to monitor multiple fertility hormones of a protein nature in a single chromatographic run, i.e., LH (luteinizing hormone), FSH (follicle-stimulating hormone), TSH (thyroid-stimulating hormone), AMH (anti-Müllerian hormone), adiponectin, ghrelin, leptin, glucagon, and obestatin. Particular attention has been paid to the AMH hormone, whose ELISA-based quantification is known to be controversial due to the poor reproducibility between the various kits used. For AMH, the internal standard method was used for the quantitative determination to compare mass spectrometry data to the ELISA assays performed by an accredited analysis laboratory on a cohort of samples from women aged between 18 and 60 years. The ability to monitor multiple transitions by LC-MRM/MS ensured both high specificity and high selectivity, which is necessary for the quantification of protein and steroid hormones, besides improvements in data reproducibility and reduced analysis times and costs.

Safinamide effect on sleep architecture of motor fluctuating Parkinson's disease patients: A polysomnographic rasagiline-controlled study

IntroductionSleep problems commonly occur in Parkinson's disease (PD) and significantly affect patients' quality of life. A possible effect on subjective sleep disturbances of monoamine oxidase-B inhibitors (MAOB-Is) has been described. MethodsThis prospective, observational, single-centre study involved 45 fluctuating PD patients complaining sleep problems as documented by the PD Sleep Scale -2nd version (PDSS-2 ≥18) starting rasagiline 1 mg/daily or safinamide 100 mg/daily, according to common clinical practice, and maintaining antiparkinsonian therapy unchanged. Polysomnography (PSG), sleep questionnaires (PDSS-2, Epworth Sleepiness Scale - ESS), and motor function were evaluated at baseline (T0) and after 4 months of treatment (T1). ResultsSafinamide was prescribed in thirty patients and rasagiline in fifteen patients. Both drugs induced a significant improvement in Movement Disorder Society Unified PD Rating Scale III scores. Patients treated with rasagiline showed a significant increase in stage 1 (N1) Non-REM sleep compared to T0, with no significant effects on sleep scales. Patients treated with safinamide showed a significant increase in stage 3 of Non-REM sleep and sleep efficiency and a reduction in the rate of periodic limb movements, matching a significant reduction in PDSS-2 and ESS scales compared to T0. ConclusionThis study showed that safinamide, in addition to having a significant effect on PD motor symptoms, like the other MAOB-Is, may exert a specific beneficial effect on subjective and objective sleep, probably driven by its dual mechanism of action, which involves both dopaminergic and glutamatergic neurotransmission.

Explaining International Trends in Mortality on Hemodialysis Through Changes in Hemodialysis Practices in the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Rationale & ObjectiveCase-mix adjusted hemodialysis mortality has decreased since 1998. Many factors that influence mortality may have contributed to this trend and these associations may differ by continental region. We studied changes in hemodialysis facility practices over time and their potential role in mediating changes in patient survival. Study DesignObservational prospective cohort study. Setting & ParticipantsAdult hemodialysis patients treated in hemodialysis 500 facilities participating in the Dialysis Outcomes Practice Patterns Study (DOPPS) between 1999 and 2015 in the US, Japan, and 4 four European countries: Germany, Italy, Spain, and UK. PredictorsFour practice measures at each facility: the percentages of patients with Kt/V>1.2, interdialytic weight gain [IDWG]<5.7%, phosphorus<6 mg/dL, and using AV fistulae. OutcomesPatient survival. Analytical ApproachMediation analyses, adjusted for case mix, were conducted using 3-year study phase as the exposure and facility practice measures as potential mediators. ResultsIn Europe, we observed a 13% improvement in overall case-mix adjusted survival per decade. Trends in facility practice measures, especially Kt/V and phosphorus, explained 10% improvement in case-mix survival per decade, representing 77% (10% explained of 13% improvement) of the observed improvement. In Japan, 73% of the observed 12%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially Kt/V and IDWG. In the US, 56% of the observed 47%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially AV fistula use and phosphorus control. LimitationsUnmeasured changes in the characteristics of the patient population over this period may confound the observed associations. ConclusionThe improvements in adjusted hemodialysis patient survival in Europe, Japan, and the US from 1999 to 2015 can be largely explained by improvements in specific facility practices. Future changes in patient survival may be responsive to further evolution in the implementation of common clinical practices.

Drug utilization evaluation of ceftazidime-avibactam in a tertiary care hospital

Background: The World Health Organization considers antimicrobial resistance a major global threat, and ceftazidime-avibactam (CAZ-AVI) is a treatment for multidrug-resistant Gram-negative infections. The FDA approved its use in 2015 for infections with limited treatment options. Methods: A retrospective study was conducted in a hospital in India to analyse the use of CAZ-AVI formulation in patients. Data was collected from electronic records and included information on patient demographics, clinical and microbiological profiles, antibiotic treatment, and patient outcomes for those in the ICU. Results: A total of 110 patients were included in the study. On assessing the results of this study, it was found that, the median age of population who received CAZ-AVI was 63 years and hypertension, diabetes mellitus were the common comorbidities present in the patients. Out of 110 subjects, 66 (60%) patients were started with a high-end antibiotic as an empirical therapy. While analysing the resistance pattern, it was found that 22 (20%) were resistant and 84 (76%) of the study subjects were sensitive to ceftazidime-avibactam. There was higher clinical success for BSI, CUTI, VAP amongst the indications of CAZ-AVI and combination of CAZ-AVI with aztreonam has given the most successful treatment outcome. The combination of CAZ-AVI with one or two high end antibiotics was observed as a common clinical practice. Conclusions: The analysis of results showed encouraging clinical cure rates. Our study results suggest that ceftazidime-avibactam could be an effective standard therapy for managing MDR Gram -negative organisms.

Cytoprotective Effect of Growth Factors Derived From Platelets on Corticosteroid-Treated Primary Anterior Cruciate Ligament-Derived Stromal Cells and Chondrocytes.

Background The use of corticosteroids, such as methylprednisolone, for pain management is a common clinical practice. However, it is well known that corticosteroids induce toxicity in anterior cruciate ligament (ACL)-derived stromal cells and chondrocytes. Growth factors from platelets have anti-inflammatory effects that can potentially limit the cytotoxic effects of corticosteroids. In this study, we explored the role of growth factors obtained from the OssinextTM kit (commercially available Wockhardt growth factor concentrate (GFC) kit) in recovering methylprednisolone-induced cell damage. Methodology Primary ACL-derived stromal cells and chondrocytes were isolated from human ligament tissue and articular cartilage, respectively, and characterized by immunophenotyping, gene expression analysis, and immunostaining. GFC obtained from OssinextTM kit was used for the experiments. The ACL-derived stromal cells and chondrocytes were treated with methylprednisolone, alone or in combination with GFC. Cell viability was measured by the neutral red uptake assay. Changes in cell morphology and collagen pattern were observed microscopically by H&E staining and immunostaining, respectively. Cell proliferation was assessed by cell migration assay, and the cell ultra-structure was analyzed using transmission electron microscopy. Results Methylprednisolone was found to induce cytotoxicity, altered cell morphology, reduced cell proliferation, and organelle damage in both ACL-derived stromal cells and chondrocytes. GFC obtained from the OssinextTM kit was able to restore cell viability and reverse the cell structure damages induced by methylprednisolone. GFC was found to recover and protect the cells, both when used in combination with steroids and when used after the steroid treatment. Conclusions The results indicate that GFC may be clinically beneficial when used in combination with steroids to mitigate their adverse effects.

Reconsidering the usefulness of long-term high-dose buprenorphine.

Buprenorphine has been successfully used for decades in the treatment of opioid use disorder, yet there are complexities to its use that warrant attention to maximize its utility. While the package insert of the combination product buprenorphine\naloxone continues to recommend a maximum dose of 16 mg daily for maintenance, the emergence of fentanyl and synthetic analogs in the current drug supply may be limiting the effectiveness of this standard dose. Many practitioners have embraced and appropriately implemented novel practices to mitigate the sequelae of our current crisis. It has become common clinical practice to stabilize patients with 24 - 32 mg of buprenorphine daily at treatment initiation. Many of these patients, however, are maintained on these high doses (>16 mg/d) indefinitely, even after prolonged stability. Although this may be a necessary strategy in the short term, there is little evidence to support its safety and efficacy, and these high doses may be exposing patients to more complications and side effects than standard doses. Commonly known side effects of buprenorphine that are likely dose-related include hyperhidrosis, sedation, decreased libido, constipation, and hypogonadism. There are also complications related to the active metabolite of buprenorphine (norbuprenorphine) which is a full agonist at the mu opioid receptor and does not have a ceiling on respiratory suppression. Such side effects can lead to medical morbidity as well as decreased medication adherence, and we, therefore, recommend that after a period of stabilization, practitioners consider a trial of decreasing the dose of buprenorphine toward standard dose recommendations. Some patients' path of recovery may never reach this stabilization phase (i.e., several months of adherence to medications, opioid abstinence, and other clinical indicators of stability). Side effects of buprenorphine may not have much salience when patients are struggling for survival and safety, but for those who are fortunate enough to advance in their recovery, the side effects become more problematic and can limit quality of life and adherence.

New policies on skin-to-skin contact warrant an oxytocin-based perspective on perinatal health care.

In 2023, the World Health Organization (WHO) published a Global Position Paper on Kangaroo Mother Care (KMC), which is applicable to all countries worldwide: from the moment of birth, every "small and sick" newborn should remain with mother in immediate and continuous skin-to-skin contact (SSC), receiving all required clinical care in that place. This was prompted by the startling results of a randomized controlled trial published in 2021: in which 1,609 infants receiving immediate SSC were compared with 1,602 controls that were separated from their mothers but otherwise received identical conventional state-of-the-art care. The intervention infants showed a 25% reduction in mortality after 28 days. The new WHO guidelines are a significant change from earlier guidance and common clinical practice. The author presents that separating mothers and babies is assumed to be "normal" (a paradigm) but actually puts newborns at increased risk for morbidity and mortality. The author presents arguments and ethical perspectives for a new perspective on what is "normal," keeping newborns with their mothers is the infant's physiological expectation and critical requirement for healthy development. The author reviews the scientific rationale for changing the paradigm, based on synchronous interactions of oxytocin on both mother and infant. This follows a critique of the new policies that highlights the role of immediate SSC. This critique strengthens the case for implementing the WHO guidelines on KMC for small and sick babies. System changes will be necessary in both obstetric and neonatal settings to ensure seamless perinatal care. Based on the role of oxytocin, the author identifies that many current routine care practices may actually contribute to stress and increased vulnerability to the newborn. WHO has actionable recommendations about family involvement and presence in newborn intensive care units. The concepts of resilience and vulnerability have specific definitions well known in perinatal care: the key outcome of care should be resilience rather than merely the absence of vulnerability. Newborns in all settings and contexts need us to re-evaluate our paradigms and adopt and implement the new WHO guidelines on KMC in perinatal care.

Ultra-fast detection of pathogens and protein biomarkers using a low-cost silicon plasmonic biosensing platform

In this paper, we report, for the first time to our knowledge, a new versatile and future proof diagnostic platform for diverse applications and heterogeneous biological targets. This platform relies on a plasmonic-augmented silicon photonic biochip to detect bacteria and protein biomarkers within minutes. To demonstrate the potential of this platform in diverse applications, we demonstrate the detection of two heterogeneous targets, the bacterium Escherichia coli (E. coli) and the molecule C-reactive protein (CRP) using a universal detection method. E. coli is one of the most commonly encountered bacterial pathogens involved in food monitoring, food born infections and water contamination applications, while CRP is a well-established disease severity indicator frequently used in common clinical practice. The biochip used is fully compatible with CMOS semiconductor manufacturing, while it hosts biosensors arrays for any combination of detection assays. Each biosensor exploits a 70 μm long aluminum plasmonic transducer within a silicon nitride waveguide-based Mach–Zehnder Interferometer. Each aluminum surface was silanized and biomodified with specific antibodies. Biosensing experiments revealed that CRP can be detected in diverse sample mediums, and E. coli detection was achieved in buffer at concentrations as low as 10 cells/ml within 13–25 min. The results are in good agreement with preceding numerical simulations. The modular nature of the reported biosensing platform makes it scalable and customizable, allowing nearly any combination of diagnostic tests targeting pathogens and proteins to be integrated on the same biochip for food quality monitoring, environmental monitoring, drug discovery and modern cell therapy manufacturing, or biomedical applications.

O-205 Dydrogesterone versus micronized vaginal progesterone for luteal phase support in hormone replacement therapy frozen embryo transfer cycles (REMODEL): an exploratory randomized controlled trial

Abstract Study question Is dydrogesterone (DYD) comparable to micronized vaginal progesterone (MVP) for luteal phase support (LPS) in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles? Summary answer Ongoing pregnancy rates (OPR) at 12 weeks’ gestation were comparable between the study group using DYD and the control group using MVP. What is known already Thanks to vitrification, the number of frozen embryo transfer cycles has significantly increased, prompting for a thorough optimization. Few studies have prospectively compared different progesterone regimens in artificial frozen embryo transfer cycles. Currently, MVP is most commonly used for LPS in this setting, but side effects such as vaginal discharge cannot be neglected. Dydrogesterone, a selective progesterone receptor agonist with a high oral bioavailability, could be considered due to its more patient-friendly administration. Two randomized controlled trials confirmed the non-inferiority of dydrogesterone to MVP for LPS in fresh cycles, but robust data on its use in HRT-FET cycles remain limited. Study design, size, duration An exploratory randomized controlled trial was conducted at a university hospital from October 2021 to September 2023. Subjects were randomly allocated 1:1 to the study group using DYD (10mg three times daily) for LPS or the control group using MVP (2x200mg twice daily), all performing FET in a HRT cycle. The primary outcome was ongoing pregnancy rate at 12 weeks (OPR). Secondary objectives included biochemical pregnancy loss, early pregnancy loss (EPL) and live birth rate. Participants/materials, setting, methods Patients under 41 years of age with a normal BMI undergoing a single blastocyst transfer in a HRT-FET cycle without endometrial abnormalities were eligible for inclusion. Patients who required more than 14 days of estradiol valerate priming (2mg three times daily) to achieve an endometrial thickness of at least 7 mm were not included. Of the 170 patients screened, 19 did not meet the randomization criteria and 3 withdrew after randomization. Main results and the role of chance Demographic characteristics such as age, BMI, cause of infertility and regular cycle were comparable between the study and control groups, as were the frozen transfer cycle characteristics. With three drop-outs after randomization, both a per-protocol (PP) and an intention-to-treat (ITT) analysis were performed for the primary outcome. According to the PP analysis, the OPR was 31.5% in the study group and 45.3% in the control group (p = 0.08, difference in proportions (%) -14, 95% CI: -39-11). The ITT analysis showed similar results (OPR 31.1% versus 44.2% in the study and control groups, respectively, p = 0.10). Multivariate regression adjusting for age, BMI, endometrial thickness and parity showed no significant association between the type of LPS administered and OPR (OR 1.92, 95% CI 0.95-3.86, p = 0.07). Positive hCG rates were comparable between both groups (58.9% versus 61.3% in the study and control groups, p = 0.76). Differences in biochemical pregnancy loss (14.0% versus 2.2% in the study and control groups, respectively, p = 0.05) and EPL (32.6% versus 23.9% in the study and control groups, respectively, p = 0.37) did not reach statistical significance. The live birth rate did not differ significantly between the two groups (26.8% versus 41.9%, p = 0.06), but the delivery outcome of 3 patients is missing to date. Limitations, reasons for caution Despite the randomized nature of the study, the exploratory design warrants cautious interpretation of the results due to the primary outcome’s insufficient statistical power. The dosages of the LPS medication used are based on common clinical practice, but due to the absence of dose-finding studies, this may impact the results. Wider implications of the findings The results, although not statistically significant, may raise clinical implications and call for larger studies. A forthcoming analysis will assess progesterone levels throughout the cycle in these study patients, examining their impact on pregnancy outcomes. Given differences in pharmacological profiles, various dosages may also be explored. Trial registration number NCT04758871

O-001 Human Reproduction Keynote lecture: Progesterone for pregnant people with threatened miscarriage

Abstract Threatened miscarriage, characterized by vaginal bleeding in early pregnancy, affects approximately 25% of all clinical pregnancies. Progesterone supplementation, typically administered vaginally, is a common clinical practice aimed at preventing miscarriage in cases of threatened miscarriage. However, the evidence regarding the effectiveness of this intervention is conflicting and subject to varying interpretations. In a randomized controlled trial conducted in Queensland, Australia, we evaluated the efficacy of nightly 400 mg vaginal progesterone administration, initiated at the onset of bleeding and continued until 12 weeks gestation, in increasing live birth rates among women experiencing threatened miscarriage. Our study did not find evidence supporting a treatment effect of vaginal progesterone in enhancing live birth rates, nor did we find evidence that progesterone improves live birth rates in women with a history of two or more previous miscarriages. We conclude that routine use of progesterone for threatened miscarriage cannot be recommended. However, the potential therapeutic benefit of progesterone in women with threatened miscarriage following recurrent pregnancy losses warrants further investigation through dedicated clinical trials in this population.

P-294 Intrauterine infusion of autologous platelet-rich plasma(PRP) for patients with refractory thin endometrium in euploid frozen embryo transfer cycles improve pregnancy outcomes

Abstract Study question Can intrauterine infusion of autologous platelet-rich plasma(PRP) for patients with refractory thin endometrium in euploid frozen embryo transfer(FET) cycles improve pregnancy outcomes? Summary answer Intrauterine infusion of autologous platelet-rich plasma(PRP) for patients with refractory thin endometrium in euploid FET cycles improve pregnancy outcomes. What is known already Previous studies have reported a positive correlation between endometrial thickness and pregnancy rate, which has led to the common clinical practice of canceling embryo transfer in cycles where the patient’s endometrial thickness remains below 7mm.One of the novel and promising treatments to improve pregnancy outcomes in patients with refractory thin endometrium is intrauterine infusion of autologous PRP.Recent studies demonstrated that intrauterine infusion of PRP improve pregnancy outcomes in these patients.Thus, to better assess the efficacy of intrauterine PRP treatment, further studies involving euploid embryos are necessary to rule out failed implantation or pregnancy loss due to aneuploidy of the embryos. Study design, size, duration This retrospective study analyzed all cycles(n = 131) of euploid FET in women with refractory thin endometrium at the CHA Fertility Center in Seoul Station from January 2022 to August 2023.Patients were divided into two groups according to whether they received PRP intrauterine infusion before embryo transfer in euploid FET cycles.Group A(n = 88) received intrauterine infusion of PRP at least once before transfer of euploid FET,and Group B(n = 43) underwent euploid FET without PRP infusion. Participants/materials, setting, methods Intrauterine infusion of autologous PRP was performed on patients who had more than two canceled FET cycles due to thin endometrial thickness(&amp;lt;7mm). Endometrial preparation was executed according to a standardized protocol for hormone replacement therapy. Group A received the last autologous PRP infusion 48 hours before euploid FET. PRP preparation was carried using an aseptic PRP centrifuge kit (PROSYS PRP; Prodizen, Korea). All embryos transferred were tested for genetic abnormalities using next-generation sequencing. Main results and the role of chance There was no significant difference in mean age and maximum endometrial thickness between the two groups. (38.1±3.1 vs. 38.3±3.2, p = 0.986 and 6.6±1.1 vs. 6.0±0.8, p = 0.320, respectively) Group A had significantly higher clinical pregnancy rates and ongoing pregnancy rates than Group B. (51.1% vs. 30.2%, p = 0.024 and 44.3 vs. 16.3%, p = 0.0017, respectively) Implantation rate and beta HCG positivity were also higher in group A, but there was no statistical difference. (63.6% vs. 46.5%, p = 0.063 and 37.2 vs. 23.2%, p = 0.064, respectively) Limitations, reasons for caution This is a retrospective study and results must be confirmed on a well-designed randomized controlled study. Also, follow-up study consisting of larger number of patients is necessary. Wider implications of the findings Autologous PRP intrauterine infusion has shown positive effects in assisting implantation in patients with refractory thin endometrium. In particular, euploid frozen embryo transfer in these patients excludes failed implantation and pregnancy loss due to embryo aneuploidy, suggesting that intrauterine PRP treatment contributes to successful implantation and pregnancy. Trial registration number not applicable

Impact of Upadacitinib on Atopic Keratoconjunctivitis Exacerbated by Dupilumab Treatment in Atopic Dermatitis Patients: A Prospective Dermatological and Ophthalmological Clinical Evaluation in Common Clinical Practice.

Introduction: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition with a substantial impact on patients, particularly due to ocular involvement known as atopic keratoconjunctivitis (AKC). Current therapeutic approaches, such as dupilumab, often lead to conjunctivitis, prompting exploration of alternative treatments like upadacitinib. Methods: We collected dermatological and ophthalmological prospective clinical evaluations of six adults with moderate-to-severe AD, undergoing treatment with upadacitinib after discontinuation of dupilumab due to the onset of AKC during therapy and the worsening of dermatitis in particular in the head and neck region. Clinical evaluations, including EASI scores, itch and sleep NRS, DLQI, and ocular parameters, were performed at baseline (during screening assessment before switching to upadacitinib) and then at week 12 and week 24. Clinical evaluation of AKC was performed by a team of ophthalmologists. Results: Upadacitinib not only improved atopic dermatitis in terms of EASI, itching, and sleep NRS, but also demonstrated a notable reduction in ocular signs and symptoms, as indicated by the Visual Analogue Scale (VAS), the Efron scale, and the Ocular Surface Disease Index Symptom Severity (OSDISS) scores. Discussion: Our observation of common clinical practice underscores the substantial impact of biological and small-molecule therapies on AD, emphasizing the limitation posed by dupilumab-associated conjunctivitis. Switching to upadacitinib significantly improved both clinical and functional ocular outcomes, suggesting its potential as an alternative therapeutic option for AD patients with ocular involvement. Conclusion: The presented data provides insights into the complex interplay between systemic therapies and ocular manifestations in AD. Upadacitinib emerges as a promising option to address dupilumab-associated conjunctivitis, offering improved quality of life for patients.

Diagnostic accuracy and clinical value of [68Ga]Ga-FAPI-46 PET/CT for staging patients with ovarian cancer: study protocol for a prospective clinical trial

Background[18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [18F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [18F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT and [18F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management.Methods and designFifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [18F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [68Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [18F]FDG PET/CT). Study subjects in Group B will undergo an additional [68Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [68Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting.DiscussionTo our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [68Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [68Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response.Trial registrationclinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.

The Effect of Anesthesia on Passive Ankle Dorsiflexion.

Equinus contractures can commonly be due to contractures of gastrocnemius muscle or combined contractures of the gastrocnemius-soleus Achilles tendon complex. The decision to release part or all of the gastrocnemius-soleus Achilles tendon complex is often assessed intraoperatively while the patient is under anesthesia. It remains unknown whether the administration of general anesthesia affects the measurement of passive ankle dorsiflexion. The unaffected, nonoperative limb on 46 foot and ankle patients underwent a Silfverskiold test measuring passive ankle dorsiflexion preoperatively and intraoperatively after administration of general anesthesia using an instrumented force-angular displacement goniometer. To determine clinical significance, we surveyed experienced surgeons to estimate the perceived minimally detectable clinical accuracy for measuring passive ankle dorsiflexion. Forty-six subjects were included with mean age of 42 ± 14.8 years, mean body mass index of 26.2 ± 4.9, and 52% female. The mean change in dorsiflexion values from before anesthesia to after the administration of general anesthesia was 1.9 degrees with 10 lb of pressure with knee extended (E10), 2.3 degrees with 20 lb of pressure with knee extended (E20), 2.8 degrees with 10 lb of pressure with knee flexed (F10), and 2.3 degrees with 20 lb of pressure with knee flexed (F20) (all P < .001). Thirty-three of 45 (73%) surgeons responded to the survey; all thought their minimally detectable clinical accuracy was 5 degrees or greater. After the administration of general anesthesia, a small but likely not clinically detectable increase in passive ankle dorsiflexion occurs. The common clinical practice of making intraoperative treatment decisions regarding the presence of a gastrocnemius-soleus driven equinus contractures after general anesthesia without use of paralytic agents appears reasonable given the magnitude of the changes identified in this study.

Osteoporosis management in Australian aged care facilities: a mixed method study

SummaryOsteoporosis is a common but sub-optimally managed disease amongst aged care residents. Pharmacists undertaking comprehensive medication reviews is one strategy to improve osteoporosis management. Analysis of pharmacist medication review recommendations has identified common clinical practice issues that can be addressed to optimise osteoporosis management for aged care residents.PurposeThis study investigates the prevalence of osteoporosis medicine use amongst Australian aged care residents and explores drug-related problems (DRPs) identified during medication reviews and pharmacist recommendations to resolve them.MethodsResident demographics, medications, diagnoses, osteoporosis related DRPs, and recommendations to resolve them were extracted from medication review reports. A mixed methods approach was taken to analysis, involving descriptive statistical analysis and content analysis.ResultsMedication review reports relating to 980 residents were collected. Antiresorptive therapies were used by 21.7% of residents, of which 87.2% were prescribed denosumab. Osteoporosis related DRPs represented 14.0% of all DRPs identified by pharmacists. Vitamin D was involved in 55.4% of these DRPs, the remainder concerned antiresorptive therapies (23.4%), medications contributing to osteoporosis (16.3%), and calcium (4.9%). Frequent deviations in practice from aged care clinical guidelines and consensus recommendations concerning vitamin D and calcium were found. DRPs and accompanying recommendations relating to denosumab revealed inadequate monitoring and inadvertent therapy disruptions.ConclusionPharmacist identified DRPs and recommendations revealed common aspects of clinical practice that can be addressed to improve osteoporosis management for aged care residents. A need to raise awareness of aged care-specific consensus recommendations concerning vitamin D and calcium is evident. Facility protocols and procedures must be developed and implemented to ensure safe and effective use of denosumab.

Developing a nomogram for estimating the risk of needing to perform a caesarean section after induction of labour in pregnancies using a COOK® Cervical Ripening Balloon.

Using a COOK® Cervical Ripening Balloon (CCRB) for cervical maturity has become a common clinical practice for the induction of labour (IOL). To develop and validate a predictive instrument that could estimate the risk of a caesarean after IOL in term pregnancies with CCRB treatment. The medical records of 415 pregnant women requiring IOL from January 2018 to October 2022 were retrospectively reviewed and randomly selected for training (290) and validation (125) sets in a 7:3 ratio. A model for predicting the risk of a caesarean was virtualised by a nomogram using logistic regression analysis. After completing the multivariate analysis, parity (odds ratio [OR] = 0.226; p= 0.017), modified Bishop score at induction (OR =0.688; p= 0.005) and the artificial rupture of membranes (OR = 0.436; p= 0.010) were identified as the predictors for implementing a caesarean delivery after IOL. The decision curve analysis showed that the model achieved a net benefit across all threshold probabilities. We successfully constructed a nomogram for caesarean delivery after IOL in pregnancies with CCRB treatment using factors including parity, modified Bishop score at induction and the artificial rupture of membrane.

Importance of the type of pharmacological treatment in patients with severe mental disorder

Introduction The use of long-acting treatments is a common clinical practice in psychiatry. No disease insight and the risk of treatment discontinuation in a significant portion of our patients, increase the demand for psychiatric emergency and hospital admissions. Treatment adherence must be facilitated, taking into account possible side effects and patient´s subjective satisfaction.Objectives-Evaluate the type of long-acting intramuscular treatment in selected patients. -Evaluate the differences in treatment satisfaction between different types of long-acting intramuscular treatments as well as frequency of psychiatric emergency and hospital admissions in the last year.MethodsWe select patients with different severe mental disorders who stay in a Medium Stay Unit, Sociosanitary Community Residence, Supervise house and Residence for the elderly in Albacete (Spain); all of them, with intramuscular neuroleptic treatment (zuclopenthixol dihydrochloride, aripiprazole long acting, palmitate paliperidone monthly, 3-monthly and 6-monthly) at least 1 year.We evaluate their sociodemographic characteristics, the satisfaction questionnaire with the treatment (TSQM-9) and the rate of psychiatric emergencies and admissions after current intramuscular treatment in last year.ResultsWe have selected 57 patients with an average age of 45.86. 78.94% with a diagnosis of schizophrenia, 12.28% with schizoaffective disorder, 5.26% bipolar disorder and 3.5% unspecified psychotic disorder.We can see in the graphics below that the longer duration of the intramuscular treatment, the greater satisfaction in all the items of the TSQM-9 questionnaire. 31% of the patients with zuclopenthixol dihydrochloride treatment, have gone to psychiatric emergencies and 28% of psychiatric admissions in the last year.18% of the patients with aripiprazole long acting, 17% with paliperidone palmitate long acting-monthly and 12% de 3-monthly have gone to psychiatric emergencies and 15%, 12% and 12% needed psychiatric admissions respectively. Patients with palmitate long acting-monthly have not emergencies or psychiatric admissions in the last year.Image:Image 2:Image 3:Conclusions- The longer long acting of the intramuscular treatments, the better patient satisfaction.- With the longer duration treatment (Palmitate paliperidone LD 6 month), we have lower psychiatric emergencies and hospital admissions.Disclosure of InterestNone Declared