bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of PrabotulinumtoxinA in Subjects With Benign Masseteric Hypertrophy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase 3 Trial and Open-Label Extension Study
Authors: Seok Joon , Koh Young Gue , Hong Jun Ki , Yun So Hye , Kim Da Hye , Son Hyung Seok , Choi Sun Young , Yoo Kwang Ho , Lee Yang Won , Kim Beom Joon 
Published: March 2024

BACKGROUND
Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option.

OBJECTIVE
We report the efficacy and safety for BTX in MMH over a period of 48 weeks.

METHODS
In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 (n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study.

RESULTS
The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed.

CONCLUSION
PrabotulinumtoxinA could effectively ameliorate MMH without major complications.
Effectiveness of head-mounted ultrasound display for radial arterial catheterisation in paediatric patients by anaesthesiology trainees
Authors: Kim Jin-Tae , Park Jung-Bin , Kang Pyoyoon , Ji Sang-Hwan , Kim Eun-Hee , Lee Ji-Hyun , Kim Hee-Soo , Jang. Young-Eun 
Published: March 2024

BACKGROUND
The effectiveness of head mounted real-time ultrasound displays (hereafter referred to as ‘smart glasses’) in improving hand-eye coordination in less experienced individuals, such as trainees in anaesthesia, is unclear.

OBJECTIVES
To compare the first-attempt success rate of smart glasses-assisted ultrasound-guided paediatric radial artery catheterisation with conventional ultrasound guided catheterisation performed by anaesthesiology trainees.

DESIGN
Prospective randomised controlled trial

SETTINGS
Tertiary university hospital from September 2021 to February 2023.

PATIENTS
One hundred and twenty-two paediatric patients (age <7 years, weight ≥3 kg) who required radial artery cannulation during general anaesthesia.

INTERVENTIONS
The participants were randomly assigned to either the ultrasound screen group (control) or the smart glasses group prior to radial artery catheterisation.

MAIN OUTCOME MEASURES
The primary outcome was the first attempt success rate. Secondary outcomes included the number of attempts, use of transfixion technique, overall complication rate, and clinical anaesthesiology (CA) year of the operators.

RESULTS
A total of 119 paediatric patients were included in the analysis. The smart glasses group exhibited higher first-attempt success rate than did the control group (89.8% [53/59] vs. 71.7% [43/60]; P = 0.023; odds ratio (OR) 3.49; (95% confidence interval (CI) 1.27–9.6). The overall number of attempts [median, 1; interquartile range (IQR), 1–1; range, 1–3 vs. median, 1; IQR, 1–2; range, 1–4; P
= 0.006], use of transfixion technique (12/59 [20.3%] vs. 28/60 [46.7%]; P = 0.002), and overall complication rate (6.8% [4/59] vs. 30.0% [18/60]; P = 0.002) were lower in the smart glasses group than in the control group. However, among paediatric anaesthesiology fellows (CA 5 years), the first- (89.3% [25/28] vs. 80.8% [21/26]; P = 0.619) and second-attempt success rates (96.4% [27/28] vs. 80.8% [21/26]; P = 0.163) did not differ between the two groups.

CONCLUSIONS
Smart glasses-assisted ultrasound guided radial artery catheterisation improved the first attempt success rate among anaesthesiology trainees, reducing the number of attempts and overall complication rates in small paediatric patients. Smart glasses were more effective for anaesthesia residents (CA 2–4 years) but were not effective for paediatric anaesthesiology fellows (CA 5 years).

TRIAL REGISTRATION
ClinicalTrials.gov (NCT05030649; registered 1 September 2021; principal investigator, Prof. Jin-Tae Kim) (https://classic.clinicaltrials.gov/ct2/show/NCT05030649).
Rapid in vivo evaluation system for cholestasis-related genes in mice with humanized bile acid profiles
Authors: Wakasa Kihiro , Tamura Ryutaro , Osaka Shuhei , Takei Hajime , Asai Akihiro , Nittono Hiroshi , Kusuhara Hiroyuki , Hayashi Hisamitsu 
Published: March 2024

Background:Pediatric cholestatic liver diseases (Ped-CLD) comprise many ultrarare disorders with a genetic basis. Pharmacologic therapy for severe cases of Ped-CLD has not been established. Species differences in bile acid (BA) metabolism between humans and rodents contribute to the lack of phenocopy of patients with Ped-CLD in rodents and hinder the development of therapeutic strategies. We aimed to establish an efficientin vivosystem to understand BA-related pathogenesis, such as Ped-CLD.Methods:We generated mice that express spCas9 specifically in the liver (L-Cas9Tg/Tg[liver-specific Cas9Tg/Tg] mice) and designed recombinant adeno-associated virus serotype 8 encoding small-guide RNA (AAV8 sgRNA) targetingAbcc2,Abcb11, andCyp2c70. In humans,ABCC2andABCB11deficiencies cause constitutional hyperbilirubinemia and most severe Ped-CLD, respectively.Cyp2c70encodes an enzyme responsible for the rodent-specific BA profile. Six-week-old L-Cas9Tg/Tgmice were injected with this AAV8 sgRNA and subjected to biochemical and histological analysis.Results:Fourteen days after the injection with AAV8 sgRNA targetingAbcc2, L-Cas9Tg/Tgmice exhibited jaundice and phenocopied patients withABCC2deficiency. L-Cas9Tg/Tgmice injected with AAV8 sgRNA targetingAbcb11showed hepatomegaly and cholestasis without histological evidence of liver injury. Compared toAbcb11alone, simultaneous injection of AAV8 sgRNA forAbcb11andCyp2c70humanized the BA profile and caused higher transaminase levels and parenchymal necrosis, resembling phenotypes withABCB11deficiency.Conclusions:This study provides proof of concept for efficientin vivoassessment of cholestasis-related genes in humanized bile acid profiles. Our platform offers a more time- and cost-effective alternative to conventional genetically engineered mice, increasing our understanding of BA-related pathogenesis such as Ped-CLD and expanding the potential for translational research.
Rectal Sparing Approach after preoperative Radio- and/or Chemo-therapy (ReSARCh): a prospective, multicenter, observational study
Authors: Spolverato Gaya , Bao Quoc Riccardo , Delrio Paolo , Guerrieri Mario , Ortenzi Monica , Cillara Nicola , Restivo Angelo , Deidda Simona , Spinelli Antonino , Romano Carmela , Bianco Francesco , Sarzo Giacomo , Morpurgo Emilio , Belluco Claudio , Palazzari Elisa , Chiloiro Giuditta , Meldolesi Elisa , Coco Claudio , Pafundi Donato P. , Feleppa Cosimo , Aschele Carlo , Bonomo Michele , Muratore Andrea , Mellano Alfredo , Chiaulon Germana , Crimì Filippo , Maretto Isacco , Perin Alessandro , Urso Emanuele D.L. , Scarpa Marco , Bigon Mariasole , Scognamiglio Federico , Bergamo Francesca , Del Bianco Paola , Gambacorta Maria Antonietta , Rega Daniela , Pucciarelli Salvatore 
Published: March 2024

Background:
Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer; however, their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes.

Methods:
This prospective, multicenter, observational study investigated the outcomes of patients with clinical stage II–III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of 2 years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at 3 years.

Results:
Of the 178 patients enrolled in 16 centers, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6–45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall survival, disease-free survival, local recurrence-free survival, and distant recurrence-free survival was 80.6% (95% CI 73.9–85.8), 97.6% (95% CI 93.6–99.1), 90.0% (95% CI 84.3–93.7), 94.7% (95% CI 90.1–97.2), and 94.6% (95% CI 89.9–97.2), respectively. The 3-year stoma-free survival was 95.0% (95% CI 89.5–97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95% CI 59.9–81.2).

Conclusions:
In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromising the outcomes.
Vulvar Lichenoid Dermatoses With Emphasis on the Distinction Between Lichen Sclerosus and Lichen Planus: A 10-Year Study
Authors: D'Souza Sueallen Lorna , Ravikumar Gayatri , Antony Meryl , Tirumale Rajalakshmi 
Published: March 2024

Objectives
Lichen planus (LP) and lichen sclerosus (LS) are the most common vulvar lichenoid dermatoses. The diagnostic challenges are due to site-specific variation in microscopic appearance and small-sized biopsies. Authentication of diagnostic criteria to distinguish LS and LP to uncover any resemblance or divergence in presentation of these conditions is attempted.

Methods
Cases of vulvar LP and LS diagnosed between January 2012 to December 2022 were included. The clinical details included age, presenting symptoms, examination findings, and other organ involvement. Histopathological analysis of epidermal, dermal, and adnexal findings was done.

Results
There were 28 cases of vulvar LP and 72 cases of LS, with a median age of 51 and 60 years, respectively. Depigmentation and atrophy were the major clinical features in LS, whereas ulcers/erosions and erythema were more prevalent in LP with a significantly higher incidence of oral involvement. The most diagnostic feature in LS was diffuse dermal sclerosis (76.8%) and interstitial pattern of inflammation (81.4%), whereas the characteristic features in LP cases was a lichenoid pattern of inflammation (85.7%), necrotic keratinocytes, and lymphocytic exocytosis. In 44.4% of LS, unconventional features like compact orthokeratosis, parakeratosis, thickened/wedge-shaped hypergranulosis, and sawtooth rete pegs were noted. Lichen sclerosus with lichenoid inflammation (21.4%) mimicked LP, from which it was distinguished by presence of thickened or diminished granular layer with basal melanin absence (60%) and dermal homogenization (80%).

Conclusion
Although the classical, well-established variant of LS poses no diagnostic difficulty, the unconventional variant may mimic LP. Identification of the subtle histological clues demonstrated in this study can help to arrive at the correct diagnosis.
Attitudes Toward Proactive Topical Corticosteroid Use Among Women With Vulval Lichen Sclerosus
Authors: Rees Sophie , Arnold Susanne , Kherlopian Ashod , Fischer Gayle 
Published: March 2024

Objectives
Some practitioners are adopting proactive topical corticosteroid (TCS) therapy for vulval lichen sclerosus (VLS). We sought to understand patient attitudes toward proactive TCS therapy for VLS in a context in which proactive therapy is adopted.

Methods
Four online focus group discussions with 12 participants. Data analysis was informed by social constructionist grounded theory.

Results
All participants had accepted a proactive regimen. Three themes were developed from the analysis: “Coming to accept proactive therapy,” “Motivators to maintaining a proactive regimen,” and “The importance of a routine that fits me.” Within each theme are subthemes illustrating different dimensions of the theme.

Conclusions
Accepting proactive TCS therapy for VLS requires incorporating regular TCS use into a patient's identity, unlearning previous understandings regarding the safety of long-term TCS use, and adopting a regimen that fits within patients' lives and minimizes the loss of autonomy.
Incidence and Risk Factors for Recurrence and Progression of HPV–Independent Vulvar Intraepithelial Neoplasia
Authors: Voss Féline O. , van Beurden Marc , Veelders Koen J. , Bruggink Annette H. , Steenbergen Renske D.M. , Berkhof Johannes , Bleeker Maaike C.G. 
Published: March 2024

Objectives
Human papillomavirus (HPV)–independent vulvar intraepithelial neoplasia (VIN) is a rare yet aggressive precursor lesion of vulvar cancer. Our objectives were to estimate its long-term incidence, the risk of recurrent disease and progression to vulvar cancer, and risk factors thereof.

Materials and Methods
Patients with HPV-independent VIN between 1991 and 2019 in a selected region were identified from the Dutch Nationwide Pathology Databank (Palga). Data were collected from the pathology reports. Crude and European age-standardized incidence rates were calculated for 10-year periods. Kaplan-Meier analyses were performed to determine the cumulative recurrence and cancer incidence, followed by Cox regression analyses to identify associated risk factors.

Results
A total of 114 patients were diagnosed with solitary HPV-independent VIN without prior or concurrent vulvar cancer. The European age-standardized incidence rate increased from 0.09 to 0.69 per 100,000 women-years between 1991–2010 and 2011–2019. A cumulative recurrence and cancer incidence of 29% and 46% were found after 8 and 13 years of follow-up, respectively. Nonradical surgery was identified as the only independent risk factor for recurrent HPV-independent VIN. Risk factors associated with progression to cancer were increasing age and a mutant p53 immunohistochemical staining pattern.

Conclusions
The incidence of detected HPV-independent VIN has substantially increased the last decade and the subsequent recurrence and vulvar cancer risks are high. Although HPV-independent VIN may present as a wide morphologic spectrum, surgical treatment should aim for negative resection margins followed by close surveillance, especially for p53 mutant lesions.
Risk Factors for Lichen Sclerosus: A Case-Control Study of 43,000 Finnish Women
Authors: Halonen Pia , Heikinheimo Oskari , Hadkhale Kishor , Gissler Mika , Pukkala Eero , Jakobsson Maija 
Published: March 2024

Objectives
Lichen sclerosus (LS) is an inflammatory skin disease probably arising from an interplay of genetics, local irritation, and autoimmune processes. We identified potential risk factors for the disease using data from nationwide Finnish registries.

Methods
We identified all women diagnosed with LS within specialized health care during 1998–2016 (n = 10,692) and selected 3 age-matched population control women for each case. We calculated odds ratios (ORs) for possible risk factors using conditional logistic regression.

Results
Dermatological autoimmune conditions were strongly associated with LS (OR = 15.1, 95% confidence interval [CI] = 13.6–16.7 for morphea; OR = 10.3, 95% CI = 5.02–19.0 for lichen planus; OR = 6.86, 95% CI = 5.65–8.33 for alopecia; OR = 2.20, 95% CI = 1.88–2.56 for vitiligo). A diagnosis of Crohn or celiac disease increased the odds of LS (OR = 1.80, 95% CI = 1.71–1.89; OR = 1.49, 95% CI = 1.28–1.73, respectively) as did urge and stress incontinence (OR = 1.79, 95% CI = 1.71–1.87; OR = 1.28, 95% CI = 1.22–1.35, respectively).
The odds of LS were lower in women after a diagnosis of type 1 diabetes (OR = 0.43, 95% CI = 0.41–0.45), coronary artery disease (OR = 0.41, 95% CI = 0.38–0.43), and rheumatoid arthritis (OR = 0.38, 95% CI = 0.36–0.41).
Parous women had higher odds of LS (OR = 1.11, 95% CI = 1.04–1.17) than nulliparous ones, but increasing number of births decreased the risk. Lichen sclerosus was not associated with socioeconomic status nor the urbanicity level of the place of residence.

Conclusions
Certain autoimmune diseases and urinary incontinence were associated with LS.
Psychedelic Therapy: A Primer for Primary Care Clinicians—Ketamine
Authors: Evans Viviana D. , Arenas Alejandro , Shinozuka Kenneth , Tabaac Burton J. , Beutler Bryce D. , Cherian Kirsten , Fasano Chelsey , Muir Owen S. 
Published: March 2024

Background:Ketamine, an arylcyclohexylamine dissociative anesthetic agent, has evolved into a versatile therapeutic. It has a rapid-onset, well-understood cardiovascular effects and a favorable safety profile in clinical use. Its enantiomeric compound, esketamine, was approved by the Food and Drug Administration in 2019 for both treatment-resistant depression and major depressive disorder with suicidal ideation.Areas of Uncertainty:Research indicates dose-dependent impacts on cognition, particularly affecting episodic and working memory following both acute administration and chronic use, albeit temporarily for the former and potentially persistent for the latter. Alongside acute risks to cardiovascular stability, ketamine use poses potential liver toxicity concerns, especially with prolonged or repeated exposure within short time frames. The drug's association with “ketamine cystitis,” characterized by bladder inflammation, adds to its profile of physiological risks.Therapeutic Advances:Data demonstrate a single intravenous infusion of ketamine exhibits antidepressant effects within hours (weighted effect size averages of depression scores (N = 518) following a single 0.5 mg/kg infusion of ketamine isd= 0.96 at 24 hours). Ketamine is also effective at reducing posttraumatic stress disorder (PTSD) symptom severity following repeated infusions (Clinician-Administered PTSD Scale scores: −11.88 points compared with midazolam control). Ketamine also decreased suicidal ideation in emergency settings (Scale for Suicidal Ideation scores: −4.96 compared with midazolam control). Through its opioid-sparing effect, ketamine has revolutionized postoperative pain management by reducing analgesic consumption and enhancing recovery.Limitations:Many studies indicate that ketamine's therapeutic effects may subside within weeks. Repeated administrations, given multiple times per week, are often required to sustain decreases in suicidality and depressive symptoms.Conclusions:Ketamine's comprehensive clinical profile, combined with its robust effects on depression, suicidal ideation, PTSD, chronic pain, and other psychiatric conditions, positions it as a substantial contender for transformative therapeutic application.
Psychedelic Therapy: A Primer for Primary Care Clinicians—N,N-Dimethyltryptamine and Ayahuasca
Authors: Shinozuka Kenneth , Tabaac Burton J. , Arenas Alejandro , Beutler Bryce D. , Cherian Kirsten , Evans Viviana D. , Fasano Chelsey , Muir Owen S. 
Published: March 2024

Background:

N,N-dimethyltryptamine (DMT) is a naturally occurring serotonergic psychedelic found in natural plants around the globe. As the main psychoactive component in ayahuasca, which also contains monoamine oxidase inhibitors, DMT has been consumed as plant-based brew by indigenous peoples for centuries. Further research is required to delineate the therapeutic utility of DMT.

Areas of Uncertainty:
Although previous research has shown that DMT is synthesized endogenously, it may not be produced at physiologically relevant concentrations. Additionally, the phenomenological similarities between the DMT-induced state and near-death experiences led to the popular hypothesis that endogenous DMT is released during the dying process. However, this hypothesis continues to be debated. Generally, DMT and ayahuasca seem to be physiologically and psychiatrically safe, although ayahuasca is known to cause transient vomiting.

Therapeutic Advances:
A double-blind, randomized controlled trial showed that, within 1 week, ayahuasca causes remission in 36% of patients with treatment-resistant depression. According to top-line results from a recent phase IIa trial, 57% of patients with major depressive disorder experienced remission 12 weeks after receiving a single intravenous dose of DMT.

Limitations:
There has only been a single published double-blind randomized controlled trial on ayahuasca and 2 on DMT. All clinical trials have had small sample sizes (≤34 participants). DMT requires further research to understand its therapeutic and clinical potential as a psychedelic.

Conclusions:
Preliminary evidence indicates that ayahuasca and DMT may be more effective than existing antidepressants for treating major depressive disorder and treatment-resistant depression.
Hypokalemia in a young man…think Bartter syndrome type 3
Authors: Hamsho Suaad , Alhussen Abdul Hadi Daher , Alabdullah Hadi , Sleiay Bilal , Kasem Noor , Hassan Qussai 
Published: March 2024

Background:
Bartter syndrome is an autosomal recessive salt reabsorption disorder that results in decreased extracellular fluid volume with low/normal blood pressure.

Case presentation:
A 17-year-old boy with polydipsia, polyuria, weakness in the lower limbs, and ataxic gait. His Laboratory test shows hypokalemia; hypochloremia, hypomagnesemia and metabolic alkalosis. The authors’ patient was managed by fluid and electrolyte replacement, which is essential in emergency management.

Conclusion:
Bartter syndrome is difficult to treat, and currently, there is no complete cure. The overall prognosis depends on the extent of receptor dysfunction, and despite these facts, most patients can live a normal life if they strictly follow their treatment plan.