bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Botulinum Toxin in the Management of Hidradenitis Suppurativa: A Systematic Review
Authors: Geoghegan Luke , Rodrigues Raina , Harrison Conrad J. , Rodrigues Jeremy N. 
Published: July 2023

Background:
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by suppurative infection, sinus tract, and abscess formation. International management guidelines are largely consensus-based. Botulinum toxin (BTX) has been widely used in the treatment of apocrine and eccrine gland disorders, such as hyperhidrosis, although the effectiveness of BTX in the treatment of HS remains unknown. The aim of this systematic review was to understand the published evidence of BTX safety and effectiveness in the management of HS.

Methods:
We conducted a PRISMA-compliant, prospectively registered (PROSPERO, CRD42021228732), systematic review. We devised bespoke search strategy and applied it to the Cochrane Central Register of Controlled Trials, Medline, Embase, and OpenGrey up until March 2022. We included all clinical studies that reported outcomes following BTX treatment in patients diagnosed with HS (both adult and pediatric).

Results:
A total of 4658 studies were identified, of which six met full inclusion criteria reporting data on 26 patients. The six identified studies included one randomized control trial, one case series, and four case studies. The one included randomized control trial demonstrated a significant reduction in the Dermatology Life Quality Index score at 3 months following treatment with BTX.

Conclusions:
The effectiveness and safety of BTX in the treatment of HS remain unknown. This systematic review identified a paucity of high-quality clinical data. Evidence of treatment effectiveness is likely to come from registry-based cohort studies using established core outcome sets in the first instance.
Role of nonneoplastic PVT in the natural history of patients with cirrhosis and first diagnosis of HCC
Authors: Senzolo Marco , Shalaby Sarah , Grasso Marco , Vitale Alessandro , Pizzirani Enrico , Barbiero Giulio , Zanetto Alberto , Feltracco Paolo , Simioni Paolo , Burra Patrizia , Cillo Umberto 
Published: July 2023

Background and Aims:
HCC can increase the risk of nonneoplastic PVT in cirrhosis. However, the natural history of PVT and its prognostic role in HCC patients are unknown.

Approach and Results:
Consecutive HCC patients with cirrhosis undergoing laparoscopic ablation were retrospectively evaluated and followed up to 36 months. HCC and PVT characteristics and evolution were reviewed. PVT was categorized according to lumen occupancy (≤50%, >50% <100%, and = 100%) and extension to other veins. The evolution of thrombosis was considered at 1 year from diagnosis. Variables associated with the presence of PVT and evolution patterns were analyzed, as well as their impact on survival. In all, 750 patients were included, 88 of whom had PVT. On multivariate analysis, the occurrence of PVT at HCC diagnosis was associated with pretreatment total tumor volume (p < 0.001) and clinically significant portal hypertension (p = 0.005). During the follow-up, 46 de novo PVT occurred, 27/46 (58.7%) in the presence of a viable tumor. Among 115 PVT diagnosed in the presence of HCC, 83 had available radiological follow-up, and 22 were anticoagulated. The “complete/progressive” evolution pattern was associated with nonresponse to HCC treatment in non-anticoagulated patients. The presence of PVT was independently associated with lower overall survival, particularly when progressive or occlusive (p < 0.001). A higher competing risk of death emerged for “complete and progressive” PVT, both for HCC-related (p < 0.001) and non-HCC–related (p = 0.002) death.

Conclusions:
HCC represents an independent risk factor for the occurrence and progression of PVT in cirrhosis. Since progressive and occlusive PVT seems to be an independent factor associated with mortality, screening and prompt treatment of this complication should be considered.
Chemotherapy with or without selective internal radiation therapy for intrahepatic cholangiocarcinoma: Data from clinical trials
Authors: Edeline Julien , Bridgewater John , Campillo-Gimenez Boris , Neveu Estelle , Phelip Jean-Marc , Neuzillet Cindy , Boudjema Karim , Rolland Yan , Valle Juan W. , Garin Etienne , Malka David , Lamarca Angela 
Published: July 2023

Backgound and Aims:
In advanced, liver-only intrahepatic cholangiocarcinoma (iCCA), selective internal radiation therapy (SIRT) has been suggested as promising in nonrandomized studies. We aimed to compare data from patients with advanced, liver-only iCCA treated in the first line in clinical trials with either chemotherapy alone or the combination with SIRT.

Approach and Results:
We collected individual patients’ data from the ABC-01, ABC-02, ABC-03, BINGO, AMEBICA, and MISPHEC prospective trials. Data from patients with liver-only iCCA treated in chemotherapy-only arms of the first 5 trials were compared with data from patients treated with SIRT and chemotherapy in MISPHEC. Emulated target trial paradigm and Inverse Probability of Treatment Weighting (IPTW methods) using the propensity score were used to minimize biases. We compared 41 patients treated with the combination with 73 patients treated with chemotherapy alone, the main analysis being in 43 patients treated with cisplatin-gemcitabine or gemcitabine-oxaliplatin. After weighting, overall survival was significantly higher in patients treated with SIRT: median 21.7 months (95% CI: 14.1; not reached) versus 15.9 months(95% CI: 9.8; 18.9), HR = 0.59 (95% CI: 0.34; 0.99), p = 0.049. Progression-free survival was significantly improved: median 14.3 months (95% CI: 7.8; not reached) versus 8.4 months (95% CI: 5.9; 12.1), HR = 0.52 (95% CI: 0.31; 0.89), p < 0.001. Results were confirmed in most sensitivity analyses.

Conclusions:
This analysis derived from prospective clinical trials suggests that SIRT combined with chemotherapy might improve outcomes over chemotherapy alone in patients with advanced, liver-only iCCA. Randomized controlled evidence is needed to confirm these findings.
Itaconate inhibits CD103+ TRM cells and alleviates hepatobiliary injury in mouse models of primary sclerosing cholangitis
Authors: Li Yikang , Li Bo , Xiao Xiao , Qian Qiwei , Wang Rui , Lyu Zhuwan , Chen Ruiling , Cui Nana , Ou Yiyan , Pu Xiting , Miao Qi , Wang Qixia , Lian Min , Gershwin M. Eric , Tang Ruqi , Ma Xiong , You Zhengrui 
Published: July 2023

Background and Aims:
Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease characterized by the infiltration of intrahepatic tissue-resident memory CD8+ T cells (TRM). Itaconate has demonstrated therapeutic potential in modulating inflammation. An unmet need for PSC is the reduction of biliary inflammation, and we hypothesized that itaconate may directly modulate pathogenic TRM.

Approach and Results:
The numbers of intrahepatic CD103+ TRM were evaluated by immunofluorescence in PSC (n = 32), and the serum levels of itaconate in PSC (n = 64), primary biliary cholangitis (PBC) (n = 60), autoimmune hepatitis (AIH) (n = 49), and healthy controls (n = 109) were determined by LC-MS/MS. In addition, the frequencies and immunophenotypes of intrahepatic TRM using explants from PSC (n = 5) and healthy donors (n = 6) were quantitated by flow cytometry. The immunomodulatory properties of 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) on CD103+ TRM were studied in vitro. Finally, the therapeutic potential of itaconate was studied by the administration of 4-OI and deficiency of immune-responsive gene 1 (encodes the aconitate decarboxylase producing itaconate) in murine models of PSC. Intrahepatic CD103+ TRM was significantly expanded in PSC and was positively correlated with disease severity. Serum itaconate levels decreased in PSC. Importantly, 4-OI inhibited the induction and effector functions of CD103+ TRM in vitro. Mechanistically, 4-OI blocked DNA demethylation of RUNX3 in CD8+T cells. Moreover, 4-OI reduced intrahepatic CD103+ TRM and ameliorated liver injury in murine models of PSC.

Conclusions:
Itaconate exerted immunomodulatory activity on CD103+ TRM in both in vitro and murine PSC models. Our study suggests that targeting pathogenic CD103+ TRM with itaconate has therapeutic potential in PSC.
Novel Manifestation of Corneal Dystrophy After Keratorefractive Surgery
Authors: Yeh Tsai-Chu , Hsu Chih-Chien , Lu Yung-Hsiu , Chen Yun-Ru , Niu Dau-Ming , Lin Pei-Yu 
Published: July 2023

Purpose:
This study aimed to report cases of bilateral corneal Bowman layer deposits in 4 patients with a history of keratorefractive surgery. To our knowledge, this condition has not previously been reported and should be distinguished from granular corneal dystrophy type 2 and other corneal dystrophies.

Methods:
We reviewed all available medical records that were collected between January 2010 and December 2021 at a tertiary referral center and performed whole-exome sequencing to provide diagnostic information.

Results:
Four patients exhibited similar bilateral corneal deposits that were observed more than 10 years after keratorefractive surgery. The patients' ages ranged from 36 to 53 years; 3 of the 4 patients were female. Three patients received laser in situ keratomileusis surgery, and 1 received radial keratotomy. All 4 patients denied having a family history of ocular diseases and reported an uneventful postoperative course. On examination, the best-corrected visual acuity ranged from 6/10 to 6/6 in all 4 patients. Slit-lamp examination revealed bilateral superficial corneal deposits involving the central cornea, and anterior segment optical coherence tomography revealed hyperreflective deposits located in the Bowman layer. Such unique manifestations suggested corneal dystrophy; thus, whole-exome sequencing was performed on all 4 patients. Only 1 patient exhibited a missense mutation in TGFBI. We further analyzed common de novo mutations to explore possible candidate genes associated with this presentation.

Conclusions:
We report a rare entity of presumed corneal dystrophy with deposits located in the Bowman layer in 4 patients who had received keratorefractive surgery. Clarifying the underlying pathophysiology and genetic predisposition of this disease may aid in diagnosing and preventing potential complications after keratorefractive surgery.
Inadequate Lopinavir Concentrations With Modified 8-Hourly Lopinavir/Ritonavir 4:1 Dosing During Rifampicin-based Tuberculosis Treatment in Children Living With HIV
Authors: Chabala Chishala , Turkova Anna , Kapasa Monica , LeBeau Kristen , Tembo Chimuka H. , Zimba Kevin , Weisner Lubbe , Zyambo Khozya , Choo Louise , Chungu Chalilwe , Lungu Joyce , Mulenga Veronica , Crook Angela , Gibb Diana , McIlleron Helen ,   on behalf of the SHINE trial team
Published: July 2023

Background:
Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment.

Methods:
Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment.

Results:
Of 20 children enrolled; 15, 1–7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve0–24 55.32 mg/h/L [0.30–398.7 mg/h/L]; Cmax 3.04 mg/L [0.03–18.6 mg/L]; C8hr 0.90 mg/L [0.01–13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve24 121.63 mg/h/L [2.56–487.3 mg/h/L]; Cmax 9.45 mg/L [0.39–26.4 mg/L]; C12hr 3.03 mg/L [0.01–17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L.

Conclusions:
Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation.
Work-Life Balance and Mental Health Outcomes for Generation Z in Germany
Authors: Adedeji Adekunle , Langel Carlotta , Feick Amelie , Borges Greibaum Martha-Sofia , Rahimi Maryam , Hanft-Robert Saskia 
Published: July 2023

Objective
Mental health can be negatively affected if work and private life demands are not balanced. This study proposes exploring work-life balance (WLB) as a predictor of Generation Z's mental health outcomes.

Methods
A cross-sectional online study was conducted to collect data on mental health outcomes and WLB from a sample of Generation Z (N = 134). Three regression models were calculated to examine the predictive effect of WLB on stress, anxiety, and depressive symptoms.

Results
The results show a strong statistically significant association between all three mental health outcomes. The regression model suggests work-life balance as a predictor of stress (β =.−0.404 P = 0.001, R2 = 0.16) and anxiety (β = .−256 P = 0.001, R2 = 0.06).

Conclusion
WLB must be considered a significant factor in mental health problems among Generation Z.
Transcanal Endoscopic Management of Middle Ear Paragangliomas
Authors: Surmelioglu Ozgur , Bajin Munir Demir , Kaya Isa , Okuyucu Semsettin , Ozturk Kayhan , Orhan Kadir Serkan , Karlıdag Turgut , Ardıc Fazil Necdet , Ozdek Ali , Yorgancılar Ediz , Dagkiran Muhammed , Celik Mehmet 
Published: July 2023

Objective
To evaluate the clinical and audiological outcomes of transcanal endoscopic resection of middle ear paragangliomas.

Study Design
Retrospective multicenter study.

Setting
Tertiary referral center and private otology clinic.

Patients
Patients who underwent transcanal endoscopic surgery between January 2015 and September 2020.

Intervention(s)
Transcanal endocope-assisted resection of middle ear paragangliomas.

Main Outcome Measure(s)
Demographic data.

Results
Twenty-three patients (2 men, 21 women) with a mean (standard deviation [SD]) age of 50.5 (11.8) years and stage 1 or 2 disease were included in the study. The mean follow-up time was 2.7 years (range, 1–5 yr). Preoperatively, the mean (SD) air-conduction threshold was 33.8 (17.9) dB, and the mean (SD) air-bone gap was 13.1 (13.9) dB. Postoperatively, the mean (SD) air-conduction threshold was 25.7 (10.2) dB, the mean (SD) air-bone gap was 6.3 (6.1) dB. The mean (SD) hospital stay was 27.7 (9.9) hours. No tumor regrowth was detected on magnetic resonance imaging during postoperative follow-up.

Conclusions
Endoscopic transcanal tumor resection is effective and feasible in the treatment of stage 1 and 2 tumors and is associated with short operative time, low risk of perioperative and postoperative complications, and rapid discharge.
Round-Window Vibroplasty: Systematic Review and Meta-Analysis of Audiological Effectiveness With Different Round-Window Coupling Techniques
Authors: Hundertpfund Julia , Dejaco Thomas , Meyer Jens Eduard , Óvári Attila 
Published: July 2023

Objective
Active middle ear implants can be directly coupled to the round-window (RW) membrane via RW Vibroplasty. The objectives of this systematic review were to summarize data on different RW coupling techniques and to investigate their effect on audiological and safety outcomes using meta-analyses.

Databases reviewed
PubMed (MEDLINE), Cochrane Library, and Embase (DIMDI).

Methods
All publications reporting on audiological outcomes in human patients after RW Vibroplasty were included. Two independent reviewers carried out screening and data extraction. Meta-analyses and meta-regression were used to evaluate the potential effects of surgical and demographic parameters on primary audiological outcomes. Adverse events were extracted and tabulated for qualitative analysis.

Results
Fourteen different combinations of surgical coupling parameters were identified in 61 included publications. Overall, data from 23 publications could be used for meta-analyses. Significantly better aided sound-field thresholds were reported for RW Vibroplasty performed without a dedicated coupler and using fascia as interponate, compared with RW Vibroplasty with an RW coupler or without an interponate. These effects were not found in other outcomes (i.e., functional gain, word recognition score). Reporting of adverse events was relatively heterogeneous, with 32 explicit mentions of revision surgery after the loss of coupling efficacy.

Conclusion
There are numerous publications investigating the effectiveness of coupling active middle ear implants to the RW membrane. However, studies are typically undersampled and of low evidence level. Using meta-analyses, weighted means, and qualitative analyses enabled a summary of the existing literature on audiological and safety outcomes after RW Vibroplasty. Individual selection of the most appropriate coupling modality with standardized intraoperative measurement and careful patient follow-up may be considered key factors for achieving effective RW coupling.
Predictors of Career Placement Among American Neurotology Society Fellowship Graduates
Authors: Choe Erica , Hakimi Amir A. , Hoa Michael 
Published: July 2023

Abstract and Objective
To identify predictors of practice type and location after neurotology fellowship based on demographics and educational history.

Study Design
Cross-sectional analysis.

Setting
Conference programs from the American Neurotology Society Spring Meeting from 2016 to 2022.

Main Outcome Measure
Percentage of neurotologists who pursued academic careers.

Results
A total of 114 neurotology fellows were identified. Of the 98 individuals included in final analysis, 64 (65%) pursued academic careers. Fellows most likely to enter academic practice trained at a residency program ranked in the top 50% based on Doximity residency rankings by reputation (74 versus 45%, p < 0.01) or graduated from a residency program with a neurotology fellowship (82 versus 56%, p < 0.01). Graduates from fellowship programs in the Northeast were most likely to enter academic careers (83%). Fifty percent of neurotologists practiced in the same region as their residency training, and 48% practiced the same region as their fellowship. The region with the highest number of practicing neurotology graduates was the South (47%).

Conclusion
Residency program ranking and residency institutions with neurotology fellowships were the leading predictors of academic career placement in the field of neurotology. Many neurotologists tend to stay in a similar geographical location to where they underwent medical training.
Speed of Information Processing and Verbal Working Memory in Children and Adolescents With Cochlear Implants
Authors: Herran Reid M. , Montgomery Caitlin J. , Henning Shirley C. , Herbert Carolyn J. , Ditmars Allison M. , Yates Catherine J. , Pisoni David B. , Kronenberger William G. 
Published: July 2023

Background
Verbal working memory delays are found in many deaf children with cochlear implants compared with normal-hearing peers, but the factors contributing to these delays are not well understood. This study investigated differences between cochlear implant users and normal-hearing peers in memory scanning speed during a challenging verbal working memory task. To better understand variability in verbal working memory capacity within each sample, associations between memory scanning speed, speech recognition, and language were also investigated.

Methods
Twenty-five prelingually deaf, early implanted children (age, 8–17 yr) with cochlear implants and 25 normal-hearing peers completed the Wechsler Intelligence Scale for Children, Fifth Edition, Letter-Number Sequencing (LNS) working memory task. Timing measures were made for response latency and average pause duration between letters/numbers recalled during the task. Participants also completed measures of speech recognition, vocabulary, and language comprehension.

Results
Children with cochlear implants had longer pause durations than normal-hearing peers during three-span LNS sequences, but the groups did not differ in response latencies or in pause durations during two-span LNS sequences. In the sample of cochlear implant users, poorer speech recognition was correlated with longer pause durations during two-span sequences, whereas poorer vocabulary and weaker language comprehension were correlated with longer response latencies during two-span sequences. Response latencies and pause durations were unrelated to language in the normal-hearing sample.

Conclusion
Children with cochlear implants have slower verbal working memory scanning speed than children with normal hearing. More robust phonological-lexical representations of language in memory may facilitate faster memory scanning speed and better working memory in cochlear implant users.