bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial
Authors: Jansen Simone C. , van Lemmen Maarten , Olofsen Erik , Moss Laurence , Pergolizzi Joseph V. , Miller Thomas , Colucci Robert D. , van Velzen Monique , Kremer Philip , Dahan Albert , van der Schrier Rutger , Niesters Marieke 
Published: January 2024

Background
The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. They hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response.

Methods
In this randomized, double-blind crossover trial, 14 male and female healthy volunteers were randomized to receive placebo and low- and high-dose ENA-001 on three separate occasions. On each occasion, isohypercapnic hypoxic ventilatory responses were measured during a fixed sequence of placebo, followed by low- and high-dose propofol infusion. The authors conducted a population pharmacokinetic/pharmacodynamic analysis that included oxygen and carbon dioxide kinetics.

Results
Twelve subjects completed the three sessions; no serious adverse events occurred. The propofol concentrations were 0.6 and 2.0 µg/ml at low and high dose, respectively. The ENA-001 concentrations were 0.6 and 1.0 µg/ml at low and high dose, respectively. The propofol concentration that reduced the hypoxic ventilatory response by 50% was 1.47 ± 0.20 µg/ml. The steady state ENA-001 concentration to increase the depressed ventilatory response by 50% was 0.51 ± 0.04 µg/ml. A concentration of 1 µg/ml ENA-001 was required for full reversal of the propofol effect at the propofol concentration that reduced the hypoxic ventilatory response by 50%.

Conclusions
In this pilot study, the authors demonstrated that ENA-001 restored the hypoxic ventilatory response impaired by propofol. This finding is not only of clinical importance but also provides mechanistic insights into the peripheral stimulation of breathing with ENA-001 overcoming central depression by propofol.

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Pruritus Anesis in Dystrophic Epidermolysis Bullosa Pruriginosa with Dupilumab
Authors: Yang Dan-Yang , Jing Wen-Wen , Liu Xin , Li Li , Lu Tao , Li Xiao-Li 
Published: January 2024

ABSTRACT
Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of dystrophic epidermolysis bullosa, and traditional treatments have limited efficacy. Dupilumab has demonstrated remarkable efficacy in relieving pruritus. In this case study, after traditional treatment failed, providers recommended the patient begin dupilumab to treat his pruritus. The patient was administrated a loading dose of 600 mg of dupilumab and a dose of 300 mg every 2 weeks. The Dermatology Life Quality Index and Pruritic Numeric Rating Scale were used to assess the patient’s situation. After several months, the patient’s DEB-Pr was considered in remission. Dupilumab may be a better choice than immunosuppressants for the treatment of pruritus in patients with DEB-Pr.
Intramedullary Impaction of the Basicervical Component is Determinant of Fixation Failure in a Simple Two-Part Pertrochanteric Fracture
Authors: Hong Seok Ha , Yu Kang Hun , Han Seung Beom 
Published: January 2024

Objectives:
To evaluate initial fracture morphology influences on outcomes in simple two-part pertrochanteric fracture, with a focus on the basicervical component and its initial impaction.

Methods:

Design:
A retrospective cohort series

Setting:
Single Level I Trauma Center

Patients Selection Criteria:
Patients over 60 years of age with intertrochanteric fractures between 2011 and 2022 were retrospectively reviewed. Inclusion criteria comprised simple two-part pertrochanteric fractures (OTA/AO 31-A1.2) with a basicervical component who underwent cephalomedullary nailing and had a minimum follow-up of 6 months. Patients were divided whether the basicervical component was impacted into the medullary canal (intramedullary impaction (II) group) or displaced beyond the medullary canal (extramedullary (E) group). Exclusion criteria encompassed pathologic fractures, nondisplaced fractures, and basicervical neck fractures (OTA/AO 31-B3).

Outcome Measurements and Comparisons:
Reduction status was assessed as unacceptable if the head and neck (proximal) fragment was positioned intramedullary with respect to the distal fragment in either the AP or cross-lateral X-ray, and acceptable otherwise. Also, the degree of impaction on X-ray and CT scans (coronal, sagittal, axial) at injury were analyzed as a risk factor for failure. Revision rates and lag screw sliding over 15mm were compared between the II and E groups.

Results:
115 patients (95 female, average age 80 years) were included. The II group (n=58) compared to E group (n=57) showed more acceptable postoperative reductions (57% vs 81%, p=0.001), but significantly higher fixation failure (16% vs. 3.5%, p=0.048) and fracture collapse (28% vs. 7%, p=0.01). Intramedullary impaction was identified as a significant independent predictor for failure (OR 5.64, 95% CI 2.14-16.9, p<0.001) with more than 19.5mm impaction in sagittal CT scan as the threshold linked to increased failure risk.

Conclusion:
The current study highlights the significance of specific intertrochanteric fracture patterns, particularly intramedullary impaction of a basicervical component and impaction severity (≥19.5mm), as drivers of fixation failure.
Survival for Nonshockable Cardiac Arrests Treated With Noninvasive Circulatory Adjuncts and Head/Thorax Elevation*
Authors: Bachista Kerry M. , Moore Johanna C. , Labarère José , Crowe Remle P. , Emanuelson Lauren D. , Lick Charles J. , Debaty Guillaume P. , Holley Joseph E. , Quinn Ryan P. , Scheppke Kenneth A. , Pepe Paul E. 
Published: January 2024

OBJECTIVES:
Cardiac arrests remain a leading cause of death worldwide. Most patients have nonshockable electrocardiographic presentations (asystole/pulseless electrical activity). Despite well-performed basic and advanced cardiopulmonary resuscitation (CPR) interventions, patients with these presentations have always faced unlikely chances of survival. The primary objective was to determine if, in addition to conventional CPR (C-CPR), expeditious application of noninvasive circulation-enhancing adjuncts, and then gradual elevation of head and thorax, would be associated with higher likelihoods of survival following out-of-hospital cardiac arrest (OHCA) with nonshockable presentations.

DESIGN:
Using a prospective observational study design (ClinicalTrials.gov NCT05588024), patient data from the national registry of emergency medical services (EMS) agencies deploying the CPR-enhancing adjuncts and automated head/thorax-up positioning (AHUP-CPR) were compared with counterpart reference control patient data derived from the two National Institutes of Health clinical trials that closely monitored quality CPR performance. Beyond unadjusted comparisons, propensity score matching and matching of time to EMS-initiated CPR (TCPR) were used to assemble cohorts with corresponding best-fit distributions of the well-established characteristics associated with OHCA outcomes.

SETTING:
North American 9-1-1 EMS agencies.

PATIENTS:
Adult nontraumatic OHCA patients receiving 9-1-1 responses.

INTERVENTIONS:
In addition to C-CPR, study patients received the CPR adjuncts and AHUP (all U.S. Food and Drug Administration-cleared).

MEASUREMENTS AND MAIN RESULTS:
The median TCPR for both AHUP-CPR and C-CPR groups was 8 minutes. Median time to AHUP initiation was 11 minutes. Combining all patients irrespective of lengthier response intervals, the collective unadjusted likelihood of AHUP-CPR group survival to hospital discharge was 7.4% (28/380) vs. 3.1% (58/1,852) for C-CPR (odds ratio [OR], 2.46 [95% CI, 1.55–3.92]) and, after propensity score matching, 7.6% (27/353) vs. 2.8% (10/353) (OR, 2.84 [95% CI, 1.35–5.96]). Faster AHUP-CPR application markedly amplified odds of survival and neurologically favorable survival.

CONCLUSIONS:
These findings indicate that, compared with C-CPR, there are strong associations between rapid AHUP-CPR treatment and greater likelihood of patient survival, as well as survival with good neurological function, in cases of nonshockable OHCA.
Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study*
Authors: Palmowski Lars , von Busch Alexander , Unterberg Matthias , Bergmann Lars , Schmitz Stefanie , Schlüter Andreas , Peters Jürgen , Adamzik Michael , Rahmel Tim 
Published: January 2024

OBJECTIVE:
Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term continuation. We tested the hypotheses that nonindicated PPI therapy continued beyond hospital discharge is associated with increased morbidity, rehospitalization rate, and mortality.

DESIGN:
Nationwide retrospective cohort study considering critically ill patients treated on German ICUs between January, 2017, and December, 2018 with a 2-year follow-up.

SETTING:
A total of 591,207 patient datasets of a German healthcare insurer were screened.

PATIENTS:
We identified 11,576 ICU patients who received PPI therapy for the first time during their index ICU stay without having an indication for its continuation.

INTERVENTIONS:
The cohort was stratified into two groups: 1) patients without further PPI therapy and 2) patients with continuation of PPI therapy beyond 8 weeks after hospital discharge.

MEASUREMENTS AND MAIN RESULTS:
Frequency of predescribed adverse events associated with PPI therapy, 1-year rehospitalization rate, and 2-year mortality were determined. The proportion of patients with continued PPI therapy without an objectifiable indication was 41.7% (4,825 of 11,576 patients). These patients had a 27% greater risk of pneumonia (odds ratio [OR] 1.27; 95% CI, 1.15–1.39; p < 0.001) and a 17% greater risk of cardiovascular events (OR 1.17; 95% CI, 1.08–1.26; p < 0.001). Continued PPI therapy was associated with a 34% greater risk of rehospitalization (OR 1.34; 95% CI, 1.23–1.47) and a nearly 20% greater 2-year mortality risk (hazard ratio 1.17; 95% CI, 1.08–1.27; p = 0.006).

CONCLUSIONS:
These data demonstrate that an unnecessary continuation of PPI therapy after hospital discharge may significantly impact morbidity and mortality. To avoid potentially harmful overuse of a PPIs, intensivists should ensure timely cessation of a temporarily indicated PPI therapy.
Aryl hydrocarbon receptor: Linking environment to aging process in elderly patients with asthma
Authors: Yang Tianrui , Wan Rongjun , Tu Wei , Avvaru Sai Nithin , Gao Peisong 
Published: January 2024

Abstract
Aging is a significant risk factor for various diseases, including asthma, and it often leads to poorer clinical outcomes, particularly in elderly individuals. It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage, resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases. The effects of aging affect not only the elderly but also those of younger ages, posing significant challenges to global healthcare. Thus, understanding the molecular mechanisms associated with aging in different diseases is essential. One intriguing factor is the aryl hydrocarbon receptor (AhR), which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process. Here, we review the literature on several major hallmarks of aging, including mitochondrial dysfunction, cellular senescence, autophagy, mitophagy, epigenetic alterations, and microbiome disturbances. Moreover, we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures, particularly in relation to the immune system. Furthermore, we explore how aging hallmarks affect clinical characteristics, inflammatory features, exacerbations, and the treatment of asthma. It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.
Cheek Reconstruction with a Nasolabial External-Rotation Flap
Authors: Ishii Nobuaki , Akimoto Masataka , Ogawa Rei 
Published: January 2024

Summary:
It remains difficult to reconstruct large preauricular defects in a single step with good cosmetic outcomes. We describe here the nasolabial external-rotation (NER) flap, which was combined with a cervical-rotation flap to reconstruct a large skin defect on the preauricular area that included the malar prominence. The patient in case 1 was a 91-year-old man who had a large defect on his right cheek after excision of a squamous cell carcinoma. Three weeks after excision, the 6.5 × 5.5 cm defect was covered with a 5 × 3 cm NER flap, which had a cephalad base and was rotated so its caudal tip covered the malar prominence. The resulting nasolabial defect and the remaining defect occupied the entire buccomandibular area, which was then covered with a 13 × 10 cm cervical-rotation flap. Revision surgery has not been needed for 8.5 months and the cosmetic outcomes are good. The patient in case 2 was a 90-year-old man who had a large defect on his right cheek after excision of a squamous cell carcinoma. Four weeks after excision, the 4.7 × 4 cm defect was covered with an 8 × 3 cm NER flap. The buccomandibular defect was covered with a 9.5 × 5 cm cervical-rotation flap. The flaps survived completely. The NER flap is unique because the flap is moved from the midface to the lateral face. It can reconstruct the malar prominence with thick skin tissue, and it is particularly suitable for older patients. Combining it with a cervical-rotation flap allows for natural subunit reconstruction in a relatively minimally invasive manner with good aesthetic outcomes.
TMR for Peripheral Sensory Nerve Neuroma around the Wrist Utilizing the Distal Anterior Interosseous Nerve
Authors: Muneer Mohammed 
Published: January 2024

Summary:
Injury to the peripheral sensory nerves of the hand and wrist is common and can lead to debilitating neuromas and significantly impair patients’ quality of life. Target-muscle reinnervation (TMR) is a novel method for treating neuromas that can result in significant clinical improvement. However, TMR for the peripheral sensory nerves in the hand and wrist is restricted by the limited options for motor branches. The adaptability of the anterior interosseous nerve (AIN) as a target for TMR treating peripheral sensory neuroma has not been thoroughly investigated or implemented therapeutically. This study aimed to evaluate the use of AIN as a viable recipient of TMR for treating peripheral sensory neuromas around the wrist. In this retrospective study, eight patients were included over 18 months from June 2021 to January 2023 at Hamad Medical Corporation. The average follow-up time after TMR was 13 months. The peripheral sensory nerves involved were the radial sensory nerve in five cases, the palmar cutaneous branch of the median nerve in one case, and the median nerve in one case. The preoperative average VAS pain score was 7 of 10 compared with the postoperative pain score of 2 of 10. In conclusion, the AIN can be used as a first-choice motor target for all peripheral sensory neuromas around the wrist for the following reasons: first, it can be reached by the peripheral sensory nerves around the wrist; second, the pronator quadratus muscle is expandable; and third, the AIN can be taken with a long proximal tail for flexible coaptation with the peripheral sensory nerves.
Primary Periocular Orofacial Granulomatosis: Case Series and Systematic Review
Authors: Plemel David J. A. , Weis Ezekiel , Punja Karim G. , Ashenhurst Michael E. , Mai Derek D. , Kulaga Andrzej 
Published: January 2024

Purpose:
There is no known optimal treatment for primary periocular orofacial granulomatosis (PPOFG), a disorder that results in periocular edema. This case series and systematic review identifies management strategies and their reported improvement.

Methods:
Systematic review and case series. PubMed and MEDLINE databases were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to identify published cases of PPOFG. Cases were included when edema involved the periocular tissues and when a biopsy was interpreted to be PPOFG. Cases were excluded when edema did not involve the periocular tissues or when the edema was secondary to another process. The electronic medical records of the pathology department were studied to identify cases that were in keeping with PPOFG. The clinical charts were examined to confirm the diagnosis and provide a local case series.

Results:
There are 38 published cases of PPOFG. An additional 9 cases were identified locally. These cases were combined and analyzed. Most PPOFG has eyelid swelling in isolation, without other facial swelling (36/47; 76.6%). It is most commonly a bilateral disease (30/47; 63.8%). Fissured tongue and facial nerve palsy occur, just as they do in other cases of orofacial granulomatosis. Treatment with surgical debulking or intralesional steroids resulted in high rates of symptomatic improvement of eyelid swelling, but recurrences were common.

Conclusions:
In light of no curative or highly successful treatment currently available, intralesional steroids and/or surgical debulking are therapies in the treatment of eyelid swelling associated with PPOFG that demonstrate reasonable short- and medium-term results. There is no established therapy that can offer disease remission or long-term symptom improvement.
Orbital Trapdoor Fracture With Extraocular Muscle Entrapment in Adults: A Case Series
Authors: Miyazaki Hidetaka , Someda Steffani Krista , Yokoyama Tatsuro , Vaidya Aric , Kakizaki Hirohiko , Takahashi Yasuhiro 
Published: January 2024

Purpose:
To report adult patients with an orbital trapdoor fracture with extraocular muscle entrapment.

Methods:
We retrospectively reviewed 566 adult patients (>18 years) with a pure orbital fracture who were referred to us from January 2016 to May 2023. The following data were collected: age, sex, affected side, causes of injury, concomitant ocular injury and nasal bone fracture, presence or absence of oculocardiac reflex and infraorbital nerve hypesthesia, period from injury to surgery, follow-up period, and pre- and postoperative limitation of extraocular muscle motility and fields of a binocular single vision.

Results:
We found 5 patients (0.9%) with an orbital trapdoor fracture with extraocular muscle entrapment (age range, 19–47 years; all males; 2 right and 3 left). Causes of injury included performing a bench press, fall, assault, boxing, and bicycle accident. Entrapment of the inferior and medial recti muscles was seen in 2 and 3 patients, respectively. None of the patients had any sign of oculocardiac reflex. After surgical reduction, the field of binocular single vision became normal in 3 patients and was incompletely recovered in 2 patients, in whom consultation with us was delayed.

Conclusion:
Adults with extraocular muscle entrapment may not present with an oculocardiac reflex. Urgent release of an entrapped muscle is, however, still recommended to avoid permanent limitation of extraocular muscle motility.
Quantitative Assessment of Subjective Symptoms and Corneal Sensitivity in Chronic Orbital Pain Patients
Authors: Lee Grace , Kardon Randy H. , Nellis Julie K. , Pham Chau M. , Sales Christopher S. , Carter Keith D. , Shriver Erin M. 
Published: January 2024

Purpose:
To objectively evaluate the subjective symptoms and characteristics of chronic orbital pain as well as to quantify sensitization of peripheral trigeminal nerves.

Methods:
In this prospective cohort study, patients who previously showed a response to peripheral trigeminal nerve blocks for unilateral, idiopathic chronic orbital pain and healthy subjects completed validated questionnaires assessing headaches, neuropathic signs and symptoms, photophobia, and pain qualities. Corneal sensitivity was measured in both eyes for all subjects with a Cochet-Bonnet aesthesiometer. For pain patients, the full assessment protocol was repeated 2–4 weeks after the study injection, and corneal sensitivity was also measured 30 minutes postinjection. Outcomes assessed were headache, neuropathic pain, and photophobia scores; pain qualities; and corneal sensitivity.

Results:
Six female chronic orbital pain patients (mean age 48.2 years) and 11 female controls (mean age 47.5) were included. The mean headache, neuropathic pain, and photophobia questionnaire scores were significantly higher for pain patients than for controls (p < 0.001). On sensory testing, 5 pain patients (83.3%) endorsed allodynia, and all 6 (100%) had hyperalgesia in the ipsilateral frontal nerve dermatome. No controls had allodynia or hyperalgesia. Corneal sensitivity was similar between eyes in pain patients and between groups. Questionnaire scores and corneal sensitivity did not change significantly after the injection.

Conclusions:
Chronic orbital pain patients have a measurable reduction in quality of life due to headaches and photophobia. The supraorbital and supratrochlear nerves are sensitized, resulting in cutaneous hypersensitivity in the corresponding dermatome, but corneal nerves have normal sensitivity.