Preoperative Degenerative Changes at the Tibial Sesamoid-Metatarsal Joint in Hallux Valgus: Association With Postoperative Patient-Reported Outcomes After Modified Lapidus Procedure.

Background: Degenerative changes at the sesamoid-metatarsal joints (SMJs) may be a source of pain following hallux valgus surgery. The aims of this study were to describe degenerative changes at the SMJs on weightbearing computed tomography (WBCT) scans and, secondarily, investigate their association with 1-year patient-reported outcome scores following a modified Lapidus procedure for hallux valgus. We hypothesized that reduced joint space in the SMJs would correlate with worse patient-reported outcomes. Methods: Fifty-seven hallux valgus patients who underwent a modified Lapidus procedure had preoperative and minimum 5-month postoperative WBCT scans, and preoperative and at least 1-year postoperative PROMIS physical function (PF), pain interference, and pain intensity scores were included. Degenerative changes at the SMJs were measured using distance mapping between the sesamoids and first metatarsal head on preoperative and postoperative WBCT scans. The minimum and average distances between the first metatarsal head and tibial sesamoid (tibial-SMJ) for each patient preoperatively and postoperatively were measured. Sesamoid station was measured on WBCT scans using a 0 to 3 grading system. Linear regression was used to investigate the correlations between minimum preoperative and postoperative tibial-SMJ distances and 1-year postoperative PROMIS scores. Results: The median minimum and average tibial-SMJ distances increased from 0.82 mm (interquartile range [IQR] 0.40-1.03 mm) and 1.62 mm (IQR 1.37-1.75 mm) preoperative to 1.09 mm (IQR 0.96-1.23 mm) and 1.73 mm (IQR 1.60-1.91 mm) postoperative (P < .001 and P < .001), respectively. In a subset of patients with complete sesamoid reduction, we found an association between preoperative minimum tibial-SMJ distance and 1-year postoperative PROMIS PF scores (coefficient 7.2, P = .02). Conclusion: Following the modified Lapidus procedure, there was a statistically significant increase in the tibial-SMJ distance. Additionally, in patients with reduced sesamoids postoperatively, reduced preoperative tibial-SMJ distance correlated with worse PROMIS PF scores. Level of Evidence: Level IV, case series.

Defining the patient acceptable symptom state using PROMIS following reconstruction of the progressive collapsing foot deformity.

BACKGROUND: The patient acceptable symptom state (PASS) represents the threshold beyond which patients are satisfied with their outcome. This study aimed to define PASS thresholds for progressive collapsing foot deformity (PCFD) reconstruction using Patient-Reported Outcomes Measurement Information System (PROMIS) scores and anchor question responses. METHODS: This retrospective study consisted of 109 patients who underwent flexible PCFD reconstruction, had preoperative and 2-year postoperative PROMIS scores, and 2-year postoperative anchor question responses. ROC curve analyses were performed to quantify PASS thresholds. RESULTS: PASS thresholds for the PROMIS Physical Function (PF) and Pain Interference (PI) domains were found to be lower and higher, respectively, than population norms. Furthermore, patients with higher preoperative PROMIS PF scores or lower preoperative PROMIS PI scores had a significantly higher likelihood of achieving the PASS thresholds. CONCLUSION: In addition to guiding future outcomes research, these results may help surgeons optimize treatment for PCFD and better manage patient expectations. LEVEL OF EVIDENCE: III, retrospective cohort study.

A Taxonomically-verified and Vouchered Checklist of the Vascular Plants of the Republic of Guinea.

The Checklist of the Vascular Plants of the Republic of Guinea (CVPRG) is a specimen-based, expert-validated knowledge product, which provides a concise synthesis and overview of current knowledge on 3901 vascular plant species documented from Guinea (Conakry), West Africa, including their accepted names and synonyms, as well as their distribution and status within Guinea (indigenous or introduced, endemic or not). The CVPRG is generated automatically from the Guinea Collections Database and the Guinea Names Backbone Database, both developed and maintained at the Royal Botanic Gardens, Kew, in collaboration with the staff of the National Herbarium of Guinea. A total of 3505 indigenous vascular plant species are reported of which 3328 are flowering plants (angiosperms); this represents a 26% increase in known indigenous angiosperms since the last floristic overview. Intended as a reference for scientists documenting the diversity and distribution of the Guinea flora, the CVPRG will also inform those seeking to safeguard the rich plant diversity of Guinea and the societal, ecological and economic benefits accruing from these biological resources.

Enhanced recovery after surgery (ERAS®) society guidelines for gynecologic oncology: Addressing implementation challenges - 2023 update.

BACKGROUND: Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges. METHODS: Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018-2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly. CONCLUSIONS: The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.

Treatment Time and In-Hospital Mortality Among Patients With ST-Segment Elevation Myocardial Infarction, 2018-2021.

Importance: Recognizing the association between timely treatment and less myocardial injury for patients with ST-segment elevation myocardial infarction (STEMI), US national guidelines recommend specific treatment-time goals. Objective: To describe these process measures and outcomes for a recent cohort of patients. Design, Setting, and Participants: Cross-sectional study of a diagnosis-based registry between the second quarter of 2018 and the third quarter of 2021 for 114 871 patients with STEMI treated at 648 hospitals in the Get With The Guidelines-Coronary Artery Disease registry. Exposures: STEMI or STEMI equivalent. Main Outcomes and Measures: Treatment times, in-hospital mortality, and adherence to system goals (75% treated ≤90 minutes of first medical contact if the first hospital is percutaneous coronary intervention [PCI]-capable and ≤120 minutes if patients require transfer to a PCI-capable hospital). Results: In the study population, median age was 63 (IQR, 54-72) years, 71% were men, and 29% were women. Median time from symptom onset to PCI was 148 minutes (IQR, 111-226) for patients presenting to PCI-capable hospitals by emergency medical service, 195 minutes (IQR, 127-349) for patients walking in, and 240 minutes (IQR, 166-402) for patients transferred from another hospital. Adjusted in-hospital mortality was lower for those treated within target times vs beyond time goals for patients transported via emergency medical services (first medical contact to laboratory activation ≤20 minutes [in-hospital mortality, 3.6 vs 9.2] adjusted OR, 0.54 [95% CI, 0.48-0.60], and first medical contact to device ≤90 minutes [in-hospital mortality, 3.3 vs 12.1] adjusted OR, 0.40 [95% CI, 0.36-0.44]), walk-in patients (hospital arrival to device ≤90 minutes [in-hospital mortality, 1.8 vs 4.7] adjusted OR, 0.47 [95% CI, 0.40-0.55]), and transferred patients (door-in to door-out time <30 minutes [in-hospital mortality, 2.9 vs 6.4] adjusted OR, 0.51 [95% CI, 0.32-0.78], and first hospital arrival to device ≤120 minutes [in-hospital mortality, 4.3 vs 14.2] adjusted OR, 0.44 [95% CI, 0.26-0.71]). Regardless of mode of presentation, system goals were not met in most quarters, with the most delayed system performance among patients requiring interhospital transfer (17% treated ≤120 minutes). Conclusions and Relevance: This study of patients with STEMI included in a US national registry provides information on changes in process and outcomes between 2018 and 2021.

Systems of Care for ST-Segment-Elevation Myocardial Infarction: A Policy Statement From the American Heart Association.

The introduction of Mission: Lifeline significantly increased timely access to percutaneous coronary intervention for patients with ST-segment-elevation myocardial infarction (STEMI). In the years since, morbidity and mortality rates have declined, and research has led to significant developments that have broadened our concept of the STEMI system of care. However, significant barriers and opportunities remain. From community education to 9-1-1 activation and emergency medical services triage and from emergency department and interfacility transfer protocols to postacute care, each critical juncture presents unique challenges for the optimal care of patients with STEMI. This policy statement sets forth recommendations for how the ideal STEMI system of care should be designed and implemented to ensure that patients with STEMI receive the best evidence-based care at each stage in their illness.

Leptin receptor expression in the dorsomedial hypothalamus stimulates breathing during NREM sleep in db/db mice.

STUDY OBJECTIVES: Obesity leads to obstructive sleep apnea (OSA), which is recurrent upper airway obstruction during sleep, and obesity hypoventilation syndrome (OHS), hypoventilation during sleep resulting in daytime hypercapnia. Impaired leptin signaling in the brain was implicated in both conditions, but mechanisms are unknown. We have previously shown that leptin stimulates breathing and treats OSA and OHS in leptin-deficient ob/ob mice and leptin-resistant diet-induced obese mice and that leptin's respiratory effects may occur in the dorsomedial hypothalamus (DMH). We hypothesized that leptin receptor LepRb-deficient db/db mice have obesity hypoventilation and that restoration of leptin signaling in the DMH will increase ventilation during sleep in these animals. METHODS: We measured arterial blood gas in unanesthetized awake db/db mice. We subsequently infected these animals with Ad-LepRb or control Ad-mCherry virus into the DMH and measured ventilation during sleep as well as CO2 production after intracerebroventricular (ICV) infusions of phosphate-buffered saline or leptin. RESULTS: Awake db/db mice had elevated CO2 levels in the arterial blood. Ad-LepRb infection resulted in LepRb expression in the DMH neurons in a similar fashion to wildtype mice. In LepRb-DMH db/db mice, ICV leptin shortened REM sleep and increased inspiratory flow, tidal volume, and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2 production. Leptin had no effect on upper airway obstruction in these animals. CONCLUSION: Leptin stimulates breathing and treats obesity hypoventilation acting on LepRb-positive neurons in the DMH.

Designer Receptors Exclusively Activated by Designer Drugs Approach to Treatment of Sleep-disordered Breathing.

Rationale: Obstructive sleep apnea is recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep. The main goal of our study was to determine if designer receptors exclusively activated by designer drugs (DREADD) could be used to activate the genioglossus muscle as a potential novel treatment strategy for sleep apnea. We have previously shown that the prototypical DREADD ligand clozapine-N-oxide increased pharyngeal diameter in mice expressing DREADD in the hypoglossal nucleus. However, the need for direct brainstem viral injections and clozapine-N-oxide toxicity diminished translational potential of this approach, and breathing during sleep was not examined.Objectives: Here, we took advantage of our model of sleep-disordered breathing in diet-induced obese mice, retrograde properties of the adeno-associated virus serotype 9 (AAV9) viral vector, and the novel DREADD ligand J60.Methods: We administered AAV9-hSyn-hM3(Gq)-mCherry or control AAV9 into the genioglossus muscle of diet-induced obese mice and examined the effect of J60 on genioglossus activity, pharyngeal patency, and breathing during sleep.Measurements and Main Results: Compared with control, J60 increased genioglossus tonic activity by greater than sixfold and tongue uptake of 2-deoxy-2-[18F]fluoro-d-glucose by 1.5-fold. J60 increased pharyngeal patency and relieved upper airway obstruction during non-REM sleep.Conclusions: We conclude that following intralingual administration of AAV9-DREADD, J60 can activate the genioglossus muscle and improve pharyngeal patency and breathing during sleep.

Visual conditions affecting eye growth alter diurnal levels of vitreous DOPAC.

In chicks, the diurnal patterns of retinal dopamine synthesis and release are associated with refractive development. To assess the within-day patterns of dopamine release, we assayed vitreal levels of DOPAC (3,4-dihydroxyphenylacetic acid) using high performance liquid chromatography with electrochemical detection, at 4-h intervals over 24 h in eyes with experimental manipulations that change ocular growth rates. Chicks were reared under a 12 h light/12 h dark cycle; experiments began at 12 days of age. Output was assessed by modelling using the robust variance structure of Generalized Estimating Equations. Continuous spectacle lensdefocus or form deprivation: One group experienced non-restricted visual input to both eyes and served as untreated "normal" controls. Three experimental cohorts underwent monocular visual alterations known to alter eye growth and refraction: wearing a diffuser, a negative lens or a positive lens. After one full day of device-wear, chicks were euthanized at 4-h intervals over 24 h (8 birds per time/condition). Brief hyperopic defocus: Chicks wore negative lenses for only 2 daily hours either in the morning (starting at ZT 0; n = 16) or mid-day (starting at ZT 4; n = 8) for 3 days. Vitreal DOPAC was assayed. In chicks with bilateral non-restricted vision, or with continuous defocus or form-deprivation, there was a diurnal variation in vitreal DOPAC levels for all eyes (p < 0.001 for each). In normal controls, DOPAC was highest during the daytime, lowest at night, and equivalent for both eyes. In experimental groups, regardless of whether experiencing a growth stimulatory input (diffuser; negative lens) or growth inhibitory input (positive lens), DOPAC levels were reduced compared both to fellow eyes and to those of normal controls (p < 0.001 for each). These diurnal variations in vitreous DOPAC levels under different visual conditions indicate a complexity for dopaminergic mechanisms in refractive development that requires further study.

The characterization of cycad palm toxicosis and treatment effects in 130 dogs.

The purpose of this retrospective study is to characterize the clinical signs, laboratory values, treatment modalities and mortality outcomes related to cycad palm toxicosis in dogs and to identify medical interventions that potentially correlate with mortality. Dogs with confirmed cycad palm ingestion were identified by reviewing medical records from two private veterinary referral centres for key terms and phrases indicative of cycad palm toxicosis. Of 130 dogs included, 107 (82.3%) presented with clinical signs. A total of 2 (1.5%) died and 14 (10.8%) were euthanized. Diarrhea, lethargy and mortality were all associated with an elevated initial alanine transaminase (ALT) concentration. Overall mortality was 12.3%, with a significantly higher proportion of dogs with an ALT concentration <125 U/L surviving compared to dogs with an elevated ALT concentration. Treatment with activated charcoal reduced the odds of death among all dogs by 82% and was even more protective among dogs with an elevated initial ALT concentration. Among dogs that had an initial platelet count performed, the presence of thrombocytopenia (<200,000/µL) was a negative prognostic indicator and was associated with a significant increase in mortality. Given the high mortality rates reported for cycad palm toxicosis, it is imperative to identify early clinical indicators of mortality as well as treatments that reduce mortality.

Intranasal Leptin Prevents Opioid-induced Sleep-disordered Breathing in Obese Mice.

Respiratory depression is the main cause of morbidity and mortality associated with opioids. Obesity increases opioid-related mortality, which is mostly related to comorbid obstructive sleep apnea. Naloxone, a µ-opioid receptor blocker, is an effective antidote, but it reverses analgesia. Like humans with obesity, mice with diet-induced obesity hypoventilate during sleep and develop obstructive sleep apnea, which can be treated with intranasal leptin. We hypothesized that intranasal leptin reverses opioid-induced sleep-disordered breathing in obese mice without decreasing analgesia. To test this hypothesis, mice with diet-induced obesity were treated with morphine at 10 mg/kg subcutaneously and with leptin or placebo intranasally. Sleep and breathing were recorded by barometric plethysmography, and pain sensitivity was measured by the tail-flick test. Excitatory postsynaptic currents were recorded in vitro from hypoglossal motor neurons after the application of the µ-opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin and leptin. Morphine dramatically increased the frequency of apneas and greatly increased the severity of hypoventilation and obstructive sleep apnea. Leptin decreased the frequency of apneas, improved obstructive sleep apnea, and completely reversed hypoventilation, whereas morphine analgesia was enhanced. Our in vitro studies demonstrated that [D-Ala2, N-MePhe4, Gly-ol]-enkephalin reduced the frequency of excitatory postsynaptic currents in hypoglossal motoneurons and that application of leptin restored excitatory synaptic neurotransmission. Our findings suggest that intranasal leptin may prevent opioid respiratory depression during sleep in patients with obesity receiving opioids without reducing analgesia.

Cross-cutting view of current challenges in paediatric solid organ and haematopoietic stem cell transplantation in Europe: the European Reference Network TransplantChild.

The low prevalence of European paediatric transplanted patients and scarcity of resources and expertise led to the need for a multidisciplinary network able to improve the quality of life of paediatric patients and families requiring a solid organ or haematopoietic stem cell transplantation. The European Reference Network (ERN) TransplantChild is one of the 24 ERNs established in a European legal framework to improve the care of patients with rare diseases. ERN TransplantChild is the only ERN focused on both solid organ and haematopoietic stem cell paediatric transplantation, based on the understanding of paediatric transplantation as a complex and highly specialised process where specific complications appear regardless the organ involved, thus linking the skills and knowledge of different organ disciplines. Gathering European centres of expertise in paediatric transplantation will give access to a correct and timely diagnosis, share expertise and knowledge and collect a critical mass of patients and data that increases the speed and value of clinical research outcomes. Therefore, the ERN TransplantChild aims for a paediatric Pan-European, Pan-transplant approach.

Reduced disease severity following therapeutic treatment with angiotensin 1-7 in a mouse model of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by autoimmune and neurodegenerative pathologies for which there is no cure and no defined etiology. Although several, modestly effective, disease modifying drugs are available to treat MS, there are presently no treatments that offer neuroprotection and prevent clinical progression. Therapies are needed that control immune homeostasis, prevent disease progression, and stimulate regeneration in the CNS. Components of the renin-angiotensin-system (RAS) have recently been identified as chemical mediators in the CNS and in neurological disease. Here we show the beneficial effect of therapeutic treatment with the Mas receptor agonist and metabolite of the protective arm of RAS, angiotensin 1-7 (A(1-7)), in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Therapeutic treatment with A(1-7) caused a dose-dependent reduction both in clinical disease severity and progression, and was dependent on Mas receptor activation. Further analysis of the most optimal dose of A(1-7) treatment revealed that the reductions in clinical disease course were associated with decreased immune infiltration and demyelination, axonal loss and oxidative stress in the spinal cord. In addition A(1-7) treatment was also associated with increases in circulating alternatively activated monocytes/macrophages.

Paternal Age and Transgenerational Telomere Length Maintenance: A Simulation Model.

Telomere length (TL) in offspring is positively correlated with paternal age at the time of the offspring conception. The paternal-age-at-conception (PAC) effect on TL is puzzling, and its biological implication at the population level is unknown. Using a probabilistic model of transgenerational TL and population dynamics, we simulated the effect of PAC on TL in individuals over the course of 1,000 years. Findings suggest a key role for an isometric PAC midpoint (PACmp) in modulating TL across generations, such that offspring conceived by males younger than the isometric PACmp have comparatively short telomeres, while offspring conceived by males older than the isometric PACmp have comparatively long telomeres. We further show that when cancer incidence escalates, the average PAC drops below the isometric PACmp and transgenerational adaptation to cancer ensues through TL shortening. We propose that PAC serves to maintain an optimal TL across generations.

Anesthesia for Trauma Patients.

An improved understanding of the pathophysiology of combat trauma has evolved over the past decade and has helped guide the anesthetic care of the trauma patient requiring surgical intervention. Trauma anesthesia begins before patient arrival with warming of the operating room, preparation of anesthetic medications and routine anesthetic machine checks. Induction of anesthesia must account for potential hemodynamic instability and intubation must consider airway trauma. Maintenance of anesthesia is accomplished with anesthetic gas, intravenous infusions or a combination of both. Resuscitation must precede or be ongoing with the maintenance of anesthesia. Blood product transfusion, antibiotic administration, and use of pharmacologic adjuncts (e.g., tranexamic acid, calcium) all occur simultaneously. Ventilatory strategies to mitigate lung injury can be initiated in the operating room, and resuscitation must be effectively transitioned to the intensive care setting after the case. Good communication is vital to efficient patient movement along the continuum of care. The resuscitation that is undertaken before, during and after operative management must incorporate important changes in care of the trauma patient. This Clinical Practice Guideline hopes to provide a template for care of this patient population. It outlines a method of anesthesia that incorporates the induction and maintenance of anesthesia into an ongoing resuscitation during surgery for a trauma patient in extremis.

Differentiation of adipose derived stem cells to keratinocyte-like cells on an advanced collagen wound matrix.

Despite advances in tissue engineering and regenerative medicine, skin regeneration and cutaneous wound healing remains a significant medical challenge. A bioengineered skin that stimulates the body's natural regeneration capability is needed to address the current lack of treatment options. To this end, a biocompatible collagen wound matrix was developed using an electrochemical deposition fabrication process. The advanced collagen wound matrix has relatively high tensile strength compared to normal collagen matrix made by the heat gelation process and open porosity, and serves as an excellent platform for cellular growth and differentiation. Human adipose derived stem cells (hADSCs) were cultured on this collagen matrix and a co-culture system with primary keratinocytes and keratinocyte conditioned media was developed for differentiation of the hADSCs to keratinocyte-like cells. After fifteen days, hADSCs in co-culture began to exhibit a "cobblestone-like" morphology, indicating preliminary signs of differentiation to a keratinocyte-like cell. Based on morphological analysis at day 30, the co-culture with keratinocyte conditioned media system shows promising preliminary evidence of hADSC differentiation to a keratinocyte-like cell on an electrochemically aligned collagen wound matrix.

Trends and factors associated with radical cytoreductive surgery in the United States: A case for centralized care.

OBJECTIVES: To describe the US national trends and factors associated with cytoreductive surgical radicality in women with advanced ovarian cancer (OC). METHODS: An analysis of the National Inpatient Sample database was performed. All admissions from 1993 to 2011 for advanced OC cytoreductive surgery (CRS) were identified and categorized as simple pelvic (SP), extensive pelvic (EP), and extensive upper abdominal (EUA) surgery. Annual trends in CRS were analyzed. Associations between patient- and hospital-specific factors, with CRS radicality as well as perioperative complications were explored between 2007 and 2011. RESULTS: In total, 28,677 un-weighted admissions were analyzed. The rate of EP and EUA resections increased over time (8% to 18.1% and 1.3% to 5.4%, P<0.01, respectively). On multivariate analysis, patients were more likely to undergo EUA resections in the Northeast (OR 1.44) or West Coast (OR 1.47) at urban (OR 2.3), or large hospitals (OR 1.4), or if they had private insurance (OR 1.45). EUA surgeries were performed more frequently at high-volume ovarian cancer centers (OR 2.65); additionally, fewer complications were observed after EUA at high compared with low and medium volume hospitals (10.2%, 21.2%, and 21.7%, respectively; P=0.01). Specifically, patients treated at high volume hospitals experienced lower rates of hemorrhage, vascular/nerve injury, prolonged hospitalization, and non-routine discharge than at lower (P<0.05). CONCLUSIONS: The US rate of radical cytoreductive surgery for advanced ovarian cancer is increasing. At high-volume hospitals, patients receive more radical surgery with fewer complications, supporting further study of a centralized ovarian cancer care model.