bluuebunny/crossref_metadata_2025 huggingface dataset:
P81 Long-term efficacy of abrocitinib in adolescents and adults with moderate-to-severe atopic dermatitis: a post hoc analysis of JADE EXTEND
Authors: Paller Amy S , Cork Michael J , Flohr Carsten , Bangert Christine , Weidinger Stephan , Nesnas John , Farooqui Saleem A , Biswas Pinaki , Watkins Melissa , Koppensteiner Herwig
Published: June 2023

Differences exist in the manifestation and disease course of atopic dermatitis (AD) between adult and adolescent patients. Long-term efficacy of abrocitinib (an oral, once-daily Janus kinase 1-selective inhibitor) was examined in the phase III extension study JADE EXTEND (NCT03422822). This interim post hoc analysis assessed abrocitinib treatment efficacy up to 96 weeks in adolescents and adults with moderate-to-severe AD who enrolled in JADE EXTEND. Eligible adolescents (aged 12 to < 18 years) and adults (≥ 18 years) from the phase III trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), TEEN (NCT03796676) and DARE (NCT04345367) were enrolled in JADE EXTEND. Patients randomized to abrocitinib (200 mg or 100 mg) in the parent studies received blinded abrocitinib at the same dose in JADE EXTEND; those receiving placebo or dupilumab were randomized to either abrocitinib dose in JADE EXTEND. Patients from JADE DARE received abrocitinib 200 mg in JADE EXTEND. Analyses assessed the proportions of patients achieving an Investigator’s Global Assessment score of clear or almost clear (IGA 0/1); ≥ 75%, ≥ 90% and ≥ 100% improvement from baseline in Eczema Area and Severity Index (EASI-75, EASI-90 and EASI-100, respectively); ≥ 4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score (PP-NRS4; used with permission from Regeneron Pharmaceuticals and Sanofi); PP-NRS score of no or very little itch (PP-NRS 0/1); and ≥ 4-point improvement from baseline in the Patient Oriented Eczema Measure (POEM ≥ 4). The JADE EXTEND data cutoff date was 25 September 2021. This analysis included 357 adolescents and 1309 adults (excluding patients previously randomized to dupilumab). Age at parent study screening visit determined age categorization. Baseline disease severity was higher in adolescents than adults [IGA 4 (severe); 42.3% vs. 36.7%]. At week 96, responder proportions were comparable for adolescents and adults for EASI-75 (abrocitinib 200 mg: 84.4% vs. 85.7%; abrocitinib 100 mg: 81.3% vs. 76.1%), PP-NRS4 (200 mg: 69.4% vs. 69.3%; 100 mg: 60.3% vs. 59.8%) and POEM ≥ 4 (200 mg: 84.4% vs. 88.6%; 100 mg: 79.2% vs. 80.8%), and largely comparable for the stringent endpoints of EASI-90 (200 mg: 62.3% vs. 61.1%; 100 mg: 50.7% vs. 48.1%), EASI-100 (200 mg: 32.5% vs. 21.8%; 100 mg: 18.7% vs. 18.7%), IGA 0/1 (200 mg: 53.2% vs. 55.9%; 100 mg: 49.3% vs. 45.1%) and PP-NRS 0/1 (200 mg: 42.9% vs. 39.5%; 100 mg: 33.3% vs. 32.3%). Long-term efficacy of abrocitinib treatment up to 96 weeks was comparable for adolescents and adults with moderate-to-severe AD, including substantial proportions achieving stringent endpoints of EASI-90, EASI-100, IGA 0/1 or PP-NRS 0/1.

Funding sources: Pfizer Inc.
BG12 A case of severe gastrointestinal bleeding while on vismodegib therapy
Authors: Salih Hamisha , Ryan Sarah , Ascott Anna , DeGiovanni Claudia
Published: June 2023

We report the case of a 50-year-old woman, with a history of Gorlin syndrome on vismodegib therapy, who presented with two episodes of upper gastrointestinal bleeding (UGIB) in the absence of other risk factors. Gorlin syndrome is a rare disorder characterized by multiple basal cell carcinomas (BCCs) secondary to a mutation in PTCH1. Mutations in PTCH1 lead to dysregulation of the hedgehog signalling pathway and subsequent abnormal proliferation. Vismodegib is a systemic hedgehog inhibitor that has been shown to be effective in treating advanced BCCs and Gorlin syndrome. Our patient acquired multiple BCCs which excision, photodynamic therapy and topical chemotherapy agents failed to control. Therefore, a decision to commence vismodegib was made. During treatment with vismodegib, she had a perforated gastrointestinal ulcer and required an emergency laparotomy. Vismodegib was stopped, but over the next few years, her BCCs progressed again to an excess of 50 BCCs, including large plaques of carcinoma measuring up to 12 cm in diameter. Vismodegib was restarted with a high-dose proton–pump inhibitor cover, as recommended by the gastroenterology team, and her BCCs were largely resolved. However, a second bleed occurred approximately 1 year after restarting treatment. Gastroscopies undertaken following these episodes were largely normal, showing mild, nonerosive duodenitis only, and Helicobacter pylori testing was negative. Given the lack of pre-existing risk factors and temporal relation to vismodegib therapy, the decision was made to suspend the drug. To our knowledge, this is the first case reported in the literature of UGIB associated with vismodegib. A separate case has reported colonic mucosal changes in a patient with chronic diarrhoea on vismodegib. The hedgehog protein and RNA expression have been found to be present in the gastrointestinal endothelium and mesenchyme. Evidence suggests the hedgehog pathway activation in gastrointestinal lining is involved in the wound-healing response, endothelial turnover and activation of mesenchymal immune responses. Therefore, inhibition of the hedgehog pathway via vismodegib could potentially impair the essential maintenance of the gastrointestinal endothelium. We postulate that this mechanism could have led to the presentation in our patient, through endothelial damage exposure of vessels leading to gastrointestinal bleeding. Treatment options for BCC in our patient are now limited. Vismodegib is one of the few therapies that has been shown to induce remission of symptoms and reduce disease burden. We present this case to raise awareness of this potential adverse event.
BH08 A clinical case of retronychia, a rarely described post-traumatic proximal ingrown nailplate: a condition of the ‘nail’
Authors: Cathcart Charles , Walker-Date Sarah , Belgi Avinash , Jeyakanth Prashanthi
Published: June 2023

Retronychia is a recently described inflammatory disorder that leads to proximal ingrowth of the nail and paronychia. There are fewer than 100 published cases of retronychia, leading to a poor understanding of the disorder and a delay in diagnosis and treatment. Increased understanding for clinicians will be critical in avoiding misdiagnosis and effective management (Costa TPE. Retronychia: a paradigm shift? Skin Appendage Disord 2020; 6:268–71). A 36-year-old woman presented to dermatology with a near three-decade history of treatment-resistant painful, thickened yellow nails of both greater toes. Past medical history included bilateral bunions since the age of 14 years, which were surgically corrected. In the community, she had undergone partial nail avulsion by chiropodists. Subsequently, she received multiple courses of antifungal lacquer and oral terbinafine, all with no effect, and continued regrowth of abnormal thickened nails. On examination of her greater toes, the proximal nailfolds lacked cuticles. The nails showed horizontal ridges, were thickened by stacking of nailplates and had a yellow discoloration. Investigations for fungal nail were negative. A clinical diagnosis of retronychia was made. Retronychia was first recognized in 1999 and is a combination of nailplate ingrowth into the proximal nailfold and the generation of multiple misaligned proximal nailplate lamellae. It is more common in women, typically affects the great toes and is triggered by repetitive microtrauma related to sports, inadequate footwear or, in this case, bunions (de Berker D, Richert B, Duchard E et al. Retronychia: proximal ingrowing of the nail plate. J Am Acad Dermatol 2008; 58:978–83). As in this case, most patients are inadequately treated with antifungals and antibiotics, perhaps due to signs of paronychia resulting in treatment failure and significant psychological impact. If cases are recognized early, conservative management with topical steroids applied to the proximal nailfold is effective. In advance cases, as with this patient, surgical nailplate avulsion with nail matrix ablation is the only curative management. Awareness of the clinical signs would be a valuable learning point for clinicians.
BH13 Is this dissecting cellulitis of the scalp in a White child?
Authors: Khan Farishta , Peng Chenjing
Published: June 2023

Dissecting cellulitis of the scalp (DCS) is characterized by recurrent pustules and sinus tract formation leading to scarring and alopecia. Follicular obstruction is a key pathogenic event and is associated with hidradenitis suppurativa and acne conglobate. Commonly, DCS is found in adult men of Afro-Caribbean descent (Arneja J, Vashi C, Gursel E, Lelli J. Management of fulminant dissecting cellulitis of the scalp in the pediatric population: case report and literature review. Can J Plast Surg 2007; 15:211–14). We describe a rare case of a White child who presented with features suggestive of DCS. An 11-year-old boy was referred with a 2-year history of patches of alopecia affecting the occipital scalp which was initially treated as tinea capitis with antifungal creams, but this was ineffective. On examination, there was diffuse, boggy subcutaneous swelling with scarring, overlying erythema and patches of alopecia on the occipital scalp. A course of erythromycin and oral terbinafine showed a partial response of the affected areas, although subsequent new patches of alopecia were noted with a similar manifestation of bogginess and overlying erythema. Systemic examination, blood tests and skin scrapings were unremarkable. While continuing erythromycin, he was counselled for isotretinoin and a referral to a tertiary centre has been made to guide further management. Paediatric scarring alopecia encompasses congenital and acquired causes (Imhof R, Cantwell H, Proffer S et al. The spectrum of pediatric scarring alopecia: a retrospective review of 27 patients seen at Mayo Clinic. Pediatr Dermatol 2021; 38:580–4). The differential diagnosis for our patient included tinea capitis causing irreversible alopecia, and being aware of this phenomenon with late presentations and delayed treatment is vital. Other differentials are discoid lupus and cutaneous morphoea. However, the clinical features in this case are more in keeping with DCS, which is scarcely reported in the paediatric literature. Histological confirmation is not always practical with children, and follow-up to assess course of the disease is prudent. Importantly, the discussion of permanent hair loss with a child and parent remains challenging, and clinicians should be aware of the associated psychosocial impact.
PS10 Can an aerobic exercise intervention for patients with psoriasis improve health outcomes and support lifestyle behaviour change?
Authors: Sheppard Rory , Kiat Gan Wei , Onambele-Pearson Gladys , Young Helen
Published: June 2023

Patients with psoriasis do not exercise to the extent recommended for cardiovascular health, due to significant disease-specific barriers, which may augment their increased risk of CVD and metabolic syndrome. Therefore, we developed a bespoke, evidenced-based exercise programme for patients with psoriasis, hypothesizing that it may have utility in the management of psoriasis. Eight patients with psoriasis (32.5 ± 12.02 years old, BMI 26.7 ± 3.3 kg m-2) completed a 20-week physical activity intervention. The first 10 weeks of the intervention comprised two walking sessions per week. Each session was of 1h duration and led by a sports-scientist for small-groups of patients with psoriasis. The volume of exercise per session was calculated so that participants would incrementally progress to heart-healthy levels of exercise over the programme. During weeks 10–20 of the programme, participants engaged in independent activities. Warm-ups, pre-exercise stretching, and cool-downs were incorporated into each of the sports-scientist led sessions. Step counts were recorded using a Newfeel Onwalk 900 pedometer throughout the study. Measurements at pre-, mid-, and post-intervention endpoints (week 0, 10 and 20) included assessment of (i) psoriasis: Psoriasis Area and Severity (PASI); Physicians Global Assessment (PGA); (ii) quality of life: Dermatology Life Quality Index (DLQI), Short Form 36 (SF-36); and (iii) cardiometabolic disease/risk – pulse wave velocity (PWV); blood pressure (BP); body weight and BMI. In addition, cardiorespiratory fitness (CRF) was assessed by: 30-s sit-to-stand (30STS); timed up and go (TUG); single leg balance (SLB); static body-weight wall-squat (SBWS); and step count. Recruitment to the study is ongoing. We observed a significant reduction in both Psoriasis Area and Severity Index and systolic BP at the weeks 10 and 20 timepoints (P < 0.05). We also observed a statistically significant improvement in the SF-36 mental health domain between the weeks 10 and 20 timepoints (P = 0.035). The CRF statistically significantly improved across the duration of the study, with a statistically significant improvement in exercise performance, as evidenced by 30STS, TUG and pedometer step counts at week 10 (P < 0.05), SLB between baseline and week 20 (P = 0.043) and SBWS performance across all timepoints. Exercise induces health benefits, including reduced skin inflammation and systolic BP, and increased CRF, and may improve some aspects of quality of life in those with psoriasis. The impact of lifestyle on psoriasis warrants further investigation. Our data suggest that exercise could represent an adjuvant therapy in the future management of psoriasis.
BT06 Using artificial intelligence to triage skin cancer referrals: outcomes from a pilot study
Authors: Abu Baker Karmel , Roberts Elizabeth , Harman Karen , Mullarkey Dan , Kalsi Dilraj
Published: June 2023

Artificial intelligence (AI) is a rapidly emerging field in dermatology, aimed at delivering efficient and effective patient care. To date, there is a lack of substantial evidence for the use of this technology in a clinical setting. However, the pandemic era has placed significant pressures on dermatology services, specifically the skin cancer clinics at our trust, which has experienced a 30% increase in demand compared with prepandemic levels. A novel solution for urgent referrals was to test the use of AI teledermatology software using a UK Conformity Assessed marked Class IIa Medical Device (and therefore regulated by the Medicines and Healthcare products Regulatory Agency). Appropriate cases are selected and booked for a teledermatology appointment at one of our four community-based hubs. Clinical and dermoscopic images, together with a short questionnaire, are uploaded to the software by a healthcare assistant. The AI immediately assesses the dermoscopic images of the lesion, and those cases identified as benign are discharged back to the general practitioner (GP), following a safety check by a consultant dermatologist employed by the AI provider. The trust dermatology consultants have chosen to further triage all cases suspected to be nonbenign. Patients with suitable small lesions at low-risk sites receive a telephone appointment to discuss surgery and obtain consent. Those with precancerous lesions can be discharged back to the GP with management advice. Low-risk basal cell carcinomas case are transferred to a routine pathway. Selected cases may be referred directly to other teams. The pilot started in March 2022 and now processes 5–600 cases per month at four photography hubs. To date, 19% of cases have been discharged back to the GP with a benign diagnosis. A further 15% of cases have been discharged back to the GP by the trust dermatologists, giving an overall discharge rate of 34%. Ten per cent of patients have received a telephone call to take consent for biopsy, and 2% have been referred directly to another speciality. Thirteen per cent of cases have been triaged to a routine pathway, and 38% of patients have required an urgent face-to-face appointment with a dermatologist. The trust has seen > 90% 2-week wait referrals within 2 weeks in the last two quarters. Since the introduction of this AI teledermatology service, we have seen a 62% reduction in the number of patients requiring an urgent face-to-face appointment with a dermatologist. Ongoing audit work is focused on the safety, acceptability and cost-effectiveness of this pathway, and will shape decision-making in the ongoing use of this technology both locally and across the UK.
Hypereosinophilic syndrome presenting with progressive cardiac cachexia: a case report
Authors: Teringová Elena , Penz Peter , Mištinová Jana Poláková , Orban Marek
Published: June 2023

Background

Hypereosinophilic syndrome (HES) is a rare haematologic disorder defined by persistent eosinophilia associated with organ damage. Cardiac involvement occurs in HES patients frequently and represents major cause of their morbidity and mortality.

Case summary

A 66-year-old female patient underwent comprehensive cancer screening due to significant weight reduction. Screening showed negative results except for echocardiography, which revealed a large right ventricular mass imitating malignant cardiac tumour. Patient thus underwent biopsy of the intracardial mass. The procedure was complicated with right ventricular perforation causing cardiac tamponade, successfully resolved by immediate pericardiocentesis. Subsequent echocardiography revealed an echodense mass also in left ventricular apex, resembling a thrombus. Laboratory findings with mildly elevated eosinophil count and presence of formations in both ventricular apexes arose suspicion of non-malignant disease origin, specifically eosinophilic endomyocarditis. The presumption was supported by medical history of bronchial asthma, pansinusitis, and hypereosinophilia. Cardiac magnetic resonance (CMR) confirmed signs of eosinophilic endomyocarditis of both ventricles, together with presence of several intracardiac thrombi. However, despite intensive treatment, patient died due to progressive heart failure 3 months later.

Discussion

As seen in our case, establishing diagnosis of eosinophilic endomyocarditis may represent a challenge in clinical practice, since it represents a rare disease with variable clinical manifestations. However, presence of formations in both ventricles together with peripheral eosinophilia should raise suspicion of this diagnosis. Our case also highlights the importance of CMR imaging in diagnostic process of eosinophilic endomyocarditis, since it represents a non-invasive diagnostic modality able to detect distinctive signs of eosinophilic endomyocarditis.
Antagonic effect of ghrelin and LEAP-2 on hepatic stellate cell activation and liver fibrosis in obesity-associated nonalcoholic fatty liver disease
Authors: Ezquerro Silvia , Tuero Carlota , Becerril Sara , Valentí Víctor , Moncada Rafael , Landecho Manuel F , Catalán Victoria , Gómez-Ambrosi Javier , Mocha Fátima , Silva Camilo , Hanley Karen Piper , Escalada Javier , Frühbeck Gema , Rodríguez Amaia
Published: June 2023

Background

Growing evidence suggests the key role of ghrelin in the onset and progression of nonalcoholic fatty liver disease (NAFLD). The potential participation of ghrelin and the ghrelin receptor antagonist, LEAP-2, in the onset of liver fibrosis in patients with severe obesity and NAFLD through the regulation of TGF-β1-induced hepatic stellate cell (HSC) activation was investigated.

Methods

Circulating (n = 179) and hepatic expression (n = 95) of ghrelin and LEAP-2 were measured in patients with severe obesity and available liver pathology analysis undergoing Roux-en-Y gastric bypass (RYGB). The effect of ghrelin isoforms and LEAP-2 on TGF-β1-induced HSC activation, fibrogenic response, and contractile properties was evaluated in vitro in human LX-2 cells.

Results

Plasma and hepatic ghrelin were negatively associated, while LEAP-2 exhibited a positive association with liver fibrosis in patients with obesity and NAFLD. Six months after RYGB, hepatic function was improved and, although acylated ghrelin and LEAP-2 concentrations remained unchanged, both hormones were inversely related to post-surgical levels of profibrogenic factors TGF-β1 and TIMP-1. Acylated ghrelin treatment reversed TGF-β1-induced myofibroblast-like phenotype, collagen contractile properties, and the upregulation of factors involved in HSC activation and fibrogenesis via PI3K/Akt/mTOR pathway. Moreover, acylated ghrelin inhibited the mild HSC activation induced by LEAP-2.

Conclusions

Ghrelin is an anti-fibrogenic factor blocking HSC activation induced by the most potent fibrogenic cytokine, TGF-β1, and LEAP-2. The imbalance between acylated ghrelin and ghrelin receptor antagonist LEAP-2 might contribute to maintain liver fibrosis in patients with obesity and NAFLD.
Life Course Socioeconomic Position and Cognitive Aging Trajectories: A Cross-National Cohort Study in China and England
Authors: Ruiz Milagros , Hu Yaoyue , Martikainen Pekka , Bobak Martin
Published: June 2023

Background and Objectives

Cross-national research on cognitive aging inequality has largely concentrated on Western countries. It is unclear whether socioeconomic position (SEP) has similar effects on cognitive decline in emerging economies. We compared the association between life course SEP and cognitive function trajectories between China and England, the largest nation under state socialism and one of the oldest capitalist countries.

Research Design and Methods

This cross-cohort study examined participants aged 50 years and older from the China Health and Retirement Longitudinal Study (n = 12,832) and the English Longitudinal Study of aging (n = 8,875). Cognition z-scores were derived using comparable measures of memory and time orientation on 4 occasions. Life course SEP was self-reported by participants at baseline. Seven- to 8-year trajectories of cognition z-scores were estimated using latent growth curve modeling. Country- and gender-specific associations between childhood/adolescent deprivation, education, material wealth, and home ownership were evaluated in relation to model intercept (baseline level) and linear slope (annual rate of change) of cognition.

Results

After multivariable adjustment, education was positively associated with the greatest differences in baseline cognition across country and gender. Education was further linked to a slower rate of cognitive decline (z-score units per year); but compared with those with low education, Chinese men (b = 0.032) and women (b = 0.065) with high education had significantly slower declines than English men (b = −0.004) and women (b = 0.010) with high education.

Discussion and Implications

Despite substantial between-cohort differences in downstream and upstream determinants of dementia, education provided the greatest benefits to cognitive aging in England but particularly in China.
Assessing the in vivo efficacy of rational antibiotics and combinations against difficult-to-treat Pseudomonas aeruginosa producing GES β-lactamases
Authors: Abouelhassan Yasmeen , Gill Christian M , Nicolau David P
Published: June 2023

Objectives

We evaluated the in vivo efficacy of human-simulated regimens (HSRs) of cefiderocol, ceftazidime/avibactam, meropenem and ceftazidime/avibactam/meropenem combination against Guiana-extended spectrum (GES)-producing Pseudomonas aeruginosa isolates.

Methods

Eighteen P. aeruginosa isolates producing GES-1 (n = 5), GES-5 (n = 5) or miscellaneous GESs (combinations of GES-19, GES-20 and/or GES-26; n = 8) were evaluated. In vitro MIC testing was determined using broth microdilution. In a validated murine thigh infection model, HSRs of cefiderocol 2 g q8h as a 3 h IV infusion, ceftazidime/avibactam 2.5 g q8h as a 2 h IV infusion, meropenem 2 g q8h as a 3 h IV infusion or ceftazidime/avibactam/meropenem were administered. Change in bacterial burden relative to baseline and the proportion of isolates in each genotypic group meeting 1-log10 kill endpoint were assessed.

Results

Modal MICs (mg/L) ranged from 0.125 to 1 for cefiderocol, 4 to >64 for ceftazidime/avibactam and 2 to >64 for meropenem. Cefiderocol produced >1-log10 of kill against all 18 tested isolates. Meropenem was active against all GES-1 isolates whereas activity against GES-5 and miscellaneous GESs was lacking, consistent with the MICs. Ceftazidime/avibactam was active against all GES-1 and GES-5 isolates and retained activity against 62.5% of miscellaneous GESs including isolates with elevated MICs. For isolates where ceftazidime/avibactam failed, the addition of meropenem restored the in vivo efficacy.

Conclusions

As monotherapy, cefiderocol was active in vivo against all tested isolates. The activities of meropenem or ceftazidime/avibactam alone were variable; however, a combination of both was active against all isolates. Cefiderocol and ceftazidime/avibactam/meropenem could be valuable therapeutic options for GES-producing P. aeruginosa infections. Clinical confirmatory data are warranted.
Uropathogenic Escherichia coli population structure and antimicrobial susceptibility in Norfolk, UK
Authors: Carter Cailean , Hutchison Alexandra , Rudder Steven , Trotter Elizabeth , Waters Emma V , Elumogo Ngozi , Langridge Gemma C
Published: June 2023

Background

Urinary tract infections (UTIs) are a frequent cause for visits to primary care providers. In alignment globally, uropathogenic Escherichia coli (UPEC) are the main aetiological agent for UTIs in Norfolk and are increasingly difficult to treat due to multi-drug resistance.

Objectives

We set out to identify which clonal groups and resistance genes are disseminating in the community and hospitals in Norfolk, the first study of its kind for UPEC in this region.

Methods

We collected 199 clinical E. coli isolates causing UTIs in the community and hospital from the Clinical Microbiology laboratory at Norfolk and Norwich University Hospital between August 2021 and January 2022. These were whole-genome sequenced using the Illumina and MinION platforms for in silico MLST and antibiotic resistance determinant detection.

Results

The isolates were composed of 70 STs; 8 lineages represented 56.7% of this population: ST73, ST12, ST69, ST131, ST404, ST95, ST127 and ST1193. Importantly, primary UTI screening deemed 6.5% of isolates to be multidrug resistant (MDR), with high rates of resistance to ampicillin (52.1%) and trimethoprim (36.2%) in hospitals. Of concern is the probable clonal expansion of MDR groups ST131 and ST1193 in hospitals and community settings with chromosomally encoded blaCTX-M-15, blaOXA-1 and aac(6′)-Ib-cr5.

Conclusions

The burden of reported UTIs in Norfolk is largely caused by non-MDR isolates and mirrors similar UPEC studies nationally and internationally. Continually monitoring samples with consideration of sources will help reduce burden of disease.
Persistence of the Staphylococcus aureus epidemic European fusidic acid-resistant impetigo clone (EEFIC) in Belgium
Authors: Deplano Ariane , Hallin Marie , Bustos Sierra Natalia , Michel Charlotte , Prevost Benoit , Martiny Delphine , Yin Nicolas
Published: June 2023

Objectives

In August 2018, a public health alert was issued in Belgium regarding clusters of impetigo cases caused by the epidemic European fusidic acid-resistant impetigo clone (EEFIC) of Staphylococcus aureus. As a result, the Belgian national reference centre (NRC) was commissioned to update the epidemiology of S. aureus causing community-onset skin and soft tissues infection (CO-SSTI) to assess the proportion of EEFIC among them.

Methods

For 1 year, Belgian clinical laboratories were asked to send their first three S. aureus isolated from CO-SSTI each month. Isolates were tested for antimicrobial susceptibility to oxacillin, mupirocin and fusidic acid. Resistant isolates were also spa typed and tested for the presence of the genes encoding the Panton–Valentine leucocidin, the toxic shock syndrome toxin and the exfoliatins A and B. MLST clonal complexes were deduced from the spa types.

Results

Among the 518 S. aureus strains analysed, 487 (94.0%) were susceptible to oxacillin. Of these, 79 (16.2%) were resistant to fusidic acid, of which 38 (48.1%) belonged to the EEFIC. EEFIC isolates were mostly isolated from young patients with impetigo and showed a seasonal late summer peak.

Conclusions

These results suggest the persistence of EEFIC in Belgium. Furthermore, its prevalence may lead to reconsideration of the treatment guidelines for impetigo.
Primary Health Care and Foreign Aid: A Tale of Two Germanys
Authors: Bruchhausen Walter , Borowy Iris
Published: June 2023

The Declaration of Alma-Ata remains one of the momentous documents of public health. Its origins lie both in postwar efforts to improve population health in low-income countries and in social medicine promoted decades earlier in Europe. For industrialized countries in East and West, Alma-Ata, therefore, should have provided health-related guidelines both for domestic and foreign policy, though political interpretations of the social components of medicine and health differed. Due to its unique history of ideologically informed division after 1945, Germany forms a fascinating case study.

Important German contributions to the early social medicine discourse fed into ideas of primary health care, the basis of the Alma-Ata process. However, the concept found little resonance in domestic policies. After World War II, the two Germanys chose different paths for health systems but were similarly reluctant to address the social dimension of health in their cooperation with Africa, Asia, and Latin America. In the 1970s, new international health concepts and civil society discussions about “development aid” caused changes in West German policies. No such discussions took place in the German Democratic Republic (GDR), where Alma-Ata was interpreted as a confirmation of the domestic health system. Thus, ironically, West German health workers pursued a keener policy of principles of social medicine in their partner countries than the GDR government, which considered its role in the global transformation of health care mainly fulfilled by serving as a model.
Oligogalactolipid production during cold challenge is conserved in early diverging lineages
Authors: Barnes Allison C , Myers Jennifer L , Surber Samantha M , Liang Zhikai , Mower Jeffrey P , Schnable James C , Roston Rebecca L
Published: June 2023

Severe cold, defined as a damaging cold beyond acclimation temperatures, has unique responses, but the signaling and evolution of these responses are not well understood. Production of oligogalactolipids, which is triggered by cytosolic acidification in Arabidopsis (Arabidopsis thaliana), contributes to survival in severe cold. Here, we investigated oligogalactolipid production in species from bryophytes to angiosperms. Production of oligogalactolipids differed within each clade, suggesting multiple evolutionary origins of severe cold tolerance. We also observed greater oligogalactolipid production in control samples than in temperature-challenged samples of some species. Further examination of representative species revealed a tight association between temperature, damage, and oligogalactolipid production that scaled with the cold tolerance of each species. Based on oligogalactolipid production and transcript changes, multiple angiosperm species share a signal of oligogalactolipid production initially described in Arabidopsis, namely cytosolic acidification. Together, these data suggest that oligogalactolipid production is a severe cold response that originated from an ancestral damage response that remains in many land plant lineages and that cytosolic acidification may be a common signaling mechanism for its activation.
Early Repolarization Syndrome Leading to Recurrent Cardiac Arrest in a Young Active Duty Patient
Authors: Patel Arjun , Oommen Tiffany , Docekal Jeremy , Harris Danny
Published: June 2023

A previously healthy, active duty 37-year-old male experienced recurrent cardiac arrests because of ventricular fibrillation and polymorphic ventricular tachycardia. Initial evaluation did not reveal a clear ischemic, structural, toxic, or metabolic cause. Close monitoring of telemetry before his third cardiac arrest revealed the cause to be early repolarization syndrome (ERS). In this case, we review the diagnosis, epidemiology, and prognostic significance of early repolarization pattern as it relates to ERS. We also discuss acute and long-term treatment strategies for patients with ERS.
Necrotizing acute pancreatitis with electrocardiogram changes masquerading acute coronary syndrome
Authors: Kumar Nirdosh , Waheed Shahan , Siddiqui Amnah , Tamiz Ahmed
Published: June 2023

Acute pancreatitis (AP) refers to the acute inflammation of the pancreas; however, if there is concurrent necrosis, it is called necrotizing acute pancreatitis (NAP). The diagnosis is sometimes difficult because it might mimic acute coronary syndrome (ACS). We report a case of a 28-year-old male, who presented to the emergency department (ED) with severe epigastric pain, shortness of breath and diaphoresis for 4–5 h. The initial electrocardiogram (ECG) showed marked sinus bradycardia with an incomplete left bundle branch block. Considering the clinical presentation and ECG changes, he was managed as ACS and was rushed to catheterization laboratory for a coronary angiogram, which was reported normal. Subsequently, his serum pancreatic enzymes were elevated, and computed tomography of the abdomen showed NAP. In ED settings, it is difficult to differentiate between the two, particularly when AP presents with ECG manifestations masquerading as ACS.
Spontaneous pregnancy in a case with concurrent uterine artery embolization induced transient premature ovarian failure and Asherman syndrome: a case report
Authors: Tarafdari Azadeh , Vahdani Fahimeh G , Hadizadeh Alireza , Khoshravesh Sahar , Hadizadeh Shiva
Published: June 2023

Premature ovarian insufficiency (POI) is an uncommon cause of infertility in females characterized by hypoestrogenism. Studies have shown that uterine artery embolization (UAE) is associated with POI. Meanwhile, Asherman syndrome (AS) is a rare condition because of intracervical or intrauterine adhesions, which can happen after dilation and curettage. Both these syndromes are causes of amenorrhea and infertility. This case is of a 40-year-old woman who, after cesarean scar pregnancy and subsequent UAE because of uncontrollable vaginal bleeding, developed premature ovarian failure and AS. She underwent hysteroscopic adhesiolysis. She became pregnant with low anti-Müllerian hormone levels. Initial adhesiolysis and intervention in AS can restore uterine endometrium’s ability to host a fetus. Moreover, UAE can cause POI, which might regress to some degree.
Does Online Dating Challenge Gendered Divisions of Household Labor?
Authors: Potarca Gina , Hook Jennifer
Published: June 2023

Online dating has modified how people find and select partners. In addition to outcomes already observed (e.g., exogamy), we argue that by subverting normative dating scripts, online courtship practices may set the course for partnerships that display more egalitarian divisions of routine household labor. This may be particularly true for the married and for lower-educated women, who generally report the least egalitarian allocation of domestic work. Furthermore, we posit that the relationship between meeting context and household labor will be partially explained by the selectivity of those who search for partners online but also by mechanisms specific to online dating that allow for greater relationship quality. We use 2008–2019 German Family Panel (pairfam) data in random-effects regression models to predict sharing of routine housework among women in marital and cohabiting opposite-sex unions (N = 3305). We find that meeting online is associated with greater sharing of housework for married women with lower-education, and that the link is robust even after accounting for observed selection into online dating via entropy balancing weights. Contrary to expectations, partnership quality has no mediating effect. Much of the positive association remains unexplained, suggesting that the different ways men and women negotiate power in the dating phase in digital versus non-digital partner markets may indeed play a role in how gender is enacted later on.
E2F7 drives autotaxin/Enpp2 transcription via chromosome looping: Repression by p53 in murine but not in human carcinomas
Authors: Lin Kuan‐Hung , Lee Sue Chin , Dacheux Mélanie A. , Norman Derek D. , Balogh Andrea , Bavaria Mitul , Lee Hsinyu , Tigyi Gabor
Published: June 2023

Dysregulation of the autotaxin (ATX, Enpp2)‐lysophosphatidic acid (LPA) signaling in cancerous cells contributes to tumorigenesis and therapy resistance. We previously found that ATX activity was elevated in p53‐KO mice compared to wild‐type (WT) mice. Here, we report that ATX expression was upregulated in mouse embryonic fibroblasts from p53‐KO and p53R172H mutant mice. ATX promoter analysis combined with yeast one‐hybrid testing revealed that WT p53 directly inhibits ATX expression via E2F7. Knockdown of E2F7 reduced ATX expression and chromosome immunoprecipitation showed that E2F7 promotes Enpp2 transcription through cooperative binding to two E2F7 sites (promoter region −1393 bp and second intron 996 bp). Using chromosome conformation capture, we found that chromosome looping brings together the two E2F7 binding sites. We discovered a p53 binding site in the first intron of murine Enpp2, but not in human ENPP2. Binding of p53 disrupted the E2F7‐mediated chromosomal looping and repressed Enpp2 transcription in murine cells. In contrast, we found no disruption of E2F7‐mediated ENPP2 transcription via direct p53 binding in human carcinoma cells. In summary, E2F7 is a common transcription factor that upregulates ATX in human and mouse cells but is subject to steric interference by direct intronic p53 binding only in mice.
COPD and biologic treatment: state of the art
Authors: Ferri Sebastian , Paoletti Giovanni , Pelaia Corrado , Heffler Enrico , Canonica Giorgio Walter , Puggioni Francesca
Published: June 2023

Purpose of review

Chronic Obstructive Pulmonary Disease (COPD) is a common, heterogeneous disease associated with abnormal inflammatory response of the lung to noxious particles and gases. The progression of disease leads to respiratory failure, disability and premature death. Although recent progress in reducing the global burden of many chronic disease, such as heart disease and cancer, mortality and morbidity due to COPD continue to increase despite of cigarette smoking worldwide policy. Additionally, diagnostic and therapeutic options have not changed in decades. While patients affected by other respiratory disease may benefit with a personalized precision medicine, thanks to the new biological treatment, to date, there is no biological treatment available for COPD. COPD is generally a neutrophils-predominant disease but approximately 40% of patients with COPD had also an eosinophilic airway inflammation.

Recent findings

different Phase III trials have been recently performed to evaluate the efficacy and safety of several biological treatments, mostly against eosinophilic inflammation and, to date, some of this trial, still ongoing have promising results.

This review resumes the rationale, the attempts of biological treatment in COPD and latest promising results.
Highlights of the treatment of allergic rhinitis according to Chinese guidelines
Authors: Zhang Min , Ao Tian , Cheng Lei
Published: June 2023

Purpose of review

This review aimed to introduce the pharmacotherapy of allergic rhinitis according to the 2022 updated Chinese guidelines.

Recent findings

Despite recent advances in basic and clinical research worldwide, pharmacotherapy remains a mainstream in allergic rhinitis treatment. Usually, the first-line drugs, involving intranasal corticosteroids, second-generation oral and intranasal H1-antihistamines, or leukotriene receptor antagonists, can achieve acceptable outcomes in the treatment of allergic rhinitis. The second-line drugs, such as oral corticosteroids, intranasal decongestants and intranasal anticholinergics, can assist in controlling severe symptoms, like nasal congestion/blockage and watery rhinorrhea. For those with moderate-to-severe allergic rhinitis, evidence-based stepwise strategies are suitable, in which the types and dosages of drugs are de-escalated or upgraded according to their therapeutic efficacy. Meanwhile, omalizumab, a novel biological agent, has burgeoned to satisfy the need of patients.

This review highlights the staples in Chinese guidelines about the pharmacotherapy for allergic rhinitis to better understand the guidelines and promote the clinical practice.
Clinical outcomes of AIT in the elderly population
Authors: Bożek Andrzej
Published: June 2023

Purpose of review

This review aims to present the current knowledge on the effectiveness and safety of allergen immunotherapy (AIT) in patients over 60 years of age with inhalant allergies.

Recent findings

Over the last 10 years, the problem of immunoglobulin E allergy in seniors has been noticed by many authors. At the same time, in the 1990s, trials of desensitization to selected inhalant allergens were started, obtaining evidence of the effectiveness of AIT, both with the use of sublingual immunotherapy (SLIT) and injection immunotherapy (SCIT), in patients over 60 years of age with allergic rhinitis. Such data have been confirmed for AITs for grasses, birch, and house dust mites. Currently, these patients are being monitored to assess the long-term effect of AIT. All available observations confirm the high safety of AIT in seniors.

Seniors with allergic rhinitis or asthma may qualify for AIT if they do not have contraindications. These patients can experience a sustained clinical benefit even after completing AIT treatment. Studies indicate that injectable and sublingual routes of administration may be effective in this age group, provided the suspect allergen is accurately diagnosed.
Presence of Preoperative Neurodegeneration Biofluid Markers in Patients with Postoperative Delirium
Authors: Leung Jacqueline M. , Rojas Julio C. , Tang Christopher , Chan Brandon , Lario-Lago Argentina , Boxer Adam L. , Do Quyen , Kramer Joel H. , Du Zhiyuan , Du Pang , Sands Laura P. ,   Perioperative Medicine Research Group
Published: June 2023

Background

The pathophysiology of delirium is incompletely understood, including what molecular pathways are involved in brain vulnerability to delirium. This study examined whether preoperative plasma neurodegeneration markers were elevated in patients who subsequently developed postoperative delirium through a retrospective case-control study.

Methods

Inclusion criteria were patients of 65 yr of age or older, undergoing elective noncardiac surgery with a hospital stay of 2 days or more. Concentrations of preoperative plasma P-Tau181, neurofilament light chain, amyloid β1-42 (Aβ42), and glial fibrillary acidic protein were measured with a digital immunoassay platform. The primary outcome was postoperative delirium measured by the Confusion Assessment Method. The study included propensity score matching by age and sex with nearest neighbor, such that each patient in the delirium group was matched by age and sex with a patient in the no-delirium group.

Results

The initial cohort consists of 189 patients with no delirium and 102 patients who developed postoperative delirium. Of 291 patients aged 72.5 ± 5.8 yr, 50.5% were women, and 102 (35%) developed postoperative delirium. The final cohort in the analysis consisted of a no-delirium group (n = 102) and a delirium group (n = 102) matched by age and sex using the propensity score method. Of the four biomarkers assayed, the median value for neurofilament light chain was 32.05 pg/ml for the delirium group versus 23.7 pg/ml in the no-delirium group. The distribution of biomarker values significantly differed between the delirium and no-delirium groups (P = 0.02 by the Kolmogorov–Smirnov test) with the largest cumulative probability difference appearing at the biomarker value of 32.05 pg/ml.

Conclusions

These results suggest that patients who subsequently developed delirium are more likely to be experiencing clinically silent neurodegenerative changes before surgery, reflected by changes in plasma neurofilament light chain biomarker concentrations, which may identify individuals with a preoperative vulnerability to subsequent cognitive decline.

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Brainstem Modulation of Nociception by Periaqueductal Gray Neurons Expressing the μ-Opioid Receptor in Mice
Authors: Nguyen Eileen , Chiang Michael C. , Nguyen Catherine , Ross Sarah E.
Published: June 2023

Background

Pharmacologic manipulations directed at the periaqueductal gray have demonstrated the importance of the μ-opioid receptor in modulating reflexive responses to nociception. The authors hypothesized that a supraspinal pathway centered on neurons in the periaqueductal gray containing the μ-opioid receptor could modulate nociceptive and itch behaviors.

Methods

The study used anatomical, optogenetic, and chemogenetic approaches in male and female mice to manipulate μ-opioid receptor neurons in the periaqueductal gray. Behavioral assays including von Frey, Hargreaves, cold plantar, chloroquine-induced itch, hotplate, formalin-induced injury, capsaicin-induced injury, and open field tests were used. In separate experiments, naloxone was administered in a postsurgical model of latent sensitization.

Results

Activation of μ-opioid receptor neurons in the periaqueductal gray increased jumping (least-squares mean difference of –3.30 s; 95% CI, –6.17 to –0.44; P = 0.023; n = 7 or 8 mice per group), reduced itch responses (least-squares mean difference of 70 scratching bouts; 95% CI, 35 to 105; P < 0.001; n = 8 mice), and elicited modestly antinociceptive effects (least-squares mean difference of –0.7 g on mechanical and –10.24 s on thermal testing; 95% CI, –1.3 to –0.2 and 95% CI, –13.77 to –6.70, and P = 0.005 and P < 0.001, respectively; n = 8 mice). Last, the study uncovered the role of the periaqueductal gray in suppressing hyperalgesia after a postsurgical state of latent sensitization (least-squares mean difference comparing saline and naloxone of –12 jumps; 95% CI, –17 to –7; P < 0.001 for controls; and –2 jumps; 95% CI, –7 to 4; P = 0.706 after optogenetic stimulation; n = 7 to 9 mice per group).

Conclusions

μ-Opioid receptor neurons in the periaqueductal gray modulate distinct nocifensive behaviors: their activation reduced responses to mechanical and thermal testing, and attenuated scratching behaviors, but facilitated escape responses. The findings emphasize the role of the periaqueductal gray in the behavioral expression of nociception using reflexive and noxious paradigms.

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