bluuebunny/crossref_metadata_2025 huggingface dataset:
PD13 Severe cutaneous manifestations in an Indian child with X-linked dominant erythropoietic protoporphyria
Authors: Srinivas Sahana , Moss Celia
Published: June 2023

Erythropoietic protoporphyria (EPP) is usually caused by autosomal dominant mutations in FECH: raised protoporphyrin levels cause itching, burning and erythema after sun exposure, with facial scarring and sometimes liver damage. We report a child with the much rarer X-linked dominant form (XLDPP) and consider reasons for his unusually severe features. A 4-year-old boy living in India presented with long-standing erosions and scarring on the face and sides of the feet, and marked distal onycholysis with subungual hyperkeratosis affecting all nails, suggestive of pachyonychia congenita (PC). There was no relevant family history or parental consanguinity. He was anaemic (haemoglobin 7.2 g dL−1). Genetic testing revealed no variants in PC genes, but there was a hemizygous deletion in ALAS2, c.1706_1709del (p.Glu569GlyfsT er24) reported recurrently in XLDPP. Further review revealed a history of photosensitivity, low vitamin D3 and raised liver enzymes. Measurement of erythrocyte protoporphyrin was not available, but XLDPP was diagnosed on the basis of photosensitivity, liver abnormalities, probable photo-onycholysis and genetic testing. ALAS2 encodes 5-aminolaevulinate synthase, the first enzyme in the haem synthetic pathway. Most ALAS2 mutations block haemoglobin production resulting in sideroblastic anaemia. However, specific deletions, including this one, activate the pathway, increasing protoporphyrin to levels higher than what can be used in haematopoiesis. The manifestations of XLDPP therefore resemble EPP: protoporphyrin accumulation is caused in the former by increased production and in the latter by a block in its conversion to haem. Iron deficiency, common in Indian children, reduces haem production and consequently protoporphyrin utilization, potentially exacerbating the protoporphyrin accumulation caused by XLDPP. In a previous patient with XLDPP and anaemia due to gastrointestinal bleeding, iron therapy successfully lowered red cell protoporphyrin levels (Whatley SD, Ducamp S, Gouya L et al. C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet 2008; 83:408–14). Nail dystrophy has not previously been reported in XLDPP. The appearance here is consistent with photo-onycholysis in a child whose feet are always exposed in sandals. The delay in diagnosing photosensitivity and severity of his skin changes can be attributed to the difficulty in interpreting symptoms in young children and to local conditions where sun exposure is unavoidable. Management here involves iron therapy, photoprotection, monitoring of liver function and genetic counselling; female carriers may also have symptoms. We are grateful to national experts for helpful discussion of this case.
PD14 Audit of urgent phototherapy referrals
Authors: Dissanayake Perera Apeksha Shyamalie , Rajasekaran Amirtha
Published: June 2023

The British Association of Dermatologists’ (BAD) phototherapy guidelines state that patients referred urgently for phototherapy should start treatment within 3 weeks of referral and that if the patient is considered to require treatment urgently, then it should be started as soon as possible, to reduce patient discomfort and avoid the need for hospital admission. The prepandemic waiting time for urgent referrals, according to an audit in March 2021, was 6 weeks, but this time was even longer postpandemic. During the COVID-19 pandemic lockdown, the phototherapy service was suspended and then resumed in reduced capacity in our unit. The pandemic is also likely to have affected disease severity and patient’s concerns about treatment with systemic options. Our audit objective was to identify the time taken between referral to treatment start time for urgent referrals. Secondary objectives were to identify whether there was any prevalence of certain disease categories in deciding upon urgent referrals, and to identify if severity assessment scores were checked prior to urgent referrals by referring clinicians as per local guidelines. The audit was conducted retrospectively by including all urgent phototherapy referrals for 6 months between January and June 2022. Sixty-four urgent referral forms were analysed. The time taken between referral to treatment start time was 12 months. The majority of the urgent referrals (73%) were for eczema, 16% for psoriasis and 5% for mycosis fungoides. Other conditions such as polymorphic light eruptions, lichen planus and macular amyloidosis totalled 6% of referrals. Only 26% of referrals had documented disease severity scores. Thirty per cent of the referrals were < 18 years of age; young adults (19–25 years) accounted for 19% of referrals. Time taken between referral to treatment start time was 12 months, which significantly exceeded BAD standards. A number of factors affected this, including the impact of the COVID-19 lockdown on services and treatment capacity, patient choices and escalation of disease severity in lockdown, increased referrals with severe skin disease, preference in certain age groups such as children, and psychosocial factors. Patients with severe skin disease needing urgent treatment should be carefully triaged to receive treatment urgently, to avoid admission. Clinicians should assess this appropriately on a case-by-case basis and document disease severity scores and impact of skin disease in all urgent referrals.
PS06 The beast beneath the blisters: assessment of depression and anxiety in patients with immunobullous disorders in a tertiary referral centre
Authors: Ryan Sarah , Lee Eunice , Salih Hamisha , Radcliffe Jenny , DeGiovanni Claudia
Published: June 2023

Immunobullous diseases can be disabling in the acute phase, causing widespread painful or pruritic skin and mucosal lesions. The subsequent psychological consequences of these disorders have not been fully evaluated. We treated a 53-year-old woman for severe bullous pemphigoid affecting her skin and oral mucosa. Following resolution of disease, she was left with debilitating anxiety and depression. This case prompted us to look at the psychological impact of immunobullous disease in our cohort. We used the Patient Health Questionnaire (PHQ-9), General Anxiety Disorder (GAD-7) and Dermatology Life Quality Index to establish the psychosocial impact in patients attending the immunobullous specialist clinic at a large tertiary dermatology centre. An assessment of pain using a numerical pain-rating scale and a question regarding any pre-existing mental health conditions were included. Twelve patients with various immunobullous conditions were surveyed. Seventy-five per cent (n = 9) of patients were identified as having a mood disorder via their PHQ-9 and GAD-7 scores. The PHQ-9 scores indicated mild (50%), moderate (17%) and severe (8%) depression symptoms in these patients. Twenty-five per cent and 17% of patients had a GAD-7 score indicating mild and moderate anxiety, respectively. Three patients declared that they had a previous mental health diagnosis; however, only mild depression and mild anxiety were identified in two of these patients. Only one of these patients volunteered mental health symptoms during their consultation, indicating an unrecognized burden of disease in this community. Our findings support previous research indicating high rates of depression in patients with immunobullous disease. Furthermore, there is an established association between bullous pemphigoid and neuropsychiatric conditions, with identification of autoantigen expression in the central nervous system. Mood disorders have a significant effect on patients’ experience of disease, and are likely to have an impact on disease course and engagement with treatment. A large European study found that dermatologists underestimate the severity of mood disorders. Therefore, the incorporation of validated measures for assessment of mood disorders such as PHQ-9 and GAD-7 into clinical practice is essential to identify the high proportion of patients with immunobullous disease suffering from these disorders. Quality of life measures, which are commonly assessed, are not sufficient for holistic management of these patients. These findings support the invaluable role of a psychologist within dermatology centres, and appropriate referrals to these services will improve with assessment during clinic consultations.
PS07 Delusional infestation: are delays in access to care adversely affecting patient outcomes? A case series
Authors: Angus Janet , Hutchison Eliza , Davies Jo
Published: June 2023

Delusional infestation (DI) is the fixed, false belief of pathogenic infestation of the skin or body, despite no supporting medical evidence. Patients may be difficult to treat successfully, because of their reluctance to accept referral or involvement of psychiatric services. Research consistently supports assessment of this cohort in multidisciplinary psychodermatology clinics, where integrated medical and psychiatric care can be seamlessly provided. The British Association of Dermatologists (BAD) All Parliamentary Group has recommended increased psychodermatology services across the UK, but provision is still scanty. We report a review of 49 consecutive patients (12 men and 37 women) with a diagnosis of DI assessed in a regional psychodermatology service. Mean patient age was 63 years (range 41–92). Mean duration of symptoms before attending was 4.9 years. Forty-one (84%) patients complained of living creatures, with the other eight (16%) perceiving fibres or other inanimate objects. Perception of nonliving mater­ial was strongly associated with substance misuse. Low-dose antipsychotics were prescribed in 44 (90%) patients. Risperidone (n = 39; 89%) and olanzapine (n = 5; 11%) were the drugs prescribed. Medications were well tolerated, with no significant adverse side-effects reported. Twenty-three (47%) responded to treatment. Four patients developed full-blown psychotic disorders. We were unable to engage 13 (27%) patients in treatment, and in three (6%), the treatment outcomes were unknown. Responders had a mean time to presentation of 3.7 years vs. nonresponders who had symptoms for an average of 5.9 years. Ten (20%) patients admitted to current or previous substance misuse. Twenty-one (43%) had a history of psychiatric disease. Substance misuse and established psychiatric disorders were associated with poorer engagement and response. Response to treatment and engagement with services is multifactorial. This review demonstrated that delays in presentation are associated with poorer outcomes (Romanov DV, Lepping P, Bewley A et al. Longer duration of untreated psychosis is associated with poorer outcomes for patients with delusional infestation. Acta Derm Venereol 2018; 98:848–54). In 2016, early intervention in psychosis services was introduced as a National Institute for Health and Care Excellence standard in the UK. In psychiatry, there is well-established evidence of the relationship between delays in treatment of psychosis and poorer outcomes. The BAD guidelines have recently been published to encourage more widespread prescribing of low-dose antipsychotics to expedite treatment. Our review highlights that all patients with DI face significant delays to treatment, which may adversely impact or increase the complexity of clinical presentations. This review emphasizes the importance of early assessment and supports the expansion of psychodermatology services.
BT04 Efficient triaging of advice and guidance referrals using teledermatology via the National Health Service Electronic Referral System platform: reporting positive outcomes from the COVID-19 era
Authors: Efstathiadou Anthoula , Beck-Sander Kellen , Woo Wen Ai , Cooper Hywel , Mitchell Charles
Published: June 2023

The provision of teledermatology in National Health Service (NHS) practice has increased markedly over the last decade. The e-Referral System advice and guidance (A&G) is a platform through which teledermatology services can be provided. It was first implemented in our university teaching hospital department in 2016, but extensive use of this system started during the COVID-19 pandemic. Recognizing the practicality of A&G’s ongoing use to triage referrals efficiently, it was made compulsory for all routine referrals to our department in January 2021. We report on A&G triage use on health service outcomes over a 4-year period (June 2019–June 2022). Retrospective analysis of datasets from four timepoints was chosen for comparison: the month of June in 2019, 2020, 2021 and 2022. The main outcomes analysed were total number of A&G requests, number converted to referral, number returned with advice, percentage of discharges at first attendance and referral to treatment (RTT) waiting time performance (defined as percentage of referrals seen in < 18 weeks). The A&G requests increased appreciably over the study period; only 45 requests received in June 2019, increasing to 965 in June 2020 and 1384 in June 2021, and remaining stable (n = 1140) by June 2022. The initial rise was attributable to the COVID-19 pandemic; further increases were due to changing referral pathways. The majority of A&G requests were returned with advice (77.6%, 66.4% and 54.5% in June 2019, 2020 and 2021, respectively), except in June 2022 where 52.2% were converted to referrals. Separate to quantitative analysis, subjective reporting from triaging dermatologists noted improved primary care referral quality (user descriptions, differential diagnoses suggested and treatment options considered), implying educational benefits for referrers, gained from timely and targeted feedback. This was supported by an increasing conversion-to-referral percentage over the period. Triage of referrals allowed the identification of patients requiring advice prior to clinic review, resulting in improved use of clinics. Subsequently, the percentage of referrals discharged after the first clinical encounter decreased from 70% (June 2019) to 29.9% (June 2020), remaining low by June 2022 (37.9%). Concordantly, RTT performance increased from 60.3% in June 2020 to 88.2% 2 years later. The use of A&G to triage all routine referrals has positively impacted on our department’s health service outcomes, noticeably reducing discharges at first attendance and improving RTT performance. We report on these successful outcomes to highlight to other NHS dermatology teams about efficient methods of teledermatology work in an NHS undergoing ever-increasing demands.
BT24 Use of specialist advice and guidance for dermatology services: the importance of high-quality images in reducing double activity
Authors: Schofield Julia , Scharrer Krisztina
Published: June 2023

The use of specialist advice and guidance (A&G), where primary care healthcare professionals request diagnostic and management advice from specialists, is advocated as the ‘front door’ to dermatology services, to optimize referral management. This approach provides the opportunity for a two-way interchange between primary and specialist services, and can facilitate triage to appropriate dermatology services in a timely fashion. For A&G to work effectively, the expectation is that images will accompany the A&G interaction. Ideally, dermoscopic images would accompany skin lesion A&G requests. It is important that the images are of a high enough quality to enable the reviewing clinician to provide a diagnosis and management plan so that ‘double activity’, where an A&G request is reviewed and the patient needs to be seen because of poor-quality images, is avoided. We introduced specialist A&G in August 2021 and developed referral forms for skin lesions. Dermatoscopes were provided to practices. The aim of this study was to review the quality of skin lesion A&G requests and, in particular, to identify whether a diagnosis and management plan was possible based on the information and images provided. Consecutive skin lesion A&G requests were reviewed over a 4-week period, and information was collected on the images accompanying the request and whether the reviewing clinician was able to make a diagnosis and management plan. In total, 160 skin lesion A&G requests were reviewed over the 4-week period. A skin lesion referral form accompanied 42% of the requests, and 92% were accompanied by macroscopic images (42% clearly labelled) and 59.5% by dermoscopic images. In 32% of the requests, it was not possible to make a diagnosis and management plan. This study highlights the fact that the quality of images accompanying A&G skin lesion referrals is often not good enough to make a diagnosis and management plan. Many of these patients will therefore need to be seen for a face-to-face appointment, which leads to ‘double activity’. If A&G services are to work effectively, then it is essential that high-quality images, ideally including dermoscopy images for skin lesions, accompany the A&G requests. Systems need to identify appropriate models to support image-taking services. Such models can be developed locally and might include community image-taking hubs based in agreed primary care settings or community diagnostic centres. A suitably trained workforce needs to be developed to take and send the images.
Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options
Authors: Grander Christoph , Grabherr Felix , Tilg Herbert
Published: June 2023

The prevalence of non-alcoholic fatty liver disease (NAFLD) is continually increasing due to the global obesity epidemic. NAFLD comprises a systemic metabolic disease accompanied frequently by insulin resistance and hepatic and systemic inflammation. Whereas simple hepatic steatosis is the most common disease manifestation, a more progressive disease course characterized by liver fibrosis and inflammation (i.e. non-alcoholic steatohepatitis) is present in 10–20% of affected individuals. NAFLD furthermore progresses in a substantial number of patients towards liver cirrhosis and hepatocellular carcinoma. Whereas this disease now affects almost 25% of the world’s population and is mainly observed in obesity and type 2 diabetes, NAFLD also affects lean individuals. Pathophysiology involves lipotoxicity, hepatic immune disturbances accompanied by hepatic insulin resistance, a gut dysbiosis, and commonly hepatic and systemic insulin resistance defining this disorder a prototypic systemic metabolic disorder. Not surprisingly many affected patients have other disease manifestations, and indeed cardiovascular disease, chronic kidney disease, and extrahepatic malignancies are all contributing substantially to patient outcome. Weight loss and lifestyle change reflect the cornerstone of treatment, and several medical treatment options are currently under investigation. The most promising treatment strategies include glucagon-like peptide 1 receptor antagonists, sodium–glucose transporter 2 inhibitors, Fibroblast Growth Factor analogues, Farnesoid X receptor agonists, and peroxisome proliferator–activated receptor agonists. Here, we review epidemiology, pathophysiology, and therapeutic options for NAFLD.
Impact of Supplementary Immunization Activities using Novel Oral Polio Vaccine Type 2 during a Large outbreak of Circulating Vaccine-Derived Poliovirus in Nigeria
Authors: Voorman Arend , Lyons Hil , Shuaib Faisal , Adamu Usman S , Korir Charles , Erbeto Tesfaye , Bandyopadhyay Ananda S , Okiror Samuel
Published: June 2023

Background

Novel oral poliovirus vaccine (OPV) type 2 (nOPV2) has been made available for outbreak response under an emergency use listing authorization based on supportive clinical trial data. Since 2021 more than 350 million doses of nOPV2 were used for control of a large outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Nigeria.

Methods

Using a bayesian time-series susceptible-infectious-recovered model, we evaluate the field effectiveness of nOPV2 immunization campaigns in Nigeria compared with campaigns using monovalent OPV type 2 (mOPV2).

Results

We found that both nOPV2 and mOPV2 campaigns were highly effective in reducing transmission of cVDPV2, on average reducing the susceptible population by 42% (95% confidence interval, 28–54%) and 38% (20–51%) per campaign, respectively, which were indistinguishable from each other in this analysis (relative effect, 1.1 [.7–1.9]). Impact was found to vary across areas and between immunization campaigns.

Conclusions

These results are consistent with the comparable individual immunogenicity of nOPV2 and mOPV2 found in clinical trials but also suggest that outbreak response campaigns may have small impacts in some areas requiring more campaigns than are suggested in current outbreak response procedures.
Learning to Live with an Unruly Consuming Body
Authors: Bhatnagar Kushagra , Tillotson Jack S , Toyoki Sammy , Laker Benjamin
Published: June 2023

Past research shows that successful consumer learning takes place in environments that support cooperative communities of practice, that enable access to refined didactic resources, and that provide a safe, sympathetic backstage for a controllable and able learning body to durably transition from one repertoire to another. This study complements existing research by investigating a group of lactose-intolerant consumers who must learn to transition to a new consumption repertoire because of socially embarrassing symptoms. Consumers must engage in high-risk, unguided, experiential learning pathways in a less than sympathetic frontstage, without the support of a cooperative community or a well-developed vocabulary, and while grappling with an impaired and unruly body in a dynamic marketplace. The findings demonstrate that consumers adapt to this hostile learning environment by surfing between different consumption repertoires in a fluid, impermanent manner.
CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database
Authors: Kobayashi Kenya , Saito Yuki , Kage Hidenori , Fukuoka Osamu , Yamamura Koji , Mukai Toshiyuki , Oda Katsutoshi , Yamasoba Tatsuya
Published: June 2023

Background

Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed.

Methods

We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher’s exact test, Kaplan–Meier analysis, log-rank test and Cox regression models were used for statistical analysis.

Results

In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P = 0.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P = 0.009) and ARID1A mutations (hazard ratio, 4.029; P = 0.034) were significantly associated with overall survival.

Conclusion

CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.
The room where it happens: addressing diversity, equity, and inclusion in National Clinical Trials Network clinical trial leadership
Authors: Snyder Rebecca A , Burtness Barbara , Cho May , Del Rivero Jaydira , Doroshow Deborah B , Hitchcock Kathryn E , Kalyan Aparna , Kim Christina A , Lukovic Jelena , Parikh Aparna R , Sanford Nina N , Singh Bhuminder , Shen Chan , Shroff Rachna T , Vijayvergia Namrata , Goodman Karyn A , Kunz Pamela L
Published: June 2023

Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups are made up of multidisciplinary investigators who work collaboratively to conduct trials that test novel therapies and establish best practice for cancer care. Unfortunately, disparities in clinical trial leadership are evident. To examine the current state of diversity, equity, and inclusion across the NCTN, an independent NCTN Task Force for Diversity in Gastrointestinal Oncology was established in 2021, the efforts of which serve as the platform for this commentary. The task force sought to assess existing data on demographics and policies across NCTN groups. Differences in infrastructure and policies were identified across groups as well as a general lack of data regarding the composition of group membership and leadership. In the context of growing momentum around diversity, equity, and inclusion in cancer research, the National Cancer Institute established the Equity and Inclusion Program, which is working to establish benchmark data regarding diversity of representation within the NCTN groups. Pending these data, additional efforts are recommended to address diversity within the NCTN, including standardizing membership, leadership, and publication processes; ensuring diversity of representation across scientific and steering committees; and providing mentorship and training opportunities for women and individuals from underrepresented groups. Intentional and focused efforts are necessary to ensure diversity in clinical trial leadership and to encourage design of trials that are inclusive and representative of the broad population of patients with cancer in the United States.
Identification of the perpetrator imperatorin in Xin-yi-san-theophylline interaction: observed and predicted herb-drug interaction in rats
Authors: Wang Hong-Jaan , Chen An-Chi , Chen Hsin-Ying , Cheng Hsin-Chung , Kao Li-Ting , Lu Chung-Kuang , Tsai Keng-Chang , Lee I-Jung , Ueng Yune-Fang
Published: June 2023

Objectives

Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats.

Methods

The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine.

Key findings

XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3–10 fold. In a dose-dependent manner, XYS and imperatorin (0.1–10 mg/kg) treatments significantly decreased theophylline clearance by 27–33% and 19–56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51–112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27–57%) by XYS was moderate.

Conclusions

XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen.
Transcriptional and post-translational regulation of plant autophagy
Authors: Agbemafle William , Wong Min May , Bassham Diane C
Published: June 2023

In response to changing environmental conditions, plants activate cellular responses to enable them to adapt. One such response is autophagy, in which cellular components, for example proteins and organelles, are delivered to the vacuole for degradation. Autophagy is activated by a wide range of conditions, and the regulatory pathways controlling this activation are now being elucidated. However, key aspects of how these factors may function together to properly modulate autophagy in response to specific internal or external signals are yet to be discovered. In this review we discuss mechanisms for regulation of autophagy in response to environmental stress and disruptions in cell homeostasis. These pathways include post-translational modification of proteins required for autophagy activation and progression, control of protein stability of the autophagy machinery, and transcriptional regulation, resulting in changes in transcription of genes involved in autophagy. In particular, we highlight potential connections between the roles of key regulators and explore gaps in research, the filling of which can further our understanding of the autophagy regulatory network in plants.
Intracystic papillary neoplasm diagnosis following an extended cholecystectomy: a case report … and literature review
Authors: Kitasaki Nao , Inoue Masashi , Abe Tomoyuki , Kohata Akihiro , Kochi Masatoshi , Hotta Ryuichi , Kobayashi Tsuyoshi , Ohdan Hideki , Toyota Kazuhiro , Takahashi Tadateru
Published: June 2023

We report a case of intracystic papillary neoplasms (ICPN) that was difficult to differentiate from adenocarcinoma of the gallbladder. A 64-year-old man visited our hospital for an examination of gallbladder tumors. At the preoperative examination, the tumor was revealed a papillary type of tumor in the body of the gallbladder without the findings that without the findings that suggested the tumor invasion into the deep subserosal layer. The patient underwent an extended cholecystectomy. Papillary lesions were observed mainly in the body of the gallbladder, with flattened elevated lesions at the gallbladder fundus. Within each of these tumors, cells corresponding to intraepithelial adenocarcinoma were irregularly interspersed, leading to a diagnosis of ICPN. The patient is currently undergoing follow-up with no recurrence postoperatively. The prognosis of ICPN is generally good; however, preoperative diagnosis remains challenging. Therefore, a treatment plan for gallbladder cancer should be applied.
A rare synchronous of dual primary genitourinary carcinoma manifested with a rapidly progressive renal failure
Authors: Affas Athar , AlBitar Sami , Alyyan Fatemah , Affas Mohammad Nasser
Published: June 2023

Non-urothelial carcinoma accounts for <5% of urinary bladder tumors, and primary bladder adenocarcinoma accounts for 0.5–2%, but the variant primary signet-ring cell is extremely rare. We present a rare case of a synchronous of dual primary malignancy from a rare variant of urinary bladder adenocarcinoma (signet-ring cell) with indolent prostate adenocarcinoma in a 61-year-old male. The patient presented with a rapidly progressive renal failure due to a non-dilated obstructive uropathy that formed a dilemma in the course of diagnosiswhich  was relieved transiently by a high-dose methylprednisolone. Primary signet-ring cell adenocarcinoma of the urinary bladder is a very rare malignancy manifests as a high-grade, high-stage lesion, which takes a vague course and has a poor prognosis. It is often managed with radical cystectomy due to its aggressive nature.

Key messages  Non-dilated urinary obstruction should be considered as a possible rare cause of rapidly progressive renal failure, and often, it is related to an indolent and progressive urinary malignancy.
Pembrolizumab Every 6 Weeks Versus Every 3 Weeks in Advanced Non-Small Cell Lung Cancer
Authors: Dubé-Pelletier Maude , Labbé Catherine , Côté Jimmy , Pelletier-St-Pierre Audrey-Ann
Published: June 2023

Background

The survival benefits and adverse effects of pembrolizumab 2 mg/kg intravenously (IV) every 3 weeks (Q3W) in advanced non-small lung cancer (NSCLC) are well documented in the literature. Based on pharmacokinetic models, a pembrolizumab 4 mg/kg IV every 6 weeks (Q6W) dosing regimen is also approved in some countries. To date, there is no direct comparison in the literature between these 2 regimens in advanced NSCLC.

Methods

This retrospective study included 80 patients with advanced NSCLC who received pembrolizumab monotherapy 4 mg/kg Q6W between March 1, 2020 and December 31, 2021 and 80 patients with advanced NSCLC who received pembrolizumab monotherapy 2 mg/kg Q3W between January 1, 2017 and January 15, 2019 at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). The primary outcomes of this study were to compare overall survival (OS), progression-free survival (PFS) as well as the occurrence and severity of immune-mediated adverse events (AEs) in patients with advanced NSCLC who received pembrolizumab Q6W vs Q3W. Data cutoff date was December 15, 2022.

Results

Median follow-up was 14.5 ± 8.6 months in the Q6W group and 18.3 ± 19.6 months in the Q3W group. Median PFS was 6.9 months (CI 95% 5.0-10.7) in the Q6W group vs 8.9 months (CI 95% 5.6-14.1) in the Q3W group (adjusted HR 1.27 (CI 95% 0.85-1.89), P = .25). Median OS was not reached in the Q6W group vs 20.5 months (CI 95% 13.7-29.8) in the Q3W group (adjusted HR 0.80 (CI 95% 0.50-1.29), P = .36). Immune-mediated AEs of grade ≥ 3 occurred in 18% of patients in the Q6W group and in 19% of those in the Q3W group.

Conclusions

In this unicentric retrospective study, the pembrolizumab Q6W dosing regimen was comparable to the Q3W in terms of OS, PFS, and toxicity.
Hypersensitivity to gadolinium-based contrast
Authors: Sáenz de Santa María Rocío , Labella Marina , Bogas Gádor , Doña Inmaculada , Torres María José
Published: June 2023

Purpose of review

The use of contrast media is increasing in recent decades. Although gadolinium-based contrast agents (GBCAs) are generally well tolerated, adverse reactions, including hypersensitivity reactions (HSRs), although infrequent, may occur. It is important to perform a thorough allergological evaluation in patients with suspected GBCA-HSRs to avoid potentially serious reactions in subsequent exposures.

Recent findings

Data on GBCA-HSRs are scarce. Most published articles dealing with skin tests and drug provocation tests (DPTs) with GBCAs are case series and small cohorts. Controversies exist about the role of premedication for preventing HSRs on subsequent exposures. Selection of well tolerated alternatives is based on potential cross-reactivity among GBCAs; however, the extent of cross-reactivity among them remains unclear.

As premedication is not useful because breakthrough reactions are frequent in patients with GBCA-HSRs in subsequent exposures, an allergological evaluation is required. Available data suggest a high negative predictive value of skin tests, being crucial for guiding the selection of an alternative GBCA. However, DPTs are still necessary to confirm or exclude the diagnosis or find alternative GBCAs. Cross-reactivity is high among GBCAs belonging from the same group, mainly among macrocyclic compounds, so this must be taken into account for selecting alternatives.
Vagueness in Goals-of-Care Conferences for Critically Ill Patients: Types of Hedge Language Used by Physicians*
Authors: Mittal Vaishali , Hakes Nicholas A. , Magnus David , Batten Jason N.
Published: June 2023

OBJECTIVES:

Hedge language is a category of language that refers to words or phrases that make statements “fuzzier.” We sought to understand how physicians use hedge language during goals-of-care conferences in the ICU.

DESIGN:

Secondary analysis of transcripts of audio-recorded goals-of-care conferences in the ICU.

SETTING:

Thirteen ICUs at six academic and community medical centers in the United States.

PATIENTS:

Conferences were between clinicians and surrogates of incapacitated, critically ill adults.

INTERVENTIONS:

Four investigators performed a qualitative content analysis of transcripts using deductive followed by inductive methods to identify types of hedge language used by physicians, then coded all instances of hedge language across 40 transcripts to characterize general patterns in usage.

MEASUREMENTS AND MAIN RESULTS:

We identified 10 types of hedge language: numeric probabilistic statement (“there’s an 80% chance”), qualitative probabilistic statement (“there’s a good chance”), nonprobabilistic uncertainty statement (“hard to say for her”), plausibility shield (“we expect”), emotion-based statement (“we’re concerned”), attribution shield (“according to Dr. X”), adaptor (“sort of”), metaphor (“the chips are stacking up against her”), time reference (“too soon to tell”), and contingency statement (“if we are lucky”). For most types of hedge language, we identified distinct subtypes. Physicians used hedge language frequently in every transcript (median: 74 hedges per transcript) to address diagnosis, prognosis, and treatment. We observed large variation in how frequently each type and subtype of hedge language was used.

CONCLUSIONS:

Hedge language is ubiquitous in physician-surrogate communication during goals-of-care conferences in the ICU and can be used to introduce vagueness to statements in ways beyond expressing uncertainty. It is not known how hedge language impacts decision-making or clinician-surrogate interactions. This study prioritizes specific types of hedge language for future research based on their frequency and novelty.
Risk Factors for Recurrence and the Role of Radiotherapy in Low-grade Myofibroblastic Sarcoma
Authors: Mamikunian Garrett , Ziegler Andrea , Block Alec , Thorpe Eric
Published: June 2023

Low-grade myofibroblastic sarcoma (LGMS) is a rare malignancy that commonly occurs in the head and neck region. The role of radiotherapy has been unclear in treating LGMS and the risk factors for recurrence have remained undefined. The objective of this study is to determine risk factors for the recurrence of LGMS in the head and neck as well as the role of radiotherapy in the treatment of LGMS. A comprehensive review of the literature was performed through Pubmed leading to the inclusion of 36 articles after our inclusion and exclusion criteria were applied. Continuous variables were analyzed with a 2-tail unpaired t test. Categorical variables were assessed with the χ2 test or Fisher exact test. Logistic regression and multivariable logistic regression analysis with 95% CIs were used to obtain odds ratios. LGMS most commonly occurred in the oral cavity (49.2%). Half of all recurrences occurred in the paranasal sinuses/skull base. LGMS occurring at the paranasal sinuses/skull base had a significantly increased risk of recurrence compared with other subsites within the head and neck (odds ratio: −40; 95% CI: 2.190, 762.005; P = 0.013). The average time to recurrence of LGMS was 19.2 months. Adjuvant treatment with radiation did not improve recurrence rates. Sex, tumor size, or bony involvement were not found as risk factors for recurrence. Patients with LGMS of the paranasal sinuses and skull base are at high risk for recurrence and should be monitored closely. The role of adjuvant radiation treatment in these patients remains unclear.
Unusual Behavior of Intestinal Spirochetosis: A Case Report
Authors: Petruzzellis Carlo , Catino Federico
Published: June 2023

Human intestinal spirochetosis is a rare clinicopathological condition characterized by the presence of spirochetal microorganisms on the surface of the colorectal mucosa and, in some cases, by their invasion into the lamina propria. The most frequent cause of this infection is immunocompromised status. Our case report describes a patient with relevant symptoms and endoscopic alterations, but limited invasion by spirochetes, as shown by histological analysis of ileal and colonic specimens. After histological examination, metronidazole was initiated. This resulted in rapid and complete resolution of the symptoms, which demonstrated an infectious etiology. The peculiarity of our case is that the clinical and endoscopic appearances were typical of the aggressive behavior of the disease, but histological samples showed only superficial colonization of the colonic epithelium without clear invasion of deeper layers. This case report emphasizes that the virulence of spirochetes is not strictly related to intestinal mucosal invasion.
Spontaneous reporting of adverse reactions associated with the COVID-19 vaccine in health care professionals: A descriptive observational study conducted in a Portuguese hospital
Authors: Teófilo Vanessa S. G. , Pinho Paulo R. A. , Cordeiro Gonçalo J. , Saldanha Nuno A. F. , Matos Pedro M. M. , Ribeiro Rui A. M. , Moreira Salomé M. , Miller Mariana S. F , Dias Andreia R. M. , Couto Marta F. R. , Norton Pedro M. P. N. S.
Published: June 2023

Background:

The coronavirus disease 2019 (COVID-19) was classified as a pandemic in March 2020 by the World Health Organization. The Pfizer-BioNTech COVID-19 vaccine was the first to be authorized in the European Union, based on data from phase 1, 2, and 3 clinical trials of limited duration. Concerns have been raised regarding the vaccine's safety profile. Some of the adverse drug reactions (ADRs) associated with vaccines may not have been identified during clinical trials. This study aimed to identify ADRs associated with the Pfizer-BioNTech vaccine in health care professionals at a Portuguese tertiary university hospital.

Methods:

The data used in this analysis consist of ADRs reported through a spontaneous notification system from vaccines administered between December 27, 2020, and January 31, 2021. ADRs were categorized according to the MedDRA terminology.

Results:

A total of 8,605 Pfizer-BioNTech vaccines were administered to 4568 health care professionals. ADRs were reported among 520 of the vaccines, with an incidence of 13.56% in women and 5.31% in men. The mean age of the population reporting ADRs was 41.52 years, with a standard deviation of 9.83 years. The most frequent ADRs were myalgia (n = 274), headache (n = 199), pyrexia (n = 164), injection site pain (n = 160), fatigue (n = 84), nausea (n = 81), chills (n = 65), lymphadenopathy (n = 64), and arthralgia (n = 53). Hypersensitivity reactions occurred in 15 health care professionals, with no anaphylactic reactions observed. A total of four Important Medical Events were observed, which consisted of two cases of syncope, one case of sudden hearing loss, and one case of transverse myelitis.

Conclusion:

The vaccine was well-tolerated among the study participants. Reactogenicity was greater after the second dose. The incidence of ADRs was higher in women and individuals aged between 40 to 49 years. Systemic adverse reactions were most frequently reported. Systematic monitoring of ADRs of COVID-19 vaccines in real-life context is essential for a more robust establishment of its safety profile.
Renal Neoplasia Occurring in Patients With PTEN Hamartoma Tumor Syndrome
Authors: Kozman Diana , Kao Chia-Sui , Nguyen Jane K. , Smith Steven C. , Kehr Elizabeth L. , Tretiakova Maria , Przybycin Christopher G. , Williamson Sean R. , Argani Pedram , Eng Charis , Campbell Steven C. , McKenney Jesse K. , Alaghehbandan Reza
Published: June 2023

The aim of this study was to assess the histopathologic spectrum of renal tumors in patients with PTEN hamartoma tumor syndrome (PHTS), with a specific focus on potential features predictive of the underlying syndrome. A multi-institutional study was conducted to obtain clinical and pathologic data on renal tumors arising in patients with PHTS, either diagnosed by germline mutational analysis or clinical criteria for Cowden syndrome. Histologic sections of the renal tumors were re-reviewed for classification. Twelve renal epithelial tumors from 9 patients were identified (4 males and 5 females, with a mean age of 41.8 y), 7 of whom carried germline PTEN mutations. All 12 renal epithelial tumors were renal cell carcinomas (RCCs): 5 were chromophobe RCCs, 4 papillary RCCs, and 3 RCC not otherwise specified. Pathologic stage distribution was: 7 (59%) pT1a, 2 (17%) pT1b, 1 (8%) pT2a, 1 (8%) pT2b, and 1 (8%) pT3a. World Health Organization/International Society of Urological Pathology (WHO/ISUP) histologic grade was applicable in 7 (54%) nonchromophobe tumors: 4 (57%) G2, 2 (29%) G3, and 1 (14%) G4. An unexpected histologic finding was the presence of 2 patients with incidental microscopic collections of intrarenal adipocytes that had no features of angiomyolipoma (and were negative with 2 sensitive PEComa markers: cathepsin-K and GPNMB); both were classified as lipoma/“lipomatous hamartomas.” The average follow-up interval was 67.8 months (13 to 172 mo): 5 patients had no evidence of disease, 2 were lost to follow-up, 1 died of other (non-PHTS) causes (ie, prostate cancer), and 1 was alive with metastatic RCC to the lung (RCC not otherwise specified with rhabdoid differentiation). All tumors showed loss of nuclear PTEN staining by immunohistochemistry. Fumarate hydratase was retained and 2SC was negative in all papillary RCCs. CK7 was moderate-strong/diffuse positive in 4 of 5 chromophobe RCCs and in 3 of 4 papillary RCCs. Renal epithelial tumors associated with PHTS represent a heterogeneous group of RCCs, but classic chromophobe and papillary RCC are most common. The majority have a favorable clinical behavior as would be predicted by subtype. In contrast to other hereditary renal neoplasia syndromes, morphologic features of the RCCs do not allow identification of PHTS-associated neoplasia with any degree of specificity in the absence of clinical setting and/or prior history, but the presence of microscopic “lipomas” within the kidney may provide a clue in rare cases. Therefore, clinical suspicion and genetic counseling with germline testing remain necessary for identifying PHTS-associated RCC.
The Impact of Virtual Humans on Psychosomatic Medicine
Authors: Loveys Kate , Sagar Mark , Antoni Michael , Broadbent Elizabeth
Published: June 2023

Objective

Virtual humans are likely to enhance the delivery of health care over the next decade. Virtual humans are artificially intelligent computer agents with hyperrealistic, autonomously animated embodiments based on affective computing techniques. Virtual humans could be programmed to screen for health conditions, triage patients, and deliver health interventions, with appropriate facial expressions and body gestures, functioning as a supplement to human care. This article provides a perspective on the implications of virtual humans for behavioral and psychosomatic medicine, and health psychology.

Methods

A narrative review was conducted to integrate observations and findings from research on virtual humans from 91 articles in this multidisciplinary area.

Results

Virtual humans can be used for multimodal behavior analysis of patients, individualized tailoring of interventions, and detection of changes of psychological and behavioral measures over time. Virtual humans can also pair the scalability of a website with the interactivity and relational skills of a human tele-therapist. Research is beginning to show the acceptability, feasibility, and preliminary effectiveness of virtual humans in a range of populations. Virtual humans can be easily tailored in terms of their appearance, voice, and language, and may be adapted to fit the characteristics of a patient population or hard-to-reach groups. If co-designed with these communities, virtual humans may help to promote health care engagement and improve outcomes.

Conclusions

Virtual humans can engage and motivate patients, and deliver personalized psychological and behavioral health care. This article provides an overview of the potential impact of virtual humans on psychosomatic medicine and discusses ethical implications.