Bilateral Blistering Rash Following Gastric Bypass Procedure and Mushroom Soup Diet: Hepatitis C Virus-Seronegative Necrolytic Acral Erythema.

Necrolytic acral erythema (NAE) is an uncommon cutaneous disorder characterized by a symmetric acral distribution of erythematous plaques with underlying epidermal necrosis. While typically presenting in the context of hepatitis C virus (HCV) infection, NAE can also present secondary to nutritional deficiency or systemic disease. We present a case of NAE in a 66-year-old patient with no history of HCV infection status post gastric bypass who had a three-month history of eating only mushroom soup. The patient underwent a punch biopsy and was tested for a variety of nutritional deficiencies. Biopsy demonstrated partial necrosis of the upper epidermis, with subjacent re-epithelialization, squamatization, and vacuolopathy of the basal epidermis. He was treated with zinc replacement therapy after initial trials of tacrolimus and clobetasol were unsuccessful. At follow-up, he had significant improvement of the lesions. This case provides an example of an atypical presentation of NAE in the absence of HCV infection that presented as a complication of gastric bypass-associated nutritional deficiency.

Occupational exposure to malaria, leishmaniasis and arbovirus vectors in endemic regions: A systematic review.

Vector-borne diseases, including dengue, leishmaniasis and malaria, may be more common among individuals whose occupations or behaviours bring them into frequent contact with these disease vectors outside of their homes. A systematic review was conducted to ascertain at-risk occupations and situations that put individuals at increased risk of exposure to these disease vectors in endemic regions and identify the most suitable interventions for each exposure. The review was conducted in accordance with PRISMA guidelines on articles published between 1945 and October 2021, searched in 16 online databases. The primary outcome was incidence or prevalence of dengue, leishmaniasis or malaria. The review excluded ecological and qualitative studies, abstracts only, letters, commentaries, reviews, and studies of laboratory-acquired infections. Studies were appraised, data extracted, and a descriptive analysis conducted. Bite interventions for each risk group were assessed. A total of 1170 articles were screened and 99 included. Malaria, leishmaniasis and dengue were presented in 47, 41 and 24 articles, respectively; some articles presented multiple conditions. The most represented populations were soldiers, 38% (43 of 112 studies); refugees and travellers, 15% (17) each; migrant workers, 12.5% (14); miners, 9% (10); farmers, 5% (6); rubber tappers and missionaries, 1.8% (2) each; and forest workers, 0.9% (1). Risk of exposure was categorised into round-the-clock or specific times of day/night dependent on occupation. Exposure to these vectors presents a critical and understudied concern for outdoor workers and mobile populations. When devising interventions to provide round-the-clock vector bite protection, two populations are considered. First, mobile populations, characterized by their high mobility, may find potential benefits in insecticide-treated clothing, though more research and optimization are essential. Treated clothing offers personal vector protection and holds promise for economically disadvantaged individuals, especially when enabling them to self-treat their clothing to repel vectors. Secondly, semi-permanent and permanent settlement populations can receive a combination of interventions that offer both personal and community protection, including spatial repellents, suitable for extended stays. Existing research is heavily biased towards tourism and the military, diverting attention and resources from vulnerable populations where these interventions are most required like refugee populations as well as those residing in sub-Saharan Africa.

Germline ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition.

The genomics era has facilitated discovery of new genes predisposing to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ERG as a novel autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor critical for definitive hematopoiesis, stem cell function and platelet maintenance. ERG colocalizes with other transcription factors including RUNX1 and GATA2 on promoters/enhancers of genes orchestrating hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 thrombocytopenic individuals from one family and 14 additional ERG variants in unrelated individuals with BMF/HM including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germline ERG variants included cytopenias (thrombocytopenia, neutropenia, pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense, 1 truncating) including 3 missense population variants were functionally characterized. Thirteen potentially pathogenic ETS domain missense variants displayed loss-of-function characteristics disrupting transcriptional transactivation, DNA-binding and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture, and to promote acute erythroleukemia when transplanted into mice, concordant with these variants being loss-of-function. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germline ERG variants has clinical implications for patient/family diagnosis, counselling, surveillance, and treatment strategies including selection of bone marrow donors or cell/gene therapy.

Screening of malaria infections in human blood samples with varying parasite densities and anaemic conditions using AI-Powered mid-infrared spectroscopy.

BACKGROUND: Effective testing for malaria, including the detection of infections at very low densities, is vital for the successful elimination of the disease. Unfortunately, existing methods are either inexpensive but poorly sensitive or sensitive but costly. Recent studies have shown that mid-infrared spectroscopy coupled with machine learning (MIRs-ML) has potential for rapidly detecting malaria infections but requires further evaluation on diverse samples representative of natural infections in endemic areas. The aim of this study was, therefore, to demonstrate a simple AI-powered, reagent-free, and user-friendly approach that uses mid-infrared spectra from dried blood spots to accurately detect malaria infections across varying parasite densities and anaemic conditions. METHODS: Plasmodium falciparum strains NF54 and FCR3 were cultured and mixed with blood from 70 malaria-free individuals to create various malaria parasitaemia and anaemic conditions. Blood dilutions produced three haematocrit ratios (50%, 25%, 12.5%) and five parasitaemia levels (6%, 0.1%, 0.002%, 0.00003%, 0%). Dried blood spots were prepared on Whatman™ filter papers and scanned using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) for machine-learning analysis. Three classifiers were trained on an 80%/20% split of 4655 spectra: (I) high contrast (6% parasitaemia vs. negative), (II) low contrast (0.00003% vs. negative) and (III) all concentrations (all positive levels vs. negative). The classifiers were validated with unseen datasets to detect malaria at various parasitaemia levels and anaemic conditions. Additionally, these classifiers were tested on samples from a population survey in malaria-endemic villages of southeastern Tanzania. RESULTS: The AI classifiers attained over 90% accuracy in detecting malaria infections as low as one parasite per microlitre of blood, a sensitivity unattainable by conventional RDTs and microscopy. These laboratory-developed classifiers seamlessly transitioned to field applicability, achieving over 80% accuracy in predicting natural P. falciparum infections in blood samples collected during the field survey. Crucially, the performance remained unaffected by various levels of anaemia, a common complication in malaria patients. CONCLUSION: These findings suggest that the AI-driven mid-infrared spectroscopy approach holds promise as a simplified, sensitive and cost-effective method for malaria screening, consistently performing well despite variations in parasite densities and anaemic conditions. The technique simply involves scanning dried blood spots with a desktop mid-infrared scanner and analysing the spectra using pre-trained AI classifiers, making it readily adaptable to field conditions in low-resource settings. In this study, the approach was successfully adapted to field use, effectively predicting natural malaria infections in blood samples from a population-level survey in Tanzania. With additional field trials and validation, this technique could significantly enhance malaria surveillance and contribute to accelerating malaria elimination efforts.

A photoaging smartphone application to promote sun safety behaviors among youth in late childhood and adolescence.

BACKGROUND: Ultraviolet (UV)-exposure behaviors can directly impact an individual's skin cancer risk, with many habits formed during childhood and adolescence. We explored the utility of a photoaging smartphone application to motivate youth to improve sun safety practices. METHODS: Participants completed a preintervention survey to gather baseline sun safety perceptions and behaviors. Participants then used a photoaging mobile application to view the projected effects of chronic UV exposure on participants' self-face image over time, followed by a postintervention survey to assess motivation to engage in future sun safety practices. RESULTS: The study sample included 87 participants (median [interquartile (IQR)] age, 14 [11-16] years). Most participants were White (50.6%) and reported skin type that burns a little and tans easily (42.5%). Preintervention sun exposure behaviors among participants revealed that 33 (37.9%) mostly or always used sunscreen on a sunny day, 48 (55.2%) experienced at least one sunburn over the past year, 26 (30.6%) engaged in outdoor sunbathing at least once during the past year, and zero (0%) used indoor tanning beds. Non-skin of color (18 [41.9%], p = .02) and older (24 [41.4%], p = .007) participants more often agreed they felt better with a tan. Most participants agreed the intervention increased their motivation to practice sun-protective behaviors (wear sunscreen, 74 [85.1%]; wear hats, 64 [74.4%]; avoid indoor tanning, 73 [83.9%]; avoid outdoor tanning, 68 [79%]). CONCLUSION: The findings of this cross-sectional study suggest that a photoaging smartphone application may serve as a useful tool to promote sun safety behaviors from a young age.

Diagnostic and Surgical Implications of Non-occlusive Mesenteric Ischemic Ileus Associated With Common Celiacomesenteric Trunk: A Case Report and Literature Review.

The celiacomesenteric trunk (CMT), an exceedingly rare anatomic variant uniting the celiac artery and superior mesenteric artery (SMA), holds significant clinical and surgical implications. Despite its rarity, understanding these implications is crucial for effective management. This report outlines the case of a 99-year-old female presenting with septic shock and abdominal pain, with imaging revealing an incidental CMT. This paper aims to elucidate the surgical implications associated with CMT through a comprehensive case review and literature search. A 99-year-old female with multiple cardiovascular comorbidities presented with altered mental status and right lower quadrant abdominal pain. Upon arrival, the patient exhibited disorientation, an inability to follow commands, hypoxia, and hypotension. Significant laboratory findings included a white count of 20.6 x 109/L, lactate of 6.1 mmol/L, glucose of 53 mg/dL, alanine transaminase (ALT)/aspartate aminotransferase (AST) of 186/336 U/L, and creatinine of 4.2 mg/dL. Immediate interventions involved high-flow oxygen, fluid resuscitation, intravenous antibiotics, and admission to the ICU for septic shock. A CT angiogram (CTA) revealed an incidental large common trunk comprising the celiac trunk and superior mesenteric artery (SMA). There was a high-grade stenosis at the origin of the SMA. However, all the vessels were widely patent distally, and acute mesenteric occlusion was ruled out. By day 12, the patient achieved clinical stability after conservative management and was discharged. Complications such as aneurysm, dissection, stenosis, thrombosis, or acute occlusion of a CMT may necessitate complex surgical interventions, including endovascular procedures or open hepatic surgery. Understanding these technical complexities is vital for avoiding surgical complications in critically ill patients.

A Case of Bullous Sweet's Syndrome Associated With Esophageal Adenocarcinoma.

Sweet's syndrome (SS), or acute febrile neutrophilic dermatosis, characteristically presents with fever, dermal neutrophilic infiltrates, and neutrophilia. It typically manifests as tender erythematous plaques; however, various variants are documented, including bullous. Malignancy-associated Sweet's syndrome (MASS) can present as a paraneoplastic syndrome in those with established cancers or with undiagnosed malignancies. We present a 72-year-old male with a three-day history of a progressive bullous, erythematous papular rash starting on his right forearm and spreading to his extremities, trunk, palms, and soles. It was mildly pruritic but nontender. He had no recent febrile illnesses. On examination, the rash was violaceous with tense bullae overlying edematous targetoid papules coalescing into plaques. Histopathologic analysis of punch biopsies from his abdomen and thigh demonstrated dense inflammatory infiltrates of neutrophils, eosinophils, histiocytes, and lymphocytes, suggestive of neutrophilic dermatosis, or Sweet's syndrome. He was treated with prednisone 1 mg/kg with improvement in his cutaneous symptoms, and a malignancy workup was initiated. Blood work showed elevated free kappa, lambda light chains, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. A positron emission tomography (PET) scan revealed lesions in the esophagus and kidney. He was referred to Heme/Onc, GI, and Urology. He was diagnosed with esophageal adenocarcinoma stage IIb and a renal mass. He has since completed neoadjuvant chemotherapy and radiation, is s/p robotic Ivor-Lewis esophagectomy with no evidence of residual carcinoma on pathology, and is undergoing surveillance with imaging every three months for his renal mass. This case highlights the importance of rapid identification of MASS and the impact dermatologists can make in getting these patients the potentially lifesaving care they need.

Comprehensive Review of Mesothelioma Cases: From Diagnosis to Therapeutic Strategies.

Mesothelioma is a rare and aggressive malignancy typically associated with asbestos exposure. We present the clinical and diagnostic journey of a 63-year-old male carpenter, who presented with concerning symptoms of shortness of breath and total right lung "white-out" on imaging. Comprehensive medical evaluation revealed the presence of malignant pleural mesothelioma. This study underscores the importance of considering mesothelioma as a potential diagnosis in individuals with occupational asbestos exposure and highlights patterns in diagnosing and managing this devastating disease. Early recognition and intervention are essential in improving outcomes for patients diagnosed with mesothelioma.

Peptide-scFv antigen recognition domains effectively confer CAR T cell multiantigen specificity.

The emergence of immune escape is a significant roadblock to developing effective chimeric antigen receptor (CAR) T cell therapies against hematological malignancies, including acute myeloid leukemia (AML). Here, we demonstrate feasibility of targeting two antigens simultaneously by combining a GRP78-specific peptide antigen recognition domain with a CD123-specific scFv to generate a peptide-scFv bispecific antigen recognition domain (78.123). To achieve this, we test linkers with varying length and flexibility and perform immunophenotypic and functional characterization. We demonstrate that bispecific CAR T cells successfully recognize and kill tumor cells that express GRP78, CD123, or both antigens and have improved antitumor activity compared to their monospecific counterparts when both antigens are expressed. Protein structure prediction suggests that linker length and compactness influence the functionality of the generated bispecific CARs. Thus, we present a bispecific CAR design strategy to prevent immune escape in AML that can be extended to other peptide-scFv combinations.

Therapeutic plasma exchange is feasible and tolerable in severely injured patients with trauma-induced coagulopathy.

Objectives: Trauma-induced coagulopathy (TIC) occurs in a subset of severely injured trauma patients. Despite having achieved surgical hemostasis, these individuals can have persistent bleeding, clotting, or both in conjunction with deranged coagulation parameters and typically require transfusion support with plasma, platelets, and/or cryoprecipitate. Due to the multifactorial nature of TIC, targeted interventions usually do not have significant clinical benefits. Therapeutic plasma exchange (TPE) is a non-specific modality of removing and replacing a patient's plasma in a euvolemic manner that can temporarily normalize coagulation parameters and remove deleterious substances, and may be beneficial in such patients with TIC. Methods: In a prospective case series, TPE was performed in severely injured trauma patients diagnosed with TIC and transfusion requirement. These individuals all underwent a series of at least 3 TPE procedures performed once daily with plasma as the exclusive replacement fluid. Demographic, injury, laboratory, TPE, and outcome data were collected and analyzed. Results: In total, 7 patients received 23 TPE procedures. All patients had marked improvements in routine coagulation parameters, platelet counts, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activities, inflammatory markers including interleukin-6 concentrations, and organ system injuries after completion of their TPE treatments. All-cause mortality rates at 1 day, 7 days, and 30 days were 0%, 0%, and 43%, respectively, and all patients for whom TPE was initiated within 24 hours after injury survived to the 30-day timepoint. Surgical, critical care, and apheresis nursing personnel who were surveyed were universally positive about the utilization of TPE in this patient population. These procedures were tolerated well with the most common adverse event being laboratory-diagnosed hypocalcemia. Conclusion: TPE is feasible and tolerable in severely injured trauma patients with TIC. However, many questions remain regarding the application of TPE for these critically ill patients including identification of the optimal injured population, ideal time of treatment initiation, appropriate treatment intensity, and concurrent use of adjunctive treatments. Level of evidence: Level V.