Category: 8. Health

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Results

Identification of the Index Patient

The index patient’s illness began on December 13, 2024. Signs and symptoms included, fever, abdominal pain, myalgias, and conjunctivitis, which lasted approximately 1 week and resulted in two health care visits (December 16 and 17). The first visit was to a local emergency department on December 16, where testing for influenza, respiratory syncytial virus, and COVID-19 was performed on a nasopharyngeal specimen. That day, an influenza A–positive rRT-PCR result was received, and the specimen was subsequently sent to SFDPH PHL for further testing as a part of enhanced surveillance. On January 9, 2025, the original specimen tested positive for A(H5) (cycle threshold [Ct] value approximately 29, with Ct values <38 considered positive) using the CDC assay at SFDPH PHL and was confirmed by CDC using the same A(H5) primer and probe set on January 14. A second specimen (oropharyngeal) collected by SFDPH on January 10 (25 days after the first specimen, when the child had been asymptomatic for 21 days), was positive for A(H5) (Ct value approximately 37); specimens collected 4 days later were negative.

Sequencing revealed clade 2.3.4.4b, genotype B3.13 viruses, closely related to B3.13 viruses detected in humans and animals in California (Figure 1). Phylogenetic analyses revealed that the sequences clustered together on an independent branch relative to other California human and dairy cattle sequences. Nucleotide and amino acid changes in the hemagglutinin (HA) and nucleoprotein (NP) genes were observed between the two sequences, consistent with viral replication, and no critical markers of mammalian adaptation (increased virulence or transmission risk) were identified.

Index Case Investigation

The index patient lived in an urban environment, did not travel, and had no reported exposure to dairy cows, cats, poultry, birds or other wild animals in the 10 days prior to the illness onset; the family had a pet dog. There were no animals at school, and the patient’s family did not work in occupations that increase risk for A(H5N1) virus infection (handling, slaughtering, defeathering, butchering, culling, caring for, or milking infected animals). A member of the patient’s family purchased raw poultry at a live bird market 2 weeks before the child’s illness onset; the poultry was cooked and consumed the same day it was purchased.

Investigation of Close Contacts

Among 84 persons identified as possible contacts of the index patient (seven household, 53 school, and 24 health care), 67 (80%) met the close contact definition (Figure 2). No household contacts reported illness. School absences were reported for 34 (64.2%) school contacts, 26 (76.5%) of whom were interviewed (one teacher and parents of 25 children). All interviewed parents reported respiratory illnesses in their children, including seven who were symptomatic at the time of interview. The teacher had had influenza-compatible symptoms but was asymptomatic at the time of interview. Four persons were tested for one or more respiratory viruses (COVID-19, RSV, or influenza) previously while ill; all test results for influenza were negative. Among the 24 health care worker contacts from three facility visits (two urgent care, one emergency department), 11 (45.8%) completed a survey, including seven who had close contact with the patient; none reported influenza-compatible symptoms. All 11 available respiratory (oropharyngeal and nasal) specimens from close contacts (seven household and four school) were A(H5)-negative by rRT-PCR.

Serum specimens were collected from the index patient (32 days from onset to convalescent serum collection), three adult household contacts, two school contacts, and four health care contacts. Among these nine contacts, the median interval between their first exposure to the index patient and serum collection was 45 days (range = 9–47 days), and the median interval between their last exposure and serum collection was 26 days (range = 0–46 days). The patient had antibodies to all three wild-type A(H5N1) viruses, with elevated antibody titers in all assays, consistent with recent H5N1 infection: A/Texas/37/2024 (B3.13) (MN titer = 160, HI titer = 320); A/Michigan/90/2024 (B3.13) (MN titer = 320, HI titer = 226); and A/Washington/240/2024 (D1.1) (MN titer = 113, HI titer = 320). All nine close contacts’ serology results were negative for all three wild-type A(H5N1) viruses.

With so much confusion around what makes a grain food truly healthy, new research now offers a clearer picture: a combination of grain foods can support better nutrition and metabolic health when they deliver on nutrient density. A new study published in Nutrients, which analyzed the diets of more than 14,000 Americans over five years, found that both whole and refined grain foods play a role in improved diet quality, nutrient intake and everyday accessibility.

Conducted by researchers at the Center for Public Health Nutrition at the University of Washington, the peer-reviewed study analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2023. The analysis found that many everyday grain foods – including some breads, cereals and tortillas – ranked surprisingly high for nutrient density and affordability. The findings offer a more nuanced view of grain foods, moving beyond assumptions and highlighting a broader range of options that can support health.

Using two new nutrient profiling models to evaluate carbohydrate quality and overall nutrient density, the Carbohydrate Food Quality Score CFQS-3 and the Nutrient Rich Food (NRF9.3) index, the study identified which grain foods qualify as “healthy grain foods” based on higher levels of fiber, protein and essential nutrients, and lower amounts of added sugars, saturated fat and sodium. This approach revealed that both whole and refined grain foods can meet the mark, contributing meaningfully to diet quality and health. People who consumed more of these healthy grain foods had better overall nutrient intake, healthier eating patterns and more favorable markers of metabolic health.

Key findings include:

• Improved diet quality and nutrient intake. People who consumed more healthy grain foods had better overall diet quality and higher intakes of fiber, protein, iron, calcium, potassium and magnesium.
• Includes both whole and refined grain foods. Both types scored highly for nutrient density, with many refined or enriched options – like certain breads, cereals and tortillas – delivering strong nutritional value alongside whole grain choices.
• Part of healthier overall eating patterns. People who ate the most healthy grain foods also consumed more fruits, vegetables and lean proteins, suggesting these grain foods may support or reflect broader healthy habits.
• Linked to better metabolic health. Adults with higher intakes of these grain foods were less likely to be obese and had lower fasting insulin levels, a key marker of metabolic function.
• No added cost. Healthy grain foods were no more expensive than less healthy options and were often more affordable per gram or calorie.

“Healthy grains are a critical component of healthy diets” said Dr. Adam Drewnowski, Professor of Epidemiology at the University of Washington. “Our evaluation took whole grain content into account, along with fiber, vitamins and minerals. By delivering key nutrients such as fiber, iron, B vitamins and folate, grain foods can make a meaningful contribution to healthier eating patterns among all population groups.”

As nutrition guidance continues to evolve, this study adds important clarity around the role of grain foods in supporting public health. The findings highlight the value of balance – not just in overall eating patterns, but in the types of grain foods we include. Recognizing the nutritional contributions of both whole and refined/enriched options offers a more inclusive and realistic path to better outcomes for Americans’ diet and overall health. To learn more, visit GrainFoodsFoundation.org.

This study was supported through an unrestricted grant from the Grain Foods Foundation (GFF), a nonprofit organization dedicated to nutrition science and education to better understand the role of grain foods in healthful diets. GFF had no influence over the study design, data analysis or interpretation of findings.

A major study has investigated the relationship between walking and the risk of developing chronic lower back problems. The findings could save the healthcare system significant amounts of money while also alleviating many people’s back pain – if we just follow the simple advice provided.

The results are clear: People who walk a lot have less back pain than people who do not walk much – and the volume is what matters most, not the intensity.. It is better to walk a lot than to walk fast.

People who walk more than 100 minutes every day have a 23 per cent lower risk of lower back problems than those who walk 78 minutes or less.”

Rayane Haddadj

He is a PhD candidate at the Department of Public Health and Nursing at the Norwegian University of Science and Technology (NTNU), and is part of a research group that specifically studies musculoskeletal disorders.

The results of the new study were published in the JAMA Network Open journal. The article has already received a lot of attention.

Even leisurely strolls are beneficial

It probably comes as no surprise that physical activity is good for your back, but until now we have not actually known whether the amount of low-intensity walking we do also helps.

“Intensity also plays a role in the risk of long-term back problems, but not as much as the daily amount of walking,” emphasized Haddadj.

A total of 11,194 people participated in the study, which is part of the Trøndelag Health Study (The HUNT Study). What makes this study unique is that the volume and intensity of daily walking were measured using two sensors that participants wore on their thigh and back for up to a week.

The results may be important in relation to preventing chronic back problems. Until now, there has been little research on the prevention of these types of musculoskeletal problems. It is well known that physical activity can prevent a wide range of illnesses and ailments. This study is important because it confirms that physical activity, and especially daily walking, can help prevent long-term lower back problems.

Back pain is a very common ailment

“The findings highlight the importance of finding time to be physically active – to prevent both chronic back problems and a number of other diseases. Over time, this could lead to major savings for society,” said Paul Jarle Mork, a professor at NTNU’s Department of Public Health and Nursing.

Back and neck problems cost society several billion kroner every year. Musculoskeletal disorders are likely the largest expense within the Norwegian healthcare system.

Back pain is one of the most common health problems in Norway. Depending on what you include, between 60 and 80 per cent of us will experience back problems at some point in our lives. At any given time, around one in five Norwegians has back trouble.

The causes are many and complex, but the solution might be as simple as putting on your shoes and going for a walk – each and every day.

Introduction

Mucormycosis is one of the most common causes of deep fungal infections, alongside candidiasis and aspergillosis.¹ It is an invasive fungal infection caused by ubiquitous filamentous fungi belonging to the order Mucorales and is characterized by an extremely high mortality rate. In recent years, the reported incidence of mucormycosis has risen, probably due to the growing population of high-risk individuals and advances in diagnostic techniques.² The risk factors for this disease include cirrhosis, neutropenia, prolonged corticosteroid use, malnutrition, poorly controlled diabetes, iron overload, hematologic malignancies, recent allogeneic stem cell or solid organ transplantation, severe burns, and major traumatic injuries. High-risk patients may develop mucormycosis following exposure to spores via inhalation or traumatic inoculation, as these spores are widespread in the environment, leading to either community-acquired or nosocomial infections.^3,4 Clinically, mucormycosis, like aspergillosis, exhibits angioinvasive growth, predisposing patients to thrombosis and emboli.⁵ It is marked by extensive necrotic vasculitis that results in thrombus formation, progressive tissue infarction, and even systemic dissemination.⁶ Its management typically requires aggressive surgical debridement and prolonged antifungal therapy.⁷ Infective endocarditis (IE) demonstrates significant clinical burden, with 2019 incidence reported at 13.8 per 100,000 and overall mortality persisting at 30%.⁸ The condition is predominantly caused by Staphylococcus aureus, streptococci (notably viridans group), and enterococci—collectively accounting for ~80% of cases. Major risk factors include underlying cardiac abnormalities (eg, rheumatic or congenital heart disease), prosthetic valves, intracardiac devices, and intravenous drug use. In contrast, fungal endocarditis comprises a distinct minority (1–3% of IE cases) yet carries disproportionate mortality exceeding 70%, with Candida species responsible for >50% of these infections and Aspergillus being less common.^9,10 Notably, key risk factors specific to this fulminant subtype include prosthetic valves, prior cardiac surgery, and immunosuppression.¹⁰ Mucormycotic endocarditis is a scarcely reported disease with near-complete lethality.⁶ Given the high mortality rate of mucormycosis, it is important to improve its detection rate through better diagnostic strategies and timely treatment and management. Gaining a clearer picture of the clinical manifestations, diagnostics, and management would help improve its diagnosis and management and potentially help improve its survival rate. This report describes the clinical manifestations and course of mucormycosis in a post-liver transplantation adult patient and reviews the existing literature on mucormycotic endocarditis.

Case Presentation

A 51-year-old male (weight: 93 kg, height: 170 cm, BMI: 32.2 kg/m²) underwent liver transplantation at our hospital for acute-on-chronic liver failure. His medical history included hypertension, diabetes mellitus, and hepatitis B surface antigen positivity for over a decade. One month prior to surgery, he developed jaundice (scleral icterus and skin yellowing), abdominal distension, fatigue, decreased appetite, and dark tea-colored urine, with progressive worsening. Initial laboratory tests at a local county hospital revealed that his total bilirubin level was 338 μmol/L; direct bilirubin, 268.7 μmol/L; indirect bilirubin, 69.7 μmol/L; HBV-DNA, 10⁹ IU/mL; international normalized ratio, 2.32, and prothrombin time, 24.6 s. The patient received hepatoprotective therapy with glycyrrhizin-based medications (80 mg IV daily) and intravenous S-adenosylmethionine (1,000 mg/day), but his condition deteriorated despite this. Twelve days before the transplant procedure, he was transferred to our hospital. Chest CT showed no infiltrates, and the findings of electrocardiography and echocardiography were unremarkable. Treatment included tenofovir alafenamide (antiviral), hepatoprotective agents, choleretics, gastric protectants, laxatives, and ammonia-lowering therapy. During hospitalization, oliguria (25 mL/h) and increasing lactate levels (12 mmol/L) prompted admission to the intensive care unit 8 days before the procedure for continuous renal replacement therapy. The lactate levels improved temporarily, but hypotension and hypoxemia necessitated mechanical ventilation the next day. Blood cultures revealed the presence of Gram-negative bacilli, and chest radiography revealed bilateral pulmonary infiltrates. The patient was diagnosed with septic shock complicated by pulmonary infection. Following ICU admission, empiric therapy with meropenem (1 g every 8 hours) and micafungin (100 mg/day) was immediately initiated and maintained until liver transplantation. Vancomycin (500 mg every 8 hours) was additionally administered starting 4 days prior to the procedure. Serial monitoring demonstrated progressive normalization of serum lactate levels, resolution of shock, and reduction of inflammatory biomarkers (C-reactive protein and procalcitonin) to near-normal ranges. Preoperative arterial blood gas analysis indicated a PaO₂/FiO₂ ratio of 204 mmHg.

Liver transplantation was performed with a graft from a 48-year-old male brain death donor who died of hypertensive intracerebral hemorrhage. The procedure, a modified piggyback technique, lasted 7 h and 5 min, with a cold ischemia time of 3 h and 33 min and an anhepatic phase of 50 min. Intraoperative immunosuppression therapy included methylprednisolone (1000 mg) and basiliximab (20 mg). Tacrolimus (target trough: 3–5 ng/mL) was initiated on postoperative day (POD) 3. Preoperative serum metagenomic next-generation sequencing (mNGS) preliminarily detected mucormycetes, prompting immediate treatment with isavuconazole (200 mg IV) before entering the operating room. The diagnosis of mucormycosis was established based on the patient’s history of suboptimal long-term glycemic control in diabetes mellitus, underlying chronic liver disease with progression to hepatic failure, and definitive evidence from serum mNGS testing.

Bradycardia (40–50 bpm) and hypotension occurred on POD 1, with the electrocardiogram showing high-grade atrioventricular block (Figure 1A). A temporary VVI pacemaker was implanted (Figure 1B). Formal serum mNGS results confirmed the presence of Rhizomucor pusillus (203 sequence reads) and Cunninghamella elegans (40 sequence reads). Necrotic eschar-like skin lesions were noted on the upper abdomen (Figure 2). Isavuconazole (200 mg/day after a 48-h loading dose of 200 mg/8 h) and amphotericin B colloidal dispersion were administered (2–4 mg/kg of body weight/day). The initial postoperative antimicrobial regimen comprised meropenem for Gram-negative coverage and vancomycin for Gram-positive coverage. On POD 7, antimicrobial therapy was de-escalated to cefoperazone-sulbactam based on sputum culture identification of Ralstonia mannitolilytica with susceptibility testing (MIC ≤4μg/mL). Subsequently, on POD 10, therapy was shifted to levofloxacin due to coagulopathy evidenced by elevated INR. Postoperative echocardiography was performed every other day, and serum troponin (TnI) and B-type natriuretic peptide (BNP) levels were monitored daily. Progressive elevation of TnI and BNP levels was observed (Figure 3). On POD 4, non-contrast CT scans of the head and chest, along with abdominal CT angiography, were performed. The scans revealed large areas of pulmonary exudates in the lungs and multiple wedge-shaped infarcts in the spleen and kidneys (Figure 4). Intravenous immunoglobulin (0.25 mg/kg of body weight/day) was administered to enhance humoral immunity.

Figure 1 Postoperative electrocardiogram findings. (A) High-grade atrioventricular block with 3:1 atrioventricular conduction and complete left bundle branch block. (B) Post pacemaker implantation ECG showing VVI pacing mode with a pacing rate of 90 beats per minute (bpm). The black triangles indicate the pacing spikes.

Figure 2 Clinical manifestations of skin necrosis at different stages of progression. (A) Circular erythema; (B) Swelling/necrosis; (C) Dry ulcer; (D) Necrotic eschar.

Figure 3 Post-transplantation daily trends in serum troponin, B-type natriuretic peptide, and total bilirubin levels. Postoperative monitoring demonstrated serum total bilirubin levels fluctuating around 200 μmol/L, while serum troponin I and B-type natriuretic peptide (BNP) exhibited progressively increasing trends.

Figure 4 Multiorgan CT findings showing disseminated mucormycosis. (A) Chest CT demonstrating multifocal consolidations in the lungs. (B) Splenic wedge-shaped infarct following vascular distribution (arrowhead). (C and D) Bilateral renal multiple wedge-shaped infarcts aligned with vascular territories (arrowhead).

On POD 7, echocardiography revealed apical wall motion abnormalities, which were accompanied by increased levels of TnI (23.8 ng/mL) and BNP (1439.5 pg/mL). Repeated serum mNGS detected Cunninghamella bertholletiae (841 sequence reads). Further, expansion of the cutaneous lesions was observed (Figure 2), and bedside biopsy of the abdominal eschar was performed. Coronary angiography showed 30% stenosis in the proximal left anterior descending artery (for which no intervention was administered).

Refractory shock and escalating lactate levels on POD 8 necessitated maximal vasopressor support (with norepinephrine). Repeated serum mNGS confirmed persistence of R. pusillus (52 sequence reads). Echocardiography demonstrated ventricular septal fistula (into the right atrium) and mitral valve perforation on POD 10 (Figure 5). The patient died of progressive hemodynamic collapse on POD 11. Postmortem skin biopsy pathological examination confirmed broad, non-septate hyphae consistent with mucormycosis in the deep dermis and subcutaneous fat layers (Figure 6).

Figure 5 Echocardiographic findings on postoperative day 7. (A) Sac-like structure protruding into the left atrium from the base of the anterior mitral leaflet, measuring 1.0×1.0 cm (arrowhead). (B) Echo discontinuity in the membranous ventricular septum with a sac-like structure extending into the right atrium (1.4 × 0.4 cm) (arrowhead). (C) Perforation of the membranous ventricular septum with a defect width of 0.65 cm (arrowhead). (D) Peak flow velocity of 4.1 m/s at the septal perforation site.

Figure 6 Biopsy pathology images of eschar necrosis in the abdominal wall skin. (A) Hematoxylin and eosin staining, (B) periodic acid-Schiff staining, (C) Grocott’s methenamine silver (GMS) staining, and (D) immunofluorescence staining demonstrating abundant broad, non-septate, right-angled branching hyphae (arrowhead).

Discussion

The present report describes a rare case of post-liver transplantation mucormycosis in a patient characterized by persistence of Cunninghamella and Rhizomucor species, cardiac involvement, progressively worsening necrotic lesions and eschar formation, and systemic spread, all of which contributed to a poor prognosis that eventually led to death on the 11^th day after the procedure. The observations here highlight the importance of employing molecular diagnostic technologies such as mNGS for accurate detection and early initiation of antifungal treatment.

Mucormycosis is most commonly caused by Rhizopus, Mucor, and Lichtheimia (formerly Absidia) species.¹¹ While Cunninghamella (formerly classified under Absidia) is less frequent, it is associated with exceptionally high mortality.¹² In this case, repeated serum mNGS detected Cunninghamella and Rhizomucor, which explains the patient’s poor prognosis. Mucormycosis progresses rapidly and is notoriously challenging to diagnose, contributing to its dismal survival rates.¹³ Serological diagnosis is particularly difficult compared to the diagnosis of other fungal infections, and historically, a definitive diagnosis was often achieved only postmortem via histopathological assessment.^1,14 In the present case, too, the causative pathogen was identified later on in the disease course through mNGS, and the diagnosis was confirmed only through postmortem skin biopsy analysis. These findings highlight the current challenges in the timely diagnosis and treatment of mucormycosis.

The diagnosis of mucormycosis relies on early recognition of host risk factors, clinical signs, imaging observations, histopathological manifestations, and molecular diagnostics.¹⁵ The 2019 ECMM/MSGERC guidelines¹⁶ emphasize the application of imaging, histopathology, and culture for diagnosis, but these methods are limited by low culture yield and delayed histopathological presentation. For example, Mucorales lack 1,3-β-D-glucan in their cell walls,¹¹ as a result of which serum galactomannan and β-D-glucan assays usually yield false-negative results.¹⁷ Further, while histopathological examination often reveals characteristic broad, pauci-septate hyphae, cultures frequently remain negative.¹⁸ Instead, fluorescence microscopy and molecular diagnostic techniques (eg, PCR and mNGS) may offer enhanced diagnostic accuracy,^19,20 as observed in the present case, underscoring the critical role of mNGS in early detection, particularly in high-risk perioperative settings. Additionally, high-resolution CT may show angioinvasive features (eg, nodules, halo/reverse halo signs, cavities, and wedge-shaped infarcts).⁶ Specifically, the reverse halo sign—a focal ground-glass opacity encircled by consolidation—is an early indicator of pulmonary mucormycosis.^21,22 Disseminated disease, often hematogenously seeded from the lungs, may involve the heart, brain, or kidneys.²³ In this patient, CT imaging revealed wedge-shaped hypodense lesions in the kidneys and spleen aligned with vascular distributions, suggestive of Mucorales-related intravascular fungal embolism leading to renal and splenic infarctions. These radiological findings indicated disseminated systemic mucormycosis.

Mucormycosis is classified based on anatomical involvement into rhinocerebral, pulmonary, cutaneous, gastrointestinal, and disseminated forms, as well as rare forms such as endocarditis, osteomyelitis, peritonitis, and renal infections.⁶ Cutaneous mucormycosis typically arises from traumatic inoculation of fungal spores into disrupted skin (eg, surgery, burns, and trauma), potentially leading to systemic dissemination.^24,25 Skin lesions in primary cutaneous mucormycosis include abscesses, necrotic eschars, dry ulcers at the inoculation site. In contrast, diffuse erythema is a nonspecific sign of disseminated disease resulting from hematogenous spread, typically originating from pulmonary or rhinocerebral foci in immunocompromised hosts.^26,27 In the present case, initial circular erythema progressed to necrosis and eschar formation, with lesions expanding in both number and severity. Thus, such cutaneous changes—particularly isolated, round erythematous, or necrotic lesions in post-transplant patients—should raise suspicion of mucormycosis and prompt immediate skin biopsy or mNGS to confirm the diagnosis and initiate aggressive antifungal therapy with or without surgical debridement.²⁰

As reported by F. Lanternier et al²⁸ infection site significantly impacted survival, with mortality rates of 22% (cutaneous), 25% (rhinocerebral), 48% (pulmonary), and 79% (disseminated). Pulmonary mucormycosis, the most common form in solid organ transplant recipients,^29,30 often extends to the chest wall, vasculature, or mediastinum.^31,32 Cardiac involvement (endocarditis or myocarditis) is rare but carries near-universal mortality.⁶ Mucormycotic endocarditis manifests catastrophically as heart failure, valvular perforation, intracardiac masses, or sudden cardiac arrest. Without radical surgical excision and prolonged antifungal therapy, mortality approaches 100%.²⁰ A literature review identified 21 reported cases of cardiac mucormycosis between 1994 and 2023^17,32–51 and found only 4 survivors,^38,39,42,51 one of whom experienced relapse³⁹ (Table 1). The affected patients, including a blood type-incompatible liver transplant recipient, were found across all age groups and were reported to be universally immunocompromised as a result of immunosuppressive drug therapy.⁴⁸ The clinical manifestations of cardiac mucormycosis include intracardiac mass or vegetations, myocardial infarction, congestive heart failure, conduction system disease, valvular incompetence, and pericarditis.⁵² Among the cases identified in the literature review, 2 presented with fatal complete atrioventricular block,^33,45 5 exhibited coronary artery embolism (4 of whom manifested STEMI),^{32,44,46,47,50} 10 demonstrated intracardiac masses or valvular vegetations, and 4 patients displayed myocarditis-associated symptoms.^17,34,35,37 In the present case, an adult patient undergoing liver transplantation with a donation after brain death (DBD) graft for hepatic failure developed postoperative high-grade atrioventricular block and endocarditis complicated by perforation of the membranous ventricular septum and mitral valve. The clinical course culminated in fatal cardiac failure with cardiogenic shock. Diagnosis was predominantly confirmed histologically, often postmortem (50% of cases in our review, as observed in the current case too), highlighting the challenges with early detection and rapid progression. The International Society for Cardiovascular Infectious Diseases (ISCVID) updated infective endocarditis diagnostic criteria to reflect advances in microbiology, diagnostics, epidemiology, and management. The 2023 Duke-ISCVID criteria now include PCR and metagenomic sequencing as major microbiological criteria.⁵³ In the reviewed literature, all 6 patients with confirmed Cunninghamella infection died,^{32,34,43,48,49} as observed in the present case. Moreover, species identification was not possible in 11 cases of Mucorales infection. Cunninghamella infection portends a dismal prognosis, with survival rates below 30%. All previously reported cases of disseminated Cunninghamella disease were fatal.⁵⁴ Disseminated multiorgan involvement was documented in 15 cases, with the origin of the disease identified as pulmonary mucormycosis with cardiac invasion in one case³² and mycotic endocarditis secondary to catheter-related infection in another case.³⁸ Cardiac involvement typically reflects disseminated disease, arising via hematogenous spread or direct pulmonary invasion. Autopsy findings in such cases reveal fungal thrombi, invasive necrosis of the myocardium, and infarction. In this case, high-grade atrioventricular block on POD 1 corresponded to echocardiographic findings of septal perforation near the atrioventricular node and His bundle. Overall, the observations in the present case corroborate the findings of other studies on cases of mucormycosis with cardiac involvement and highlight the challenges with diagnosis.

Table 1 Epidemiological Features, Clinical Presentations, Pathogen Identification, Diagnostic Strategies, and Treatment Protocols in Cardiac Mucormycosis Patients

Management of mucormycosis requires risk stratification, rapid antifungal therapy, surgical debridement, and reversal/elimination of predisposing factors.⁵⁵ First-line agents include lipid-based amphotericin B (5–10 mg/kg of body weight/day), with isavuconazole and posaconazole recommended as preferred options for salvage therapy. Although lipid-based amphotericin B has a lower incidence of nephrotoxicity, its higher cost leads to the more frequent use of conventional amphotericin B in Asian and African countries. The optimal duration of treatment for mucormycosis remains unclear, typically requiring weeks to months, and there is limited high-quality evidence supporting combination antifungal therapy. In our review of mucormycosis with cardiac involvement, all 4 surviving patients^38,39,42,51 received timely antifungal therapy with amphotericin B. In our case, although mucormycosis was detected via serum mNGS and treated with isavuconazole combined with amphotericin B colloidal dispersion, the dosage was suboptimal (3–5 mg/kg of body weight/day). The 2019 ECMM/MSGERC guidelines¹⁶ recommend that surgical intervention be strongly considered when mucormycosis is suspected, provided surgical conditions are feasible. Notably, 3 patients (from our review) who achieved clinical improvement or were cured underwent prompt surgical debridement^38,39,42 (including one case with incomplete initial radical resection that required secondary debridement due to recurrent infection).⁴² However, cardiac manifestations typically emerge when disseminated infection is already established, precluding surgical intervention, which was observed in most patients in the reviewed literature. In the present case, too, the patient rapidly developed high-grade atrioventricular block that was suggestive of fungal invasion of the membranous portion of the interventricular septum. In addition, the patient exhibited clinical manifestations of disseminated infection involving skin, kidneys, spleen, and lungs. These presentations rendered the patient ineligible for surgical intervention. Consequently, the infection remained uncontrolled. Retrospectively, serum mNGS testing should have been performed earlier when the patient was transferred to the ICU in the preoperative period due to shock and respiratory failure, as this would have enabled earlier initiation of therapy and slowed disease progression.

Conclusions

Despite its relative rarity, mucormycosis poses a significant threat to immunocompromised patients due to its persistently high mortality rates. The nonspecific clinical manifestations and signs of mucormycosis present substantial diagnostic and therapeutic challenges. With advancements in liver transplantation techniques and perioperative management, an increasing number of patients with end-stage liver disease are undergoing transplantation, necessitating heightened vigilance for mucormycosis in this population. Direct microscopy, fungal culture, and histopathology remain the cornerstone of diagnosis but face several limitations in terms of timely diagnosis. Instead, novel molecular diagnostic technologies offer a complementary approach to facilitate early detection and prompt initiation of therapy. Effective management of mucormycosis requires multidisciplinary collaboration, and timely administration of targeted antifungal therapy is critical to reducing mortality.

Data Sharing Statement

Data supporting this study can be obtained from the designated corresponding author Wei Zhang at [email protected] upon request. Other co-corresponding authors do not manage data requests.

Ethics Approval

This study complied with the guidelines of the Chinese Ethics Committee and the Declaration of Helsinki and was approved by the Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine. All organs were donated voluntarily with written informed consent, and the donations were conducted in accordance with the Declaration of Istanbul. Since January 1, 2015, organ procurement from executed prisoners had been completely ceased in China, and no organs from executed prisoners were used in any case involved in this study.

Consent for Publication

We confirm that all authors have approved the submission of this manuscript for publication and the consent of the patient’s family was obtained for publication of the data and images. Ethical approval for publication of anonymized case details was granted by the Institutional Review Board of the First Affiliated Hospital, Zhejiang University School of Medicine.

Acknowledgments

We sincerely thank our colleagues at the transplant center for their contribution to this study and their thoughtful comments, which greatly enhanced our work.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This project was supported by the Central Government Guidance Funds for Local Scientific and Technological Development (2024ZY01023).

Disclosure

The authors have no conflicts of interest to declare in this work.

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A new study explains why smokers have a higher chance of developing pancreatic cancer and why they tend to have worse outcomes than nonsmokers.

Researchers from the University of Michigan Health Rogel Cancer Center found a specific cell that responds to environmental toxins such as those found in cigarettes. When the toxins bind to the cells, it leads to release of a protein, interleukin-22, causing tumors to grow aggressively in mice with pancreatic cancer. Digging deeper led the team to identify a super-suppressive type of immune cell that fuels this response while also stopping the immune system from fighting tumor growth.

The study is published in Cancer Discovery, a journal of the American Association for Cancer Research.

Researchers started by giving a chemical found in cigarettes and other environmental toxins to mice that had pancreatic tumors. They were looking to see how that would impact Interleukin-22, or IL22. Previous work showed IL22 plays a role in the pancreatic tumor microenvironment. A specialized receptor found on IL22 producing cells binds to chemicals, not natural proteins in the body, so it was a logical first step to see how the chemical carcinogen would impact IL22.

It dramatically changed the way the tumors behave. They grew much bigger, they metastasized throughout the body. It was really quite dramatic.”

Timothy L. Frankel, M.D., senior study author, co-director of the Rogel and Blondy Center for Pancreatic Cancer and Maud T. Lane Professor of Surgical Oncology at Michigan Medicine

Next, they started digging into what mechanism was leading to this enhanced tumor growth. They confirmed that in mice with no immune system, chemical toxins did not cause tumor growth, suggesting that the carcinogen was functioning within the immune system. From there, they uncovered a role for IL22 producing T-regulatory immune cells, a type of cell that’s been previously implicated in autoimmune disorders but not in pancreatic cancer.

“These T-regulatory cells have the ability to both make IL22 but also massively suppress any anti-tumor immunity. It’s a two-pronged attack. When we eliminated all the Treg cells from these mice, we reversed the entire ability of the cigarette chemical to let the tumor grow,” Frankel said.

They confirmed their results in human immune cells and also in cells from patients with pancreatic cancer. Sure enough, smokers with pancreatic cancer had more Treg cells than nonsmokers.

Researchers were further able to show that an inhibitor that blocks the cigarette chemical was effective at shrinking tumors.

“If we are able to inhibit the super suppressive cells, we might also unlock natural anti-tumor immunity. This could be even further activated by current immunotherapies, which do not work well in pancreatic cancer because of the immunosuppressive environment,” Frankel said.

More research is needed to understand the potential to use a drug that inhibits this environmental toxin or that blocks this signaling pathway. In addition, the study results suggest the need for personalized treatment based on patients’ exposure to cigarette smoke.

“There’s a potential that we need to treat smokers who develop pancreatic cancer differently,” Frankel said. “We may also need to screen smokers more closely for pancreatic cancer development. There is not a great screening mechanism, but people who smoke should be educated about symptoms to look out for and consider referrals to a high-risk clinic.”

Signs of pancreatic cancer include low back pain, yellowing of the skin and unexplained weight loss.

Frankel adds that people with a family history of pancreatic cancer or with other pancreatic inflammatory diseases should avoid smoking.

Additional authors: Brian D. Griffith, Padma Kadiyala, Jake McGue, Lei Sun, Aadith Kuman, Carlos E. Espinoza, Katelyn L. Donahue, Matthew K. Iyer, Cameron Speyer, Sarah Nelson, Andrew Spiteri, Ahmed M. Elhossiny, Kristee Brown, Holly Attebury, Filip Bednar, Eileen S. Carpenter, Ilona Kryczek, Yaqing Zhang, Weiping Zou, Marina Pasca di Magliano

Funding for this work is from National Cancer Institute grants P30CA046592, R01CA268426, R01CA260752, R01CA271510, R01CA264843, U01CA224145, U01CA274154, T32CA00967; National Institutes of Health grant 5R01DK128102; U.S. Department of Veterans Affairs grant 5I01BX005777; Society of University Surgeons Resident Research Award; Fredrick A. Coller Surgical Society Research Award.

Source:

Michigan Medicine – University of Michigan

Journal reference:

Griffith, B. D., et al. (2025) Aryl hydrocarbon receptor ligands drive pancreatic cancer initiation and progression through pro-tumorigenic T cell polarization. Cancer Discovery. doi.org/10.1158/2159-8290.CD-25-0377

Students vape to fit in, and cope with stress

Educators suggested a range of reasons why vaping occurs in middle and high school, including peer pressure, self-soothing, and experimentation. Students are commonly turning to vaping as they try to fit in with peers and assert independence from adults. Educators noted that vaping was common among students struggling with anxiety, stress, and depression.

“I definitely see some middle schoolers that are actually addicted to nicotine now, to the point where they’re trying to sneak it in (school) and they get caught. They get this sort of desperation about them, because they know they’re going to be struggling.” Middle School-Based Psychologist, Minnesota

“These kids are self-medicating. Vaping gives them a dopamine hit, a break from stress, a moment of comfort. It’s everywhere—their parents do it, siblings, friends. But at its core, they’re using it to escape what they’re feeling.” Middle School Assistant Principal, Ohio

“Between that [vapes] and the phones, those two addictions, irritability is a big thing. Not being able to stay focused, needing to get up and go get their fix.” High School-Based Psychologist, California

Researchers have completed the first-ever activity map of a mammalian brain in a groundbreaking duo of studies, and it has rewritten scientists’ understanding of how decisions are made.

The project, involving a dozen labs and data from over 600,000 individual mouse brain cells, covered areas representing over 95% of the brain. Findings from the research, published in two papers in the journal Nature, suggest that decision-making involves far more of the brain than previously thought.