Centro Hospitalar de Lisboa Ocidental

Hepatitis A virus (HAV) infection is usually self-limited and does not progress to chronic liver disease. However, atypical courses such as prolonged cholestatic hepatitis may occur in adults, posing diagnostic and therapeutic challenges.We report the case of a 55-year-old man with hypertension, obesity, and known hepatic steatosis who presented with jaundice, choluria, acholic stools, fatigue, epigastric pain, and nausea. Laboratory evaluation revealed a mixed hepatocellular-cholestatic pattern with predominantly direct hyperbilirubinemia. Acute HAV infection was confirmed (anti-HAV IgM positive), and alternative causes were excluded. Imaging showed no biliary obstruction. Epstein-Barr virus (EBV) serology obtained during the first admission was consistent with past infection (viral capsid antigen (VCA) IgG positive, VCA IgM negative, and EBV nuclear antigen-1 (EBNA-1) IgG positive). The patient improved with supportive care and was discharged after one week.He was readmitted one week later with clinical relapse and severe hyperbilirubinemia (total bilirubin 25.3 mg/dL). Given a household contact with a mononucleosis-like illness, repeat EBV serology showed weak/low-level VCA IgM reactivity (12.1 UA/mL) with persistent VCA IgG positivity. However, subsequent reassessment results returned to VCA IgM negativity with persistent VCA IgG and EBNA-1 IgG positivity, supporting remote EBV infection and suggesting non-specific IgM reactivity (or, less likely, reactivation) rather than primary acute EBV infection. EBV DNA PCR was not pursued due to low clinical and serologic suspicion of active infection and the subsequent resolving course. A genetic study requested during the first admission revealed HFE H63D heterozygosity, with a ferritin level >11,000 ng/mL and transferrin saturation of >80%. The patient improved with ursodeoxycholic acid (UDCA) and individualized iron management. Corticosteroids were not used, given progressive improvement with supportive care and UDCA. Follow-up quantitative liver MRI showed only mild iron overload (43 µmol/g), supporting an acute-phase/inflammatory iron contribution during severe hepatitis, and FibroScan® revealed mild fibrosis (5.3 kPa). This case highlights the importance of stepwise reassessment in prolonged cholestatic HAV, the pitfalls of interpreting transient EBV VCA IgM reactivity in a patient with serology consistent with prior EBV infection, and careful interpretation of marked hyperferritinemia in HFE H63D heterozygotes.

Calf injuries are common, and they are often described in the gastrocnemius, soleus, or plantaris muscle. They are also documented in the flexor hallucis longus and the tibialis posterior, although less frequently. We present a case of an acute flexor digitorum longus muscle strain, a rare injury, often underreported and not well-documented in the literature. We describe the case of a 34-year-old active female undergoing rehabilitation for an incomplete tetraplegia, with suspected multiple sclerosis and left limb monoparesis. She sustained acute pain in her right leg during eccentric plantar flexion movement. Examination revealed pain with flexion of the second to fifth toes. High-resolution ultrasound confirmed disruption of flexor digitorum longus muscle fibers. The patient underwent conservative rehabilitation and returned to her pre-injury activity level within eight weeks, although subclinical strength deficits in the right limb were evident in the gait analysis. Flexor digitorum longus strains are rare but exist and should be considered in the differential diagnosis of calf muscle injuries in healthy and disabled patients. Baseline neurological deficits can influence presentation and rehabilitation progression. Further research is needed to clarify prognosis and return-to-activity criteria forflexor digitorum longus strains.

Antimicrobial resistance has emerged as a critical global health challenge. Significant variability in antibiotic prescribing practices underscores the urgent need for high-quality evidence to inform optimal antibiotic prescribing policies. The ideal duration of antimicrobial therapy remains uncertain, and a one-size-fits-all approach is far from ideal. In this review, we examine bacterial growth kinetics and antibiotic pharmacodynamics and explore various strategies for determining the duration of antibiotic therapy: fixed duration, biomarker-guided, clinical course–based, and the more recent double-trigger approach.

BackgroundUmbilical cord blood (UCB) is a valuable source of hematopoietic stem and progenitor cells (HSPC) for transplantation. However, limited cell numbers require ex vivo expansion for effective treatment of adult patients. Mesenchymal stromal cell (MSC)-based co-cultures offer a supportive environment for HSPC expansion and a model to study niche interactions. Human platelet lysate (hPL) provides a xeno-free alternative to fetal bovine serum (FBS) for MSC culture, but its effect on MSC hematopoietic support remains unclear. This study investigates transcriptomic and functional changes induced by hPL-based culture and their impact on HSPC regulation.MethodsMSC from three bone marrow donors were expanded using hPL- or FBS-supplemented media under three regimens: continuously in cell isolation medium (Direct), adapted from the isolation medium to the other formulation (Adapted), or re-adapted back to the isolation medium (Re-adapted). Co-cultures with UCB-derived CD34+ HSPC assessed functional support over a 7-day period. Bulk transcriptomic profiling (RNA-seq) was performed on MSC under each condition. Differential gene expression and pathway enrichment (GO, KEGG) analysis characterized molecular differences and impacted signaling networks.ResultsMSC properties were reversibly affected by the culture medium. Comparison of hPL-MSC and FBS-MSC revealed 13% differentially expressed genes (DEG), predominantly involved in extracellular matrix organization, chemokine signaling, and cell-cell communication. Minimal transcriptomic variation (1–2% DEG) was observed between Direct and Adapted/Re-adapted MSC. Co-culture with hPL-MSC resulted in significantly lower CD34+ cell expansion (2.4-fold reduction vs. FBS-MSC), though both outperformed the no feeder layer control. While proliferation was reduced, hPL-MSC promoted greater enrichment of primitive subsets, with increased CD34+CD45RA− and CD34+CD45RA−CD90+ populations. Clonogenic potential remained comparable across all conditions. Network analysis identified dysregulation in TGF-β, PI3K-Akt, Notch, Wnt, and JAK/STAT pathways. hPL-MSC showed elevated expression of inhibitory and reduced expression of stimulatory hematopoietic regulatory factors.ConclusionsMSC cultured in hPL- or FBS-supplemented media display significant and reversible transcriptomic differences impacting HSPC expansion. Medium adaptation rapidly reprograms MSC phenotype and gene expression, highlighting responsiveness to environmental cues. Differential expression of key hematopoietic regulatory genes supports the observed functional disparities. These results provide a mechanistic basis for MSC-mediated HSPC support and lay groundwork for optimizing xeno-free expansion systems for clinical application.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04835-z.

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