Moritz Muschaweck

Background: Lead poisoning remains a major environmental health risk for children, as no safe blood lead concentration has been identified and even low-level exposure can cause neurocognitive, behavioral, cardiovascular and renal impairments. Although blood lead levels have declined substantially in high-income countries due to regulatory measures such as the elimination of leaded gasoline and stricter environmental controls, lead exposure continues to pose a significant global public health burden, particularly in low- and middle-income countries. Moreover, uncommon exposure pathways still occur in industrialized nations, making the diagnosis challenging and underscoring the importance of considering environmental exposures in pediatric practice. Case presentation: A 10-year-old boy presented with a two month history of colicky abdominal pain, constipation, postprandial vomiting, 7 kg weight loss, and general weakness. A diagnostic laparoscopy performed at an external hospital was unremarkable. He had undergone appendectomy two years earlier and had no prior health issues. During hospitalization he developed visual disturbances, headaches, and abdominal pain crises requiring opioid treatment. He exhibited psychotic behavior, but no evidence for somatization disorder was found. Results: Laboratory tests revealed mildly elevated aminotransferases, hypochromic microcytic anemia and basophilic stippling on the blood smear. Abdominal x-ray and MRI were unremarkable. Urinary porphyria analysis confirmed elevated porphobilinogen (PBG) and delta-aminolaevulinic-acid (ALA), suggestive of ALA-dehydratase-deficiency (Doss-porphyria). Cranial MRI showed lesions compatible with posterior reversible encephalopathy syndrome (PRES), consistent with previously described porphyria-induced PRES. As differential diagnosis, lead intoxication was considered, as it inhibits ALA-dehydratase and raises ALA more than PBG. Surprisingly, blood lead levels were markedly elevated (581 µg/L ( ≤ 22 µg/L)). Chelation therapy with dimercaptopropanesulfonic acid was initiated, leading in symptom resolution within 48 h. As no source of lead exposure was initially identified and family members showed no elevated levels, ongoing exposure was suspected. After seven weeks, the boy's grandmother discovered the source: a damaged lead tape used as curtain weight, which the boy had been licking for months while gaming. Following removal of this tape, blood lead levels gradually declined. Conclusion: Lead intoxication should remain a differential diagnosis despite its decreasing incidence. Its clinical presentation can mimic porphyria, and lead-induced encephalopathy may resemble PRES.

Background: Enhanced expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on high endothelial venules facilitates lymphocyte migration to sites of intestinal inflammation in inflammatory bowel disease (IBD). This process may be accompanied by increased shedding of soluble MAdCAM-1 (sMAdCAM-1) from endothelial cells. Hence, circulating sMAdCAM-1 may serve as a biomarker of intestinal inflammation in IBD. Results: This single-center study enrolled pediatric ( n = 32) and adult ( n = 73) patients with IBD, as well as healthy controls ( n = 56). Serum samples were collected from all participants, and sMAdCAM-1 concentrations were quantified using an ELISA assay. In healthy individuals, sMAdCAM-1 levels were highest in early childhood, declined during adolescence, and were lowest in adulthood. Concentrations of sMAdCAM-1 did not correlate with gut inflammation in pediatric or adult patients with Crohn’s disease (CD). In contrast, significantly increased sMAdCAM-1 levels were observed in adults with severe ulcerative colitis (UC). Moreover, sMAdCAM-1 levels distinguished healthy children from pediatric UC patients. Conclusions: These findings provide new insights into sMAdCAM-1 as a marker of gut homeostasis and inflammation. Shedding of sMAdCAM-1 decreases during adolescence, and circulating sMAdCAM-1 levels could serve as a biomarker for ulcerative colitis in both pediatric and adult patients, particularly in severe disease.

Introduction: This study intended to explore the existence of a temporal association of changes of sleep stage and gastroesophageal reflux (GER) in infants. Materials and Methods: Documentation of sleep stage and GER was conducted via the use of synchronized polygraphic recording combined with impedance-pH-metry in 15 infants. The total recording-time (Rt) was divided into GER-“window-time” (five seconds before and after the onset of a GER episode), “remaining GER time”, and “GER-free time”, and analyzed for changes of sleep stage. Results: a total of 462 GER episodes were identified during Rt (151.1 h) in all infants. During 1.3 h of window-time; 61 changes of sleep stage (47/h); during 5.9 h of Remaining GER-time, 139 changes of sleep stage (24/h); and during 143.9 h of GER-free time, 4087 changes of sleep stage (28/h) were documented. Change of sleep stage was strongly associated with the onset of GER (p < 0.02 and p < 0.05, respectively). Conclusions: There is a strong temporal association between sleep irregularities, i.e., changes of sleep and episodes of GER in infants. When dealing with disturbed sleep in infants, GER should be considered by caregivers.

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a growing global health problem. NAFLD progression involves a complex interplay of imbalanced inflammatory cell populations and inflammatory signals such as reactive oxygen species and cytokines. These signals can derive from the liver itself but also from adipose tissue or be mediated via changes in the gut microbiome. We analyzed the effects of a simultaneous migration blockade caused by L-selectin-deficiency and an enhancement of the anti-oxidative stress response triggered by hepatocytic Kelch-like ECH-associated protein 1 (Keap1) deletion on NAFLD progression. (2) Methods: L-selectin-deficient mice (Lsel^−/−Keap1^flx/flx) and littermates with selective hepatic Keap1 deletion (Lsel^−/−Keap1^Δhepa) were compared in a 24-week Western-style diet (WD) model. (3) Results: Lsel^−/−Keap1^Δhepa mice exhibited increased expression of erythroid 2-related factor 2 (Nrf2) target genes in the liver, decreased body weight, reduced epidydimal white adipose tissue with decreased immune cell frequencies, and improved glucose response when compared to their Lsel^−/−Keap1^flx/flx littermates. Although WD feeding caused drastic changes in fecal microbiota profiles with decreased microbial diversity, no genotype-dependent shifts were observed. (4) Conclusions: Upregulation of the anti-oxidative stress response improves metabolic changes in L-selectin-deficient mice but does not prevent NAFLD progression and shifts in the gut microbiota.