Variability in COVID-19 Symptom Presentation During Pregnancy and its Impact on Maternal and Infant Outcomes Across the Pandemic.

BACKGROUND: With the dominance of different SARS-CoV-2 variants, the severity of COVID-19 has evolved. We aimed to investigate the difference in symptom prevalence and the association between symptoms and adverse pregnancy outcomes during the dominance of Wild-type/Alpha, Delta, and Omicron. METHODS: COVID-19 related symptom prevalence, maternal and specific neonatal outcomes of 5431 pregnant women registered in this prospective study were compared considering the dominant virus variant. Logistic regression models analyzed the association between specific symptoms and intensive care unit (ICU) admission or preterm birth. RESULTS: Infection with the Delta variant led to an increase in the symptom burden compared to the Wild-type/Alpha variant and the highest risk for respiratory tract symptoms, feeling of sickness, headache, and dizziness/drowsiness. An infection with the Omicron variant was associated with the lowest risk of dyspnea and changes in smell/taste but the highest risk for nasal obstruction, expectoration, headaches, myalgia, and fatigue compared to the Wild-type/Alpha and Delta variant dominant periods. With the progression of the Wild-type/Alpha to the Delta variant neonatal outcomes worsened. Dyspnea and fever were strong predictors for maternal ICU admission and preterm birth independent of vaccination status or trimester of infection onset. CONCLUSION: The symptom burden increased during the Delta period and was associated with worse pregnancy outcomes than in the Wild-type/Alpha area. During the Omicron dominance there still was a high prevalence of less severe symptoms. Dyspnea and fever can predict a severe maternal illness.

Increased TGF-ß: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Survivors of severe congenital diaphragmatic hernia (CDH) present significant respiratory morbidity despite lung growth induced by fetal tracheal occlusion (TO). We hypothesized that the underlying mechanisms would involve changes in lung extracellular matrix and dysregulated transforming growth factor (TGF)-ß pathway, a key player in lung development and repair. Pulmonary expression of TGF-ß signaling components, downstream effectors, and extracellular matrix targets were evaluated in CDH neonates who died between birth and the first few weeks of life after prenatal conservative management or TO, and in rabbit pups that were prenatally randomized for surgical CDH and TO vs. sham operation. Before tissue harvesting, lung tissue mechanics in rabbits was measured using the constant-phase model during the first 30 min of life. Human CDH and control fetal lungs were also collected from midterm onwards. Human and experimental CDH did not affect TGF-ß/Smad2/3 expression and activity. In human and rabbit CDH lungs, TO upregulated TGF-ß transcripts. Analysis of downstream pathways indicated increased Rho-associated kinases to the detriment of Smad2/3 activation. After TO, subtle accumulation of collagen and α-smooth muscle actin within alveolar walls was detected in rabbit pups and human CDH lungs with short-term mechanical ventilation. Despite TO-induced lung growth, mediocre lung tissue mechanics in the rabbit model was associated with increased transcription of extracellular matrix components. These results suggest that prenatal TO increases TGF-ß/Rho kinase pathway, myofibroblast differentiation, and matrix deposition in neonatal rabbit and human CDH lungs. Whether this might influence postnatal development of sustainably ventilated lungs remains to be determined.

The risk of non-sentinel metastases in primary breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) has been established as standard of surgical care in primary breast cancer. If the sentinel node (SN) is negative, axillary dissection (ALND) is not necessary, but if the SN is positive ALND is warranted. This analysis evaluated associated risk factors for non-sentinel metastases in the case of a positive SN. PATIENTS AND METHODS: A retrospective analysis of all SNB performed between 10/1999 and 07/2005 was carried out. RESULTS: A total of 406 patients were included: 214 patients (51%) had SNB with ALND while 197 patients (49%) had SNB only. In 41 of 109 nodal-positive patients, the SN was the only nodal metastasis. In the multivariate analysis, the number of positive SN and the presence of lymphatic vessel infiltration were significant risk factors for additional non-sentinel metastases (p = 0.05 and 0.047, respectively). The risk for non-sentinel metastases was 25.9% without and 59.2% with these risk factors, respectively. CONCLUSION: If the SN is positive, ALND remains obligatory.