Congenital high airway obstruction syndrome (CHAOS): Natural history,prenatal management strategies,and outcomes at a single comprehensive fetal center

PurposeCongenital high airway obstruction syndrome (CHAOS) is a devastating fetal condition of complete airway discontinuity resulting in significant hydrops and extreme lung hyperplasia. It is universally fatal with survival reported only in the rare spontaneous fistulization or EXIT intervention (Ex Utero Intrapartum Treatment). Even in these cases, mortality remains high, and current investigations are targeting prenatal interventions. This report describes our experience with management and fetal interventions for CHAOS, including laser laryngotomy.MethodsWe retrospectively reviewed all patients diagnosed with CHAOS at a single academic institution between 2006 and 2017.ResultsFifteen patients were identified. Eight had obstruction at the trachea and seven at the larynx. In the laryngeal obstructions, three expired shortly after birth, and one survived after spontaneous fistulization and subsequent EXIT to tracheostomy. The remaining three underwent in-utero treatment with laser laryngotomy. One had preterm premature rupture of membranes (PPROM), delivered 3 days post-operatively, and died. Two underwent EXIT to tracheostomy with one surviving to discharge and is currently 2 years old.ConclusionOur study demonstrates the outcomes of a large series of patients diagnosed with CHAOS. While mortality remains high, options for fetal intervention are being explored to allow alterations in the prenatal natural history and improve postnatal outcomes.Type of StudyRetrospective Treatment Study.Level of EvidenceLevel IV.     

Curative Laparoscopic Resection for Pancreatic Neoplasms: A Critical Analysis from a Single Institution

Laparoscopic pancreatic surgery (LPS) has seen significant development but much of the knowledge refers to small and benign pancreatic tumors. This study aims to evaluate the feasibility, safety, and long-term outcome of the laparoscopic approach in patients with benign, premalignant, and overt malignant lesions of the pancreas. This study, currently, is the largest single center experience worldwide. One hundred twenty-three consecutive patients underwent laparoscopic pancreatic surgery from April 1998 to April 2007, 20 patients with cysts or pseudocysts for acute and chronic pancreatitis, laparoscopic pancreatic drainage was performed, and were excluded from the analysis. The 103 patients were divided based on preoperative diagnosis: group I, inflammatory tumors for chronic pancreatitis (eight patients); group II, cystic pancreatic neoplasms (29 patients); group III, intraductal papillary mucinous neoplasms (10 patients); group IV, neuroendocrine pancreatic tumors (NETs) (43 patients); and group V ductal adenocarcinoma (13 patients). The median tumor size was 5.3 cm. Pathologic data include R ₀ or R ₁ resection (transection margins on the specimen were inked). Perioperative data, postoperative complications, and resection modalities were compared using statistical analysis. Long-term outcomes were analysed by tumor recurrence and patient survival. The overall conversion rate was 7%. Laparoscopic distal pancreatic resection was performed in 82 patients (79.6%). Laparoscopic spleen-preserving distal pancreatectomy (Lap SPDP) was performed in 52 patients (63.7%), but with splenic vessels preservation in 22% and without splenic vessels preservation in 41.5%. Laparoscopic en-bloc splenopancreatectomy (Lap SxDP) was performed in 30 patients (36.6%) and laparoscopic enucleation (Lap En) in 20 patients (19.4%). There was no mortality. The overall complication rate was 25.2, 16.7, and 40% after Lap SPDP, Lap SxDP, and Lap En, respectively. The overall morbidity rate was significantly higher (p > 0.05) in the group of Lap SPDP without splenic vessels preservation comparing with Lap SPDP with splenic vessels preservation because of the occurrence of splenic complications (20.6%). The overall pancreatic fistulas was 7.7, 10, and 35% after Lap SPDP, Lap SxDP, and Lap En, respectively; the severity of fistula was significantly higher in the Lap En group (p > 0.05). The mean hospital stay was within 1 week in all groups, except in the group of ductal adenocarcinoma, which is 8 days. In this series, 27 patients (26.2%) had malignant disease. R ₀ resection was achieved in 90% of ductal adenocarcinoma and 100% for other malignant tumors. The median survival for ductal adenocarcinoma patients was 14 months. This series demonstrates that LPS is feasible and safe in benign-appearing and malignant lesions of the pancreas.     

The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment

Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific antibodies in mammalian cells reveals mitotic phosphorylation of H3 Thr 3 in prophase and its dephosphorylation during anaphase. Furthermore we find that haspin, a member of a distinctive group of protein kinases present in diverse eukaryotes, phosphorylates H3 at Thr 3 in vitro. Importantly, depletion of haspin by RNA interference reveals that this kinase is required for H3 Thr 3 phosphorylation in mitotic cells. In addition to its chromosomal association, haspin is found at the centrosomes and spindle during mitosis. Haspin RNA interference causes misalignment of metaphase chromosomes, and overexpression delays progression through early mitosis. This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis.     

Monomères acryliques à fonction carbonate cyclique, 2 Modification chimique de copolymères à groupements carbonate cyclique lateraux

Acrylic monomers with a cyclic carbonate function, their synthesis having been described previously, are used to synthesize copolymers with pendent cyclic carbonate side groups. Their chemical modification by ring opening addition reactions provides a convenient method for preparing functional polymers. The study of reactions with amines, on model compounds and on polymers, shows the possibility of obtaining a macromolecular network with crosslinking groups of carbamate type.     

Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya

Although the alpha+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous alpha+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality-coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria.     

Diagnosis of intra-abdominal and mediastinal sarcoidosis with EUS-guided FNA

BACKGROUND: In the presence of a compatible clinical picture, the diagnosis of sarcoidosis requires pathologic confirmation of noncaseating epithelioid granuloma in affected tissues. The standard procedure of choice for most patients is a bronchoscopy with transbronchial biopsy (TBB), which has a diagnostic yield of 40% to 90%. The lowest yield with TBB is in cases that present with predominant mediastinal or intra-abdominal lymphadenopathy (LN) and minimal parenchymal lung involvement. OBJECTIVE: To study the diagnostic yield of EUS-guided FNA in diagnosing sarcoidosis with predominant LN or masses. DESIGN: Retrospective chart review. SETTING: Teaching university hospital. PATIENTS: Analysis of 21 consecutive patients with sarcoidosis and predominant mediastinal and/or intra-abdominal LN or masses who underwent EUS-guided FNA. RESULTS: EUS-guided FNA diagnosed sarcoidosis in 18 of 21 patients (86%). In 3 patients, EUS-guided FNA was either not diagnostic or inconclusive, and patients underwent mediastinoscopy with lymphadenectomy, which established the diagnosis of sarcoidosis. Seven of the 21 patients (33%) had intra-abdominal LN and/or masses, and EUS-guided FNA of the intra-abdominal pathology was diagnostic of sarcoidosis in 4 of the 7 patients (57%). Four of the 21 patients (19%) had a history of malignancy, and use of EUS-guided FNA helped in ruling out the recurrence of malignancy in 3 of the 4 patients (75%). LIMITATIONS: Mycobacterial and fungal culture was not obtained in all patients. CONCLUSIONS: EUS-guided FNA offers a practical, minimally invasive technique for the diagnosis of sarcoidosis in patients who present with predominant mediastinal and/or intra-abdominal LN or masses.