Multiple Internal Hernias: A Complication of Laparoscopic Roux-en-Y Gastric Bypass.

Introduction: Internal hernias are the most common cause of small bowel obstruction following laparoscopic Roux-en-Y gastric bypass surgery (LRYGBP) with four distinct types. Herein, we report the clinical course of a patient with two independent hernias at the Petersen's space and a rarer subtype at the jejunojejunal window. A high index of suspicion for less common subtypes of internal hernias and the possibility of multiple, simultaneous internal hernias is critical. Case Description: We describe the case of a 52-year-old female with a history of LRYGBP who presented with abdominal pain and emesis due to an internal hernia at Peterson's defect, requiring subsequent laparoscopic repair. On postoperative day three, the patient presented again with recurrent abdominal pain and emesis. Repeat exploratory laparoscopy found a separate internal hernia involving the jejunojejunal window with the previously repaired Petersen's defect intact. Discussion: This case illustrates a unique scenario of a patient post-LRYGBP with multiple internal hernias at the Peterson's space and the less common jejunojejunal window, which was missed during the index surgery. Failure to identify simultaneous hernias may result in additional invasive intervention and further morbidity. Conclusion: Multiple less-common variants of internal hernias may present simultaneously following LRYGBP.

Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life.

The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, the antibody appeared to adhere to pipette tips, requiring tips to be changed during serial dilution to accurately measure potency. Second, during production scale-up, proteolytic cleavage was discovered to target an extended heavy chain loop, which was attributed to a protease in spent medium from 2-week culture. To enable large scale production, we altered the site of cleavage via a single amino acid change, K100mA. The resultant antibody retained potency and breadth while avoiding protease cleavage. We also added the half-life extending mutation LS, which improved the in vivo persistence in animal models, but did not impact neutralization activity; we observed the same preservation of neutralization for bNAbs VRC01, N6, and PGDM1400 with LS on a 208-virus panel. The final engineered antibody, CAP256V2LS, retained the extraordinary neutralization potency of the parental antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate.