Treatment of metastatic rectal squamous cell carcinoma in a pregnant patient.

Rectal squamous cell carcinoma is an exceedingly rare form of rectal cancer, with limited data available regarding its presentation and effective treatment. Rectal cancer occurring during pregnancy is uncommon as well. This is a case of metastatic rectal squamous cell carcinoma presenting in a 22-week pregnant, female patient in her early 30s. The patient was treated with 5-fluorouracil and cisplatin and delivered a healthy male child born via uncomplicated vaginal delivery at 35 weeks. This article demonstrates that despite the rare nature of this cancer, in the already rare context of pregnancy, effective and safe treatment is possible with a multidisciplinary team.

Exploring the effects of racial and socioeconomic factors on timeliness of lung cancer diagnosis and treatment in Baltimore Veterans.

OBJECTIVES: To characterize the effect of racial and socioeconomic factors on the timeliness of lung cancer diagnosis and treatment in a single-center Veterans Affair Medical Center (VAMC) pulmonary nodule clinic. METHODS: We conducted a single-center retrospective review of all patients seen at the Baltimore VAMC pulmonary nodule clinic between 2013 and 2019 to identify key demographic factors, measures of neighborhood socioeconomic disadvantage, cancer staging and histopathologic information, and time elapsed between diagnosis and treatment. We excluded patients with pulmonary nodules undergoing active surveillance, prior history of lung cancer, metastases of a different primary origin, insufficient followup, or who had received care outside the VHA system. RESULTS: Median times to diagnosis and treatment of lung cancer were 28 and 73 days. There were no statistically significant differences in overall timeliness of diagnosis and treatment when stratified by race or measures of neighborhood socioeconomic disadvantage. CONCLUSIONS: The authors found no differences in timeliness of lung cancer care by race and socioeconomic status within the system. Despite general adherence to national standards in timeliness of care, there continues to be a need for improvements in the operational workflows to reduce time to diagnosis and treatment for all Veterans.

Sepsis and septic shock after craniotomy: Predicting a significant patient safety and quality outcome measure.

OBJECTIVES: Sepsis and septic shock are important quality and patient safety metrics. This study examines incidence of Sepsis and/or septic shock (S/SS) after craniotomy for tumor resection, one of the most common neurosurgical operations. METHODS: Multicenter, prospectively collected data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was used to identify patients undergoing craniotomy for tumor (CPT 61510, 61521, 61520, 61518, 61526, 61545, 61546, 61512, 61519, 61575) from 2012-2015. Univariate and multivariate logistic regression models were used to identify risk factors for S/SS. RESULTS: There were 18,642 patients that underwent craniotomy for tumor resection. The rate of sepsis was 1.35% with a mortality rate of 11.16% and the rate of septic shock was 0.65% with a 33.06% mortality rate versus an overall mortality rate of 2.46% in the craniotomy for tumor cohort. The 30-day readmission rate was 50.54% with S/SS vs 10.26% in those without S/SS. Multiple factors were identified as statistically significant (p <0.05) for S/SS including ascites (OR = 33.0), ventilator dependence (OR = 4.5), SIRS (OR = 2.8), functional status (OR = 2.3), bleeding disorders (OR = 1.7), severe COPD (OR = 1.6), steroid use (OR = 1.6), operative time >310 minutes (OR = 1.5), hypertension requiring medication (OR = 1.5), ASA class ≥ 3 (OR = 1.4), male sex (OR = 1.4), BMI >35 (OR = 1.4) and infratentorial location. CONCLUSIONS: The data indicate that sepsis and septic shock, although uncommon after craniotomy for tumor resection, carry a significant risk of 30-day unplanned reoperation (35.60%) and mortality (18.21%). The most significant risk factors are ventilator dependence, ascites, SIRS and poor functional status. By identifying the risk factors for S/SS, neurosurgeons can potentially improve outcomes. Further investigation should focus on the creation of a predictive score for S/SS with integration into the electronic health record for targeted protocol initiation in this unique neurosurgical patient population.

FGF23 is endogenously phosphorylated in bone cells.

Levels of serum phosphate are controlled by the peptide hormone FGF23, secreted from bone osteocytes. Elevated levels of circulating FGF23 are a key factor in several hypophosphatemic disorders and play a role in chronic kidney disease. Posttranslational processing of FGF23 includes multi-site O-glycosylation, which reduces intracellular cleavage by proprotein convertases. The FGF23 protein also contains four serine phosphorylation consensus sequences (S-X-D/E); in this work, we asked whether FGF23 is a substrate for secretory phosphorylation. Both HEK cells as well as IDG-SW3 cells, an osteocyte model, incorporated radiolabeled orthophosphate into intact FGF23, as well as into the 14-kDa carboxy-terminal-but not the 17-kDa N-terminal-fragment. Sequential serine-to-alanine site-directed mutagenesis of four kinase consensus sites showed that labeling occurred on three serines within the carboxy-terminal fragment, Ser180 (adjacent to the cleavage site), Ser207, and Ser212. Liquid chromatography-coupled mass spectroscopy indicated the presence of phosphate at Ser212 in recombinant R&D mouse FGF23(R179Q) , confirming labeling results. A phosphopeptide-specific antibody was raised against phospho-Ser212 and exhibited immunoreactivity in osteocytes present in mouse long bone, providing further evidence that FGF23 is naturally phosphorylated in bone. Bone SIBLING proteins are serine-phosphorylated by the ubiquitous Golgi secretory kinase FAM20C. Cotransfection of HEK and MC3T3 cells with FGF23 and active, but not inactive, FAM20C kinase increased the storage and release of FGF23 in radiolabeling experiments, indicating potential effects of phosphorylation on FGF23 stability. Collectively, these data point to an important role for phosphorylation of FGF23 in bone.