Improving Mental Health Support, Career Transitions and Access to Health Care for Surgical Residents.

OBJECTIVE: To increase access to mental health support, assist with career transitions, and improve access to health care. DESIGN: Retrospective survey data. SETTING: General surgery residency program. PARTICIPANTS: Surgical residents. RESULTS: We developed three programs to address the issues above. The "Fifth Tuesday of the Month" program allows residents to take time off during the first Tuesday morning of any month with five Tuesdays. The Physician Wellness Collaborative provides confidential, affordable, and easy-to-access counseling resources for residents. Residents are automatically signed up for a session to establish care. The Peer Resident Mentorship Program matches a fourth-year resident with a first-year resident based on personal and professional interests to help ease the transition and improve career satisfaction. All programs were associated with improvement in related outcome measures on our institution's annual program evaluation survey. CONCLUSIONS: At our institution, we introduced three simple and accessible programs aimed at increasing access to mental health support, assisting with career transitions, and improving work-life balance. These programs have improved related outcomes in our residents and can be easily implemented at any program.

Meta-analysis finds recurrent infection is more common after endovascular than after open repair of infected abdominal aortic aneurysm.

OBJECTIVE: Controversy has continued regarding the use of endovascular aneurysm repair (EVAR) vs open aneurysm repair (OAR) for infected abdominal aortic aneurysms (AAAs). In the present study, we investigated the comparative outcomes of EVAR and OAR for the treatment of infected AAAs. METHODS: We conducted a systematic review and meta-analysis using the MEDLINE and EMBASE databases through May 2021. We included studies that had described both EVAR and OAR for the treatment of infected AAAs. The primary endpoints were the rates of recurrent infection and related rupture and/or death. Perioperative and 1-year mortality and readmissions and reinterventions were also analyzed. RESULTS: Fourteen observational studies describing a total of 1203 patients (EVAR, 359 [29.8%]; OAR, 844 [70.2%]) were eligible for qualitative analysis. The baseline characteristics included diabetes mellitus (33.2%), fever at presentation (71.6%), rupture at diagnosis (26.1%), and positive blood cultures (52.5%). The mean follow-up period ranged from 12 to 40 months. The use of EVAR became more prevalent in recent years (2016-2020, 32.4%) compared with the former period (2010-2015, 13.8%; P < .0001). Fenestrated, branched, or concomitant visceral debranching EVAR was performed in 6.1% of cases. In OAR, surgical debridement was consistently performed, and in situ reconstruction was applied in 82.2% and an omental flap in 51.5%. In nine studies considered for quantitative analysis, the patients' background (EVAR, n = 264; OAR, n = 274) were statistically balanced. The crude rates of recurrent infection and related rupture or death were 13.6% (95% confidence interval [CI], 8.8%-18.5%) and 4.9% (95% CI 1.8%-8.0%), respectively. The pooled analyses depicted significantly higher rates of recurrent infection after EVAR than after OAR (relative risk [RR], 2.42; 95% CI, 1.80-3.27; P < .0001; I2 = 0%). Recurrent infection-related rupture or death (RR, 1.51; 95% CI, 0.70-3.23; P = .29; I2 = 0%), perioperative death (RR, 0.80; 95% CI, 0.39-1.65; P = .55; I2 = 35%), 1-year mortality (hazard ratio, 1.12; 95% CI, 0.97-1.28; P =.13; I2 = 0%), and readmission or reintervention (RR, 1.16; 95% CI, 0.74-1.82; P =.52; I2 = 0%) were not significantly different statistically between the two groups. Funnel plots showed no evidence of publication bias. Sensitivity analyses of leave-one-out meta-analysis confirmed higher rates of recurrent infection after EVAR. CONCLUSIONS: EVAR has become more prevalent as the initial treatment of infected AAAs. Although operative and 1-year survival were similar between OAR and EVAR groups, recurrent infection was more frequent after EVAR. This limitation should be weighed in selecting patients for EVAR in infected AAAs. Postoperative graft and infection surveillance are critical, especially after EVAR.

The role of mutant UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 in regulating serum intact fibroblast growth factor 23 and matrix extracellular phosphoglycoprotein in heritable tumoral calcinosis.

CONTEXT: Familial tumoral calcinosis (TC) results from disruptions in phosphate metabolism and is characterized by high serum phosphate with normal or elevated 1,25 dihydroxyvitamin vitamin D concentrations and ectopic and vascular calcifications. Recessive loss-of-function mutations in UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and fibroblast growth factor-23 (FGF23) result in TC. OBJECTIVE: The objective of the study was to determine the relationship between GALNT3 and FGF23 in familial TC. DESIGN, SETTING, AND PATIENTS: We assessed the major biochemical defects and potential genes involved in patients with TC. INTERVENTION: Combination therapy consisted of the phosphate binder Sevelamer and the carbonic anhydrase inhibitor acetazolamide. RESULTS: We report a patient homozygous for a GALNT3 exon 1 deletion, which is predicted to truncate the encoded protein. This patient had high serum FGF23 concentrations when assessed with a C-terminal FGF23 ELISA but low-normal FGF23 levels when tested with an ELISA for intact FGF23 concentrations. Matrix extracellular phosphoglycoprotein has been identified as a possible regulator of phosphate homeostasis. Serum matrix extracellular phosphoglycoprotein levels, however, were normal in the family with GALNT3-TC and a kindred with TC carrying the FGF23 S71G mutation. The tumoral masses of the patient with GALNT3-TC completely resolved after combination therapy. CONCLUSIONS: Our findings demonstrate that GALNT3 inactivation in patients with TC leads to inadequate production of biologically active FGF23 as the most likely cause of the hyperphosphatemic phenotype. Furthermore, combination therapy may be effective for reducing the tumoral burden associated with familial TC.

Fibroblast growth factor-23 mutants causing familial tumoral calcinosis are differentially processed.

Familial tumoral calcinosis (TC, OMIM 211900) is a heritable disorder characterized by hyperphosphatemia, normal or elevated serum 1,25-dihydroxyvitamin D, and often severe ectopic calcifications. Two recessive mutations in fibroblast growth factor-23 (FGF23), serine 71/glycine (S71G) and serine 129/phenylalanine (S129F), were identified as causing TC. Herein, we undertook comprehensive biochemical analyses of an extended TC family carrying the S71G FGF23 mutation, which revealed that heterozygous (serine/glycine, S/G) individuals had elevated serum FGF23 C-terminal fragments compared with wild-type (serine/serine, S/S) family members (P < 0.025). To understand the differential processing of FGF23 in TC patients, we transiently expressed S71G as well as S129F FGF23. FGF23 ELISA in tandem with Western analyses revealed increased proteolytic cleavage of mutant FGF23 and a limited secretion of intact protein. Furthermore, S71G and S129F FGF23 carrying mutations that disrupt the furin-like protease RXXR motif in FGF23 rescued the secretion of the intact protein, and both TC mutant proteins harboring the R176Q mutation revealed no altered sensitivity to trypsin compared with the native (R176Q)FGF23. Finally, S71G, but not S129F mutant FGF23, is rescued by temperature. In summary, FGF23 mutations causing TC lead to increased intracellular proteolysis of FGF23, most likely by furin-like proteases, due to conformational changes of the mutant protein. The destabilizing nature of these mutations provides new insight into the pathophysiology of TC and exemplifies the physiological importance of FGF23 in phosphate and vitamin D metabolism.

A novel recessive mutation in fibroblast growth factor-23 causes familial tumoral calcinosis.

Gain-of-function mutations in fibroblast growth factor-23 (FGF23) are responsible for autosomal dominant hypophosphatemic rickets, a disorder of isolated renal phosphate wasting. Patients with the disorder display hypophosphatemia with normocalcemia as well as inappropriately normal 1,25-dihydroxyvitamin D [1,25(OH)2D3] concentrations. Reciprocally tumoral calcinosis (TC) patients are often hyperphosphatemic with inappropriately normal or elevated serum 1,25(OH)2D3 levels and have ectopic and vascular calcifications, a phenotype similar to that of Fgf23 null mice. Therefore, the goal of the present studies was to test whether FGF23 was a candidate gene for TC. Two sisters in a consanguineous TC family had hyperphosphatemia and normal 1,25(OH)2D3 levels with characteristic ectopic and vascular calcifications. Interestingly, these patients had low-normal intact serum FGF23 levels but demonstrated FGF23 concentrations approximately 40 times normal when assessed with a C-terminal FGF23 serum assay. Mutational analyses identified a homozygous S71G mutation in FGF23 in the TC patients, which was not found in control alleles. Finally, modeling demonstrated that the S71G mutation most likely destabilizes full-length FGF23. In summary, recessive FGF23 mutations can lead to TC. Additionally, our findings indicate that FGF23 may adopt an unstable conformation in some TC patients, possibly leading to nonfunctional FGF23 protein.