Trial Participation and Outcomes Among English-Speaking and Spanish-Speaking Patients With Appendicitis Randomized to Antibiotics: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: Spanish-speaking participants are underrepresented in clinical trials, limiting study generalizability and contributing to ongoing health inequity. The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial intentionally included Spanish-speaking participants. Objective: To describe trial participation and compare clinical and patient-reported outcomes among Spanish-speaking and English-speaking participants with acute appendicitis randomized to antibiotics. Design, Setting, and Participants: This study is a secondary analysis of the CODA trial, a pragmatic randomized trial comparing antibiotic therapy with appendectomy in adult patients with imaging-confirmed appendicitis enrolled at 25 centers across the US from May 1, 2016, to February 28, 2020. The trial was conducted in English and Spanish. All 776 participants randomized to antibiotics are included in this analysis. The data were analyzed from November 15, 2021, through August 24, 2022. Intervention: Randomization to a 10-day course of antibiotics or appendectomy. Main Outcomes and Measures: Trial participation, European Quality of Life-5 Dimensions (EQ-5D) questionnaire scores (higher scores indicating a better health status), rate of appendectomy, treatment satisfaction, decisional regret, and days of work missed. Outcomes are also reported for a subset of participants that were recruited from the 5 sites with a large proportion of Spanish-speaking participants. Results: Among eligible patients 476 of 1050 Spanish speakers (45%) and 1076 of 3982 of English speakers (27%) consented, comprising the 1552 participants who underwent 1:1 randomization (mean age, 38.0 years; 976 male [63%]). Of the 776 participants randomized to antibiotics, 238 were Spanish speaking (31%). Among Spanish speakers randomized to antibiotics, the rate of appendectomy was 22% (95% CI, 17%-28%) at 30 days and 45% (95% CI, 38%-52%) at 1 year, while in English speakers, these rates were 20% (95% CI, 16%-23%) at 30 days and 42% (95% CI 38%-47%) at 1 year. Mean EQ-5D scores were 0.93 (95% CI, 0.92-0.95) among Spanish speakers and 0.92 (95% CI, 0.91-0.93) among English speakers. Symptom resolution at 30 days was reported by 68% (95% CI, 61%-74%) of Spanish speakers and 69% (95% CI, 64%-73%) of English speakers. Spanish speakers missed 6.69 (95% CI, 5.51-7.87) days of work on average, while English speakers missed 3.76 (95% CI, 3.20-4.32) days. Presentation to the emergency department or urgent care, hospitalization, treatment dissatisfaction, and decisional regret were low for both groups. Conclusions and Relevance: A high proportion of Spanish speakers participated in the CODA trial. Clinical and most patient-reported outcomes were similar for English- and Spanish-speaking participants treated with antibiotics. Spanish speakers reported more days of missed work. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Perception of Treatment Success and Impact on Function with Antibiotics or Appendectomy for Appendicitis: A Randomized Clinical Trial with an Observational Cohort.

OBJECTIVE: To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days. SUMMARY BACKGROUND DATA: The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes. METHODS: We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations. RESULTS: The pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05-4.31) and dissatisfaction (OR 1.98, 95%CI 1.25-3.12), and reported less missed work (OR 0.39, 95%CI 0.27-0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret. CONCLUSIONS: Overall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02800785.

Association of Patient Belief About Success of Antibiotics for Appendicitis and Outcomes: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials. Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis. Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful. Main Outcomes and Measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors. Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28). Conclusions and Relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Analysis of Outcomes Associated With Outpatient Management of Nonoperatively Treated Patients With Appendicitis.

Importance: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs. Objective: To assess the use and safety of outpatient management of acute appendicitis. Design, Setting, and Participants: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020. Exposures: Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively. Main Outcomes and Measures: Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared. Results: Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores. Conclusions and Relevance: These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Self-selection vs Randomized Assignment of Treatment for Appendicitis.

Importance: For adults with appendicitis, several randomized clinical trials have demonstrated that antibiotics are an effective alternative to appendectomy. However, it remains unknown how the characteristics of patients in such trials compare with those of patients who select their treatment and whether outcomes differ. Objective: To compare participants in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial (RCT) with a parallel cohort study of participants who declined randomization and self-selected treatment. Design, Setting, and Participants: The CODA trial was conducted in 25 US medical centers. Participants were enrolled between May 3, 2016, and February 5, 2020; all participants were eligible for at least 1 year of follow-up, with all follow-up ending in 2021. The randomized cohort included 1094 adults with appendicitis; the self-selection cohort included patients who declined participation in the randomized group, of whom 253 selected appendectomy and 257 selected antibiotics. In this secondary analysis, characteristics and outcomes in both self-selection and randomized cohorts are described with an exploratory analysis of cohort status and receipt of appendectomy. Interventions: Appendectomy vs antibiotics. Main Outcomes and Measures: Characteristics among participants randomized to either appendectomy or antibiotics were compared with those of participants who selected their own treatment. Results: Clinical characteristics were similar across the self-selection cohort (510 patients; mean age, 35.8 years [95% CI, 34.5-37.1]; 218 female [43%; 95% CI, 39%-47%]) and the randomized group (1094 patients; mean age, 38.2 years [95% CI, 37.4-39.0]; 386 female [35%; 95% CI, 33%-38%]). Compared with the randomized group, those in the self-selection cohort were less often Spanish speaking (n = 99 [19%; 95% CI, 16%-23%] vs n = 336 [31%; 95% CI, 28%-34%]), reported more formal education (some college or more, n = 355 [72%; 95% CI, 68%-76%] vs n = 674 [63%; 95% CI, 60%-65%]), and more often had commercial insurance (n = 259 [53%; 95% CI, 48%-57%] vs n = 486 [45%; 95% CI, 42%-48%]). Most outcomes were similar between the self-selection and randomized cohorts. The number of patients undergoing appendectomy by 30 days was 38 (15.3%; 95% CI, 10.7%-19.7%) among those selecting antibiotics and 155 (19.2%; 95% CI, 15.9%-22.5%) in those who were randomized to antibiotics (difference, 3.9%; 95% CI, -1.7% to 9.5%). Differences in the rate of appendectomy were primarily observed in the non-appendicolith subgroup. Conclusions and Relevance: This secondary analysis of the CODA RCT found substantially similar outcomes across the randomized and self-selection cohorts, suggesting that the randomized trial results are generalizable to the community at large. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Overriding impaired FPR chemotaxis signaling in diabetic neutrophil stimulates infection control in murine diabetic wound.

Infection is a major co-morbidity that contributes to impaired healing in diabetic wounds. Although impairments in diabetic neutrophils have been blamed for this co-morbidity, what causes these impairments and whether they can be overcome, remain largely unclear. Diabetic neutrophils, isolated from diabetic individuals, exhibit chemotaxis impairment but this peculiar functional impairment has been largely ignored because it appears to contradict the clinical findings which blame excessive neutrophil influx as a major impediment to healing in chronic diabetic ulcers. Here, we report that exposure to glucose in diabetic range results in impaired chemotaxis signaling through the formyl peptide receptor (FPR) in neutrophils, culminating in reduced chemotaxis and delayed neutrophil trafficking in the wound of Leprdb (db/db) type two diabetic mice, rendering diabetic wound vulnerable to infection. We further show that at least some auxiliary receptors remain functional under diabetic conditions and their engagement by the pro-inflammatory cytokine CCL3, overrides the requirement for FPR signaling and substantially improves infection control by jumpstarting the neutrophil trafficking toward infection, and stimulates healing in diabetic wound. We posit that CCL3 may have therapeutic potential for the treatment of diabetic foot ulcers if it is applied topically after the surgical debridement process which is intended to reset chronic ulcers into acute fresh wounds.

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis.

BACKGROUND: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).

Successful Reinnervation of the Diaphragm After Intercostal to Phrenic Nerve Neurotization in Patients With High Spinal Cord Injury.

OBJECTIVE: Our objective in this study was to extend diaphragmatic pacing therapy to include paraplegic patients with high cervical spinal cord injuries between C3 and C5. INTRODUCTION: Diaphragmatic pacing has been used in patients experiencing ventilator-dependent respiratory failure due to spinal cord injury as a means to reduce or eliminate the need for mechanical ventilation. However, this technique relies on intact phrenic nerve function. Recently, phrenic nerve reconstruction with intercostal nerve grafting has expanded the indications for diaphragmatic pacing. Our study aimed to evaluate early outcomes and efficacy of intercostal nerve transfer in diaphragmatic pacing. METHODS: Four ventilator-dependent patients with high cervical spinal cord injuries were selected for this study. Each patient demonstrated absence of phrenic nerve function via external neck stimulation and laparoscopic diaphragm mapping. Each patient underwent intercostal to phrenic nerve grafting with implantation of a phrenic nerve pacer. The patients were followed, and ventilator dependence was reassessed at 1 year postoperatively. RESULTS: Our primary outcome was measured by the amount of time our patients tolerated off the ventilator per day. We found that all 4 patients have tolerated paced breathing independent of mechanical ventilation, with 1 patient achieving 24 hours of tracheostomy collar. CONCLUSIONS: From this study, intercostal to phrenic nerve transfer seems to be a promising approach in reducing or eliminating ventilator support in patients with C3 to C5 high spinal cord injury.

Dual Kidney Allocation Score: A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults.

BACKGROUND Dual kidney transplantation (DKT) of expanded-criteria donors is a cost-intensive procedure that aims to increase the pool of available deceased organ donors and has demonstrated equivalent outcomes to expanded-criteria single kidney transplantation (eSKT). The objective of this study was to develop an allocation score based on predicted graft survival from historical dual and single kidney donors. MATERIAL AND METHODS We analyzed United Network for Organ Sharing (UNOS) data for 1547 DKT and 26 381 eSKT performed between January 1994 and September 2013. We utilized multivariable Cox regression to identify variables independently associated with graft survival in dual and single kidney transplantations. We then derived a weighted multivariable product score from calculated hazard ratios to model the benefit of transplantation as dual kidneys. RESULTS Of 36 donor variables known at the time of listing, 13 were significantly associated with graft survival. The derived dual allocation score demonstrated good internal validity with strong correlation to improved survival in dual kidney transplants. Donors with scores less than 2.1 transplanted as dual kidneys had a worsened median survival of 594 days (24%, p-value 0.031) and donors with scores greater than 3.9 had improved median survival of 1107 days (71%, p-value 0.002). There were 17 733 eSKT (67%) and 1051 DKT (67%) with scores in between these values and no differences in survival (p-values 0.676 and 0.185). CONCLUSIONS We have derived a dual kidney allocation score (DKAS) with good internal validity. Future prospective studies will be required to demonstrate external validity, but this score may help to standardize organ allocation for dual kidney transplantation.

A 22-year-old man with pleural tuberculosis associated hydropneumothorax: Case report and literature review.

A 22-year-old Asian male presented with fever, non-productive cough, right-sided pleuritic chest pain and was found to have a large right hydropneumothorax. A chest tube was placed. Pleural fluid analysis revealed a lymphocytic predominant exudate and he was subsequently started on four-drug daily anti-tuberculosis therapy (isoniazid, ethambutol, rifampin, pyrazinamide). Pleural biopsy revealed acid-fast bacilli. Given his persistent pleural effusion, he was given four doses of intrapleural tissue plasminogen activator (tPA) and dornase alpha (DNase) via his chest tube over a period of 6 days resulting in clinical and radiologic improvement. Pleural biopsy and pleural fluid culture specimens later revealed Mycobacterium tuberculosis. Intrapleural tPA-DNase therapy has demonstrated improved resolution of infections and shortened hospitalizations for parapneumonic infectious effusions. However, there is little literature on the use of intrapleural fibrinolytics specifically for pleural tuberculosis associated effusions. Furthermore, the American Thoracic Society does not comment on therapeutic thoracentesis or intrapleural fibrinolytic therapy in their recommendations for treatment of pleural tuberculosis. In our case of pleural TB-associated hydropneumothorax, the use of intrapleural tPA-DNase therapy facilitated pleural fluid drainage and resulted in near-complete resolution of the effusion.

Intraductal Papillary Mucinous Neoplasm of the Pancreas Arising in the Setting of an Intermixed Acinar Cell Cystadenoma of the Pancreas: Report of a Rare Case.

Background: Synchronous cystic lesions of the pancreas with different pathophysiology in the same patient are a rare occurrence.. Case Presentation: We report the incidental finding of a multicystic lesion within the pancreatic head in a morbidly obese woman during workup for bariatric surgery. The lesion contained an intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia within an acinar cell cystadenoma (ACA). ACAs are rare tumors first described in 2002. Conclusion: To date, there have been no published reports of synchronous IPMN within an ACA. This case report intends to increase provider awareness of these lesions as well as highlight the importance of surveillance and careful histological examination of heterogeneous cystic lesions of the pancreas.

Juxta-articular joint-capsule mineralization in CD73 deficient mice: similarities to patients with NT5E mutations.

Arterial calcification due to CD73 deficiency (ACDC), an autosomal recessive disorder, manifests with extensive mineralization of the lower-extremity arteries as well as of hand and foot joint-capsules. This disease is caused by mutations in the NT5E gene which encodes CD73, a membrane-bound ecto-5'-nucleotidase hydrolyzing 5'-AMP into adenosine and Pi. To gain insight into the pathophysiologic details of ACDC, we have characterized a Nt5e(-/-) knock out mouse (Nt5e(tm1Jgsc)) deficient in CD73. These mice, when maintained on appropriate strain background, demonstrated stiffening of the joints and micro CT revealed distinct changes in the thoracic skeletal structure with evidence of mineralization at the costochondral junctions. Mineralization was also noted in the juxta-articular spaces of the lower extremities as well as of ligaments and capsules adjacent to the bony structures. No evidence of vascular mineralization was noted either by CT or by microdissection of arteries in the thoracic area or in lower extremities. The Nt5e(-/-) mutant mice demonstrated significantly increased Pi levels in the serum and significantly reduced PPi concentration in the heparinized plasma, resulting in markedly increased Pi/PPi ratio, thus creating a pro-mineralization environment. In conclusion, the Nt5e(-/-) targeted mutant mice recapitulate some, but not all, features of ACDC and serve as a model system to study pharmacologic interventions for ectopic mineralization. Collectively, this mouse model deficient in CD73, with other targeted mutant mice with vascular mineralization, attests to the presence of a complex pro-mineralization/anti-mineralization network that under physiologic homeostatic conditions prevents ectopic tissue mineralization.

Genetic modulation of nephrocalcinosis in mouse models of ectopic mineralization: the Abcc6(tm1Jfk) and Enpp1(asj) mutant mice.

Ectopic mineralization of renal tissues in nephrocalcinosis is a complex, multifactorial process. The purpose of this study was to examine the role of genetic modulation and the role of diet in nephrocalcinosis using two established mouse models of ectopic mineralization, Abcc6(tm1Jfk) and Enpp1(asj) mice, which serve as models for pseudoxanthoma elasticum and generalized arterial calcification of infancy, two heritable disorders, respectively. These mutant mice, when on standard rodent diet, develop nephrocalcinosis only at a very late age. In contrast, when placed on an 'acceleration diet' composed of increased phosphate and reduced magnesium content, they showed extensive mineralization of the kidneys affecting primarily the medullary tubules as well as arcuate and renal arteries, as examined by histopathology and quantitated by chemical assay for calcium. Mineralization could also be detected noninvasively by micro computed tomography. Whereas the heterozygous mice did not develop nephrocalcinosis, compound heterozygous mice carrying both mutant alleles, Abcc6(tm1Jfk/+) and Enpp1(+/asj), developed ectopic mineralization similar to that noted in homozygous mice for either gene, indicating that deletion of one Abcc6 allele along with Enpp1 haploinsufficiency resulted in renal mineralization. Thus, synergistic genetic defects in the complex mineralization/antimineralization network can profoundly modulate the degree of ectopic mineralization in nephrocalcinosis.

Perioperative visual loss after excision and autografting of a thermal burn to the back.

Peri-operative visual loss is an uncommon and poorly understood entity whose severity launched a Practice Advisory to identify peri-operative risk factors including prone positioning, anemia, hypotension, blood loss >44.7% of EBV, and surgical time >4-6.5 h. Contributing co-morbidities are obesity, tobacco, malnutrition, and PAD, which reduce blood flow to the optic nerve. We describe a patient with POVL focusing on the peri-operative course defined as the immediate preoperative assessment through discharge to compare the hospital course with previous reports of POVL in cardiac and spine operations.ss A middle-aged man admitted to the burn unit with 10% deep partial and full thickness burns to the back and neck underwent excision and autografting while prone. He was subsequently diagnosed with ischemic optic neuropathy and blindness. Co-morbidities were tobacco, malnutrition (albumin of 2.6 g/dl), and obesity (BMI 30.1). Preoperative risk assessment included anemia and prone positioning. Intra-operative hypotension to SBP 75 mmHg was noted. Operative duration was 5 h. Blood loss was estimated to be 43.7% of EBV. Risk factors for POVL are present in many prone burn operations as these patients have long operative times and significant blood loss. Thus, minimization of these factors where possible is advised.

Middle aortic coarctation.

BACKGROUND: Middle aortic coarctation (MAC), a variant of middle aortic syndrome, is a rare entity with only ∼200 cases described in the literature. It classically presents with early onset and refractory hypertension, abdominal angina, and lower extremity claudication. Although endovascular repair has been described for focal stenoses, open bypass remains the standard to restore abdominal inflow and correct renovascular hypertension. METHODS: We describe an unusually late presentation of MAC in a 52-year-old man from El Salvador with refractory hypertension since age 8 requiring 5 antihypertensive medications. He presented with acute chest pain and severe hypertension. He denied mesenteric and peripheral vascular symptoms. Distal pulses were not palpable. Creatinine was 1.9 mg/dL (peak 4.0 mg/dL). Computed tomography angiography demonstrated coarctation of the descending thoracic aorta with extensive collateralization. RESULTS: After control of blood pressure, the patient's singular anatomy dictated a descending thoracic aorta-infrarenal aortic bypass using a 16-mm woven Hemashield tube graft via a left fifth-interspace anterolateral thoracotomy and left retroperitoneal incision. The graft was tunneled through the posterior left hemidiaphragm. Patient had excellent recovery, with decrease in antihypertensive medications (5 to 2), restoration of all distal pulses, and no neurologic complications. Postoperative creatinine was 0.9 mg/dL. CONCLUSIONS: MACs are rare entities with presentation usually in youth or adolescence, comprising only 0.5-2% of all aortic coarctation cases. Etiologies include congenital, acquired, inflammatory, and infectious causes. If untreated, most patients do not survive past the fourth decade because of the sequelae of renovascular hypertension including myocardial infarction, heart failure, intracranial hemorrhage, and aortic rupture. Depending on technical considerations, open surgical bypass remains the standard repair for MAC.