Non Breast-Milk-Fed Very Preterm Infants Are at Increased Risk of Iron Deficiency at 4-6-Months Corrected Age: A Retrospective Population-Based Cohort Study.

Iron supplementation is routinely recommended for breast-milk-fed preterm infants. However, the Canadian Pediatric Society recommends no additional iron supplementation for preterm infants fed primarily with iron-rich formula. Other pediatric societies don't provide specific guidance on supplemental iron for formula-fed preterm infants. This study investigated how feeding type influences iron status of very preterm infants at 4-6-months corrected age (CA). A retrospective cohort study was conducted using a population-based database on all very preterm infants (<31 weeks gestational age) born in Nova Scotia, Canada from 2005-2018. Information about feeding type, iron intake from formula, supplemental iron therapy and iron status at 4-6-months CA was extracted. Iron deficiency (ID) was defined as serum ferritin <20 and <12 µg/L at 4-and 6-months CA, respectively. Of 392 infants, 107 were "breast-milk-fed" (exclusively or partially) and 285 were "not breast-milk-fed" (exclusively fed with iron-rich formula) at 4-6-months CA. Total daily iron intake was higher in the non-breast-milk-fed group (2.6 mg/kg/day versus 2.0 mg/kg/day). Despite this, 36.8% of non-breast-milk-fed infants developed ID versus 20.6% of breast-milk-fed infants. ID is significantly more prevalent in non-breast-milk-fed infants than breast-milk-fed infants despite higher iron intake. This suggests the need to revisit recommendations for iron supplementation in non-breast-milk-fed preterm infants.

Low Skeletal Muscle as a Risk Factor for Worse Survival in Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus.

BACKGROUND: Renal cell carcinoma (RCC) with tumor thrombosis often requires nephrectomy and tumor thrombectomy. As an extensive and potentially morbid operation, patient preoperative functional reserve and body composition is an important consideration. Sarcopenia is a risk factor for increased postoperative complications, systemic therapy toxicity, and death solid organ tumors, including RCC. The influence of sarcopenia in RCC patients with tumor thrombus is not well defined. This study evaluates the prognostic ability of sarcopenia regarding surgical outcomes and complications in patients undergoing surgery for RCC with tumor thrombus. METHODS: We retrospectively analyzed patients with nonmetastatic RCC and tumor thrombus undergoing radical nephrectomy and tumor thrombectomy. Skeletal muscle index (SMI; cm2/m2) was measured on preoperative CT/MRI. Sarcopenia was defined using body mass index- and sex-stratified thresholds optimally fit via a receiver-operating characteristic analysis for survival. Associations between preoperative sarcopenia and overall (OS), cancer-specific survival (CSS), and 90-day major complications were determined using multivariable analysis. RESULTS: 115 patients were analyzed, with median (IQR) age and body mass index of 69 (56-72) and 28.6 kg/m2 (23.6-32.9), respectively. 96 (83.4%) of the cohort had ccRCC. Sarcopenia was associated with shorter median OS (P = .0017) and CSS (P = .0019) in Kaplan-Meier analysis. In multivariable analysis, preoperative sarcopenia was prognostic of shorter OS (HR = 3.38, 95% confidence interval [CI] 1.61-7.09) and CSS (HR = 5.15, 95% CI 1.46-18.18). Notably, 1 unit increases in SMI were associated with improved OS (HR = 0.97, 95% CI 0.94-0.999) but not CSS (HR = 0.95, 95% CI 0.90-1.01). No significant relationship between preoperative sarcopenia and 90-day major surgical complications was observed in this cohort (HR = 2.04, 95% CI 0.65-6.42). CONCLUSION: Preoperative sarcopenia was associated with decreased OS and CSS in patients surgically managed for nonmetastatic RCC and VTT, however, was not predictive of 90-day major postoperative complications. Body composition analysis has prognostic utility for patients with nonmetastatic RCC and venous tumor thrombus undergoing surgery.

Prognostic Value of Sarcopenia and Albumin in the Surgical Management of Localized Renal Cell Carcinoma.

INTRODUCTION: A universally accepted model for preoperative surgical risk stratification in localized RCC patients undergoing nephrectomy is currently lacking. Both the evaluation of body composition and nutritional status has demonstrated prognostic value for patients with cancer. This study aims to investigate the potential associations between sarcopenia and hypoalbuminemia and survival outcomes in patients with localized kidney cancer treated with partial or radical nephrectomy. MATERIALS AND METHODS: We retrospectively analyzed 473 patients with localized RCC managed with radical and partial nephrectomy. Skeletal muscle index (SMI) was measured from preoperative CT and MRI. Sarcopenic criteria were created using BMI- and sex-stratified thresholds. Relationships between sarcopenia and hypoalbuminemia (Albumin <3.5 g/dL) with overall (OS), recurrence-free (RFS), and cancer-specific survival (CSS) were determined using multivariable and Kaplan-Meier analysis. RESULTS: Of the 473 patients, 42.5% were sarcopenic and 24.5% had hypoalbuminemia. Sarcopenia was significantly associated with shorter OS (HR=1.51, 95% CI 1.07-2.13), however, was nonsignificant in the RFS (HR = 1.33, 95% CI 0.88-2.03) and CSS (HR=1.66, 95% CI 0.96-2.87) models. Hypoalbuminemia predicted shorter OS (HR=1.76, 95% CI 1.22-2.55), RFS (HR=1.86, 95% CI 1.19-2.89), and CSS (HR=1.82, 95% CI 1.03-3.22). Patients were then stratified into low, medium, and high-risk groups based on the severity of sarcopenia and hypoalbuminemia. Risk groups demonstrated an increasing association with shorter OS (all p<0.05). Reduced RFS was observed in the medium risk-hypoalbuminemia (HR=2.18, 95% CI 1.16-4.09) and high-risk groups (HR=2.42, 95% CI 1.34-4.39). Shorter CSS was observed in the medium risk-hypoalbuminemia (HR=2.31, 95% CI 1.00-5.30) and high-risk groups (HR=2.98, 95% CI 1.34-6.61). CONCLUSION: Localized RCC patients with combined preoperative sarcopenia and hypoalbuminemia displayed a two to a three-fold reduction in OS, RFS, and CSS after nephrectomy. These data have implications for guiding prognostication and treatment election in localized RCC patients undergoing extirpative surgery.

Clinic friendly estimation of muscle composition: Preoperative linear segmentation shows overall survival correlated with muscle mass in patients with nonmetastatic renal cell carcinoma.

Purpose: Sarcopenia is associated with decreased survival and increased complications in patients with renal cell carcinoma. Readily identifying patients with low muscle composition that may experience worse outcomes or would benefit from preoperative intervention is of clinical interest. Traditional body composition analysis methods are resource intensive; therefore, linear segmentation with routine imaging has been proposed as a clinically practical alternative. This study assesses linear segmentation's prognostic utility in nonmetastatic renal cell carcinoma. Materials and Methods: A single institution retrospective analysis of patients that underwent nephrectomy for nonmetastatic renal cell carcinoma from 2005-2021 was conducted. Linear segmentation of the bilateral psoas/paraspinal muscles was completed on preoperative imaging. Total muscle area and total muscle index associations with overall survival were determined by multivariable analysis. Results: 532 (388 clear cell) patients were analyzed, with median (IQR) total muscle index of 28.6cm2/m2 (25.8-32.5) for women and 33.3cm2/m2 (29.1-36.9) for men. Low total muscle index was associated with decreased survival (HR=1.96, 95% CI 1.32-2.90, p<0.001). Graded increases in total muscle index were associated with better survival (HR=0.95, 95% CI 0.92-0.99, p=0.006). Conclusions: Linear segmentation, a clinically feasible technique to assess muscle composition, has prognostic utility in patients with localized renal cell carcinoma, allowing for incorporation of muscle composition analysis into clinical decision-making. Muscle mass determined by linear segmentation was associated with overall survival in patients with nonmetastatic renal cell carcinoma.

Data regarding covariates significantly associated with sarcopenia and varying albumin statuses in patients with renal cell carcinoma.

Poor functional, nutritional, and muscle status is a significant negative predictor for surgical and survival outcomes in patients with cancer, including renal cell carcinoma. This dataset displays results from preoperative muscle composition analysis and albumin levels in a large cohort (n = 473) of patients undergoing surgery for renal cell carcinoma. Data was obtained from retrospective review of prospectively maintained databases and retrospective image analysis. The optimal cut-point for skeletal muscle index (sarcopenia) was determined by a receiver operatic characteristic analysis to optimally stratify cohort, adjusting for BMI and sex. A threshold value of 3.5 g/dL was used to categorize normal versus low serum albumin. Patients were stratified into low risk (non-sarcopenic and normal albumin), medium risk (non-sarcopenic and low albumin, or sarcopenic and normal albumin), and high risk (sarcopenic and low albumin) groups. This data could potentially be used in future studies to determine other relationships between nutrition and musculature in renal cell carcinoma patients.

Pelvic organ prolapse recurrence after apical prolapse repair: does obesity matter?

INTRODUCTION AND HYPOTHESIS: We hypothesized obesity increases the risk of pelvic organ prolapse recurrence (POP-R) after primary apical prolapse repair. METHODS: We conducted a retrospective cohort study of 353 women who underwent primary apical prolapse surgery from 2011 to 2016. Demographic and clinical data were abstracted from medical records. Multivariable Cox proportional hazard models were used to generate hazard ratios (HR) for association between obesity (BMI ≥ 30 kg/m2) and POP-R (leading edge > 0), adjusting for potential confounders. Given the potential for outcome ascertainment bias due to differential loss to follow-up, a sensitivity analysis was performed assuming all patients with < 6 months of follow-up developed POP-R. RESULTS: Ten percent of women developed POP-R. The median follow-up time was 7 months (range 1.4, 63.9). Twenty-four percent of patients were Black and 70% were White; 37% were obese. After controlling for confounders, obese women did not have an increased risk of POP-R (aHR 1.39; 95% CI 0.67, 2.86, p = 0.38). Although only marginally statistically significant, patients who developed POP-R were more likely to be current smokers (aHR 3.48, 95% CI 1.14, 10.67; p = 0.06) or previous smokers (aHR 1.86, 95% CI 0.82, 4.24, p = 0.06) in comparison to non-smokers. Sensitivity analysis showed loss to follow-up had the potential to influence our results. CONCLUSIONS: Obesity was not a risk factor for POP-R in our cohort. Larger, prospective studies with longer postoperative follow-up time are needed to fully elucidate the relationship between obesity and POP-R.

Segmentation and Linear Measurement for Body Composition Analysis using Slice-O-Matic and Horos.

Body composition is associated with risk of disease progression and treatment complications in a variety of conditions. Therefore, quantification of skeletal muscle mass and adipose tissues on Computed Tomography (CT) and/or Magnetic Resonance Imaging (MRI) may inform surgery risk evaluation and disease prognosis. This article describes two quantification methods originally described by Mourtzakis et al. and Avrutin et al.: tissue segmentation and linear measurement of skeletal muscle. Patients' cross-sectional image at the midpoint of the third lumbar vertebra was obtained for both measurements. For segmentation, the images were imported into Slice-O-Matic and colored for skeletal muscle, intramuscular adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue. Then, surface areas of each tissue type were calculated using the tag surface area function. For linear measurements, the height and width of bilateral psoas and paraspinal muscles at the level of the third lumbar vertebra are measured and the calculation using these four values yield the estimated skeletal muscle mass. Segmentation analysis provides quantitative, comprehensive information about the patients' body composition, which can then be correlated with disease progression. However, the process is more time-consuming and requires specialized training. Linear measurements are an efficient and clinic-friendly tool for quick preoperative evaluation. However, linear measurements do not provide information on adipose tissue composition. Nonetheless, these methods have wide applications in a variety of diseases to predict surgical outcomes, risk of disease progression and inform treatment options for patients.

Sarcopenia and modified Glasgow Prognostic Score predict postsurgical outcomes in localized renal cell carcinoma.

BACKGROUND: Body composition and inflammation are gaining importance for prognostication in cancer. This study investigated the individual and combined utility of the preoperative skeletal muscle index (SMI) and the modified Glasgow Prognostic Score (mGPS) for estimating postoperative outcomes in patients with localized renal cell carcinoma (RCC) undergoing nephrectomy. METHODS: The authors performed a retrospective review of 352 patients with localized RCC. SMI was measured via computed tomography or magnetic resonance imaging. Patients met the criteria for sarcopenia by body mass index- and sex-stratified thresholds. Multivariable and Kaplan-Meier analyses of associations of sarcopenia and mGPS with overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) were performed. Variables were analyzed independently and combined into risk groups: low risk (nonsarcopenic, low mGPS), medium risk (sarcopenia only), medium risk (inflammation only), and high risk (sarcopenic, high mGPS). Receiver operating characteristic (ROC) curves were used to analyze risk groups in comparison with the Stage, Size, Grade, and Necrosis (SSIGN) score and the modified International Metastatic RCC Database Consortium (IMDC) score. RESULTS: The majority of the patients were at stage pT3 (63%), 39.5% of the patients were sarcopenic, and 19.3% had an elevated mGPS at the baseline. The median follow-up time was 30.4 months. Sarcopenia and mGPS were independently associated with worse OS (hazard ratio for sarcopenia, 1.64; P = .006; hazard ratio for mGPS, 1.72; P = .012), CSS, and RFS. Risk groups had an increasing association with worse RFS (P = .015) and CSS (P = .004) but not OS (P = .087). ROC analyses demonstrated a higher area under the curve for risk groups in comparison with the SSIGN and IMDC scores at 5 years. CONCLUSIONS: Sarcopenia and an elevated mGPS were associated with worse clinical outcomes in this study of patients with localized RCC. This has implications for preoperative prognostication and treatment decision-making. LAY SUMMARY: Kidney cancer is a disease with a wide variety of outcomes. Among patients undergoing surgical removal of the kidney for cancer that has not spread beyond the kidney, many are cured, but some experience recurrence. Physicians are seeking ways to better predict who is at risk for recurrence or death from kidney cancer. This study has evaluated body composition and markers of inflammation before surgery to predict the risk of recurrence or death after surgery. Specifically, low muscle mass and an elevated inflammation score (the modified Glasgow Prognostic Score) have been associated with an increased likelihood of recurrence of kidney cancer and death.

Implementation and evaluation of eight virtual surgical electives for medical students during the COVID-19 pandemic.

BACKGROUND: Eight novel virtual surgery electives (VSEs) were developed and implemented in April-May 2020 for medical students forced to continue their education remotely due to COVID-19. METHODS: Each VSE was 1-2 weeks long, contained specialty-specific course objectives, and included a variety of teaching modalities. Students completed a post-course survey to assess changes in their interest and understanding of the specialty. Quantitative methods were employed to analyze the results. RESULTS: Eighty-three students participated in the electives and 67 (80.7%) completed the post-course survey. Forty-six (68.7%) respondents reported "increased" or "greatly increased" interest in the course specialty completed. Survey respondents' post-course understanding of each specialty increased by a statistically significant amount (p-value = <0.0001). CONCLUSION: This initial effort demonstrated that VSEs can be an effective tool for increasing medical students' interest in and understanding of surgical specialties. They should be studied further with more rigorous methods in a larger population.

Overlapping Urological Surgeries at a Tertiary Academic Center.

OBJECTIVE: To evaluate whether the practice of procedure-time overlapping surgery (OS) is associated with inferior outcomes compared to nonoverlapping surgery (NOS) in urology, to address the paucity of data surrounding urologic surgeries to support or refute this practice. MATERIALS AND METHODS: We performed a retrospective review of all urological surgeries at a single tertiary-level academic center, Emory University Hospital, from July 2016 to July 2018. Patients who received OS were matched 1:2 to patients who had NOS. The primary outcomes were perioperative and postoperative complications and mortality. RESULTS: We reviewed 8535 urological surgeries. In-room time overlap was seen in 50.5% of cases and procedure-time overlap in 7.4%. Eleven out of the 13 attending urologists performed OS. The average time in the operating room was greater for OS by an average of 14 minutes. The average operative time was greater for OS than NOS by 11 minutes, but this did not reach statistical significance. There was no significant difference between the cohorts for rate of blood transfusions, ICU stay, need for postoperative invasive procedures, length of postoperative hospital stay, discharge location, Emergency Room visits, hospital readmission rate, 30 and 90-day rates of postoperative complications, and mortality. CONCLUSION: Procedure-time overlapping surgeries constituted a minority of urological cases. OS were associated with greater in-room time. We found no increased risk of perioperative or postoperative adverse outcomes in OS compared to matched NOS.

Quantification of body composition in renal cell carcinoma patients: Comparing computed tomography and magnetic resonance imaging measurements.

PURPOSE: Body composition measures provide valuable information for prognostication and treatment election in cancer patients. We investigated the novel use of magnetic resonance imaging (MRI) for skeletal muscle and adipose tissue cross-sectional area measurements in preoperative renal cell carcinoma (RCC) patients. MATERIALS AND METHODS: RCC patients with pre-operative CT and MRI abdominal imaging were identified. Semi-automatic segmentation measurement of skeletal muscle area (SMA), intramuscular fat area (IMFA), visceral fat area (VFA), subcutaneous fat area (SFA), linear measurements of psoas, paraspinal muscles were performed. Pearson correlation coefficients, Bland-Altman plot analyses were done. Multivariable regression analysis examined the relationship between patient characteristics and skeletal muscle. RESULTS: Image analysis was performed on 58 RCC patients with preoperative CT and MRI imaging. For segmentation measures, r = 0.99, 0.99, 0.99, and 0.98 for SMA, IMFA, VFA, SFA, respectively, and 0.96 for linear measures of skeletal muscle. Bland-Altman analysis revealed a bias toward larger CT value for SMA (1.35 %), linear muscle measures (2.79 %), and SFA (10.34 %), and toward larger MRI values for IMFA (0.75 %) and VFA (5.81 %). ECOG ≥ 1 was associated with lower skeletal muscle than ECOG 0 for all measurements. CONCLUSIONS: Strong correlation of CT and MRI cross sectional measurements of skeletal muscle and adipose tissues supports the use of axial MRI images for comprehensive measurement of body composition. This has widespread implications for body composition research and cancer patient care.

Is Continued Perioperative Antithrombotic Therapy Safe When Performing Direct Microlaryngoscopy?

OBJECTIVES/HYPOTHESIS: To evaluate whether antithrombotic status impacts the incidence of perioperative or postoperative bleeding in direct microlaryngoscopy (DML). STUDY DESIGN: Retrospective chart review. METHODS: Patients undergoing DML in a single surgeon's practice from September 2012 to September 2017 were studied. Included patients underwent DML with or without biopsy, balloon dilation, microsurgery, laser ablation, or vocal fold injection. Patients were stratified based on perioperative antithrombotic status and assessed for rates of peri- and postoperative bleeding and other complications. RESULTS: Of the 581 patients meeting inclusion criteria, 179 patients (31%) had a history of baseline antithrombotic therapy. Of these patients, 124 had perioperative continuation of their therapy. Medicated patients were older (P < .01), predominately male (P < .01), and increasingly comorbid (P < .01). Perioperative complications unrelated to bleeding occurred in 22 patients (4%), minor perioperative bleeding occurred in four patients (0.7%), and minor postoperative bleeding occurred in 12 of the 479 patients with recorded follow-up (2.5%). There were no postoperative bleeds requiring intervention or readmission, and no recorded thrombotic events during the peri- and postoperative period. There was no difference in perioperative bleeding based on baseline antithrombotic status (P = .81). Patients on baseline antithrombotic therapy were more likely to have a postoperative bleed in comparison to patients without history of antithrombotic use (P < .01). However, there were no significant differences in postoperative bleeding between patients on baseline anticoagulation who continued or ceased their medication perioperatively (P = .45). CONCLUSIONS: Perioperative continuation of antithrombotic medications appears to be safe when performing routine DML. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

Multilineage transduction of resident lung cells in vivo by AAV2/8 for α1-antitrypsin gene therapy.

In vivo gene delivery has long represented an appealing potential treatment approach for monogenic diseases such as α1-antitrypsin deficiency (AATD) but has proven challenging to achieve in practice. Alternate pseudotyping of recombinant adeno-associated virus (AAV) vectors is producing vectors with increasingly heterogeneous tropic specificity, giving researchers the ability to target numerous end-organs affected by disease. Herein, we describe sustained pulmonary transgene expression for at least 52 weeks after a single intratracheal instillation of AAV2/8 and characterize the multiple cell types transduced within the lung utilizing this approach. We demonstrate that lung-directed AAV2/8 is able to achieve therapeutic α-1 antitrypsin (AAT) protein levels within the lung epithelial lining fluid and that AAT gene delivery ameliorates the severity of experimental emphysema in mice. We find that AAV2/8 efficiently transduces hepatocytes in vivo after intratracheal administration, a finding that may have significance for AAV-based human gene therapy studies. These results support direct transgene delivery to the lung as a potential alternative approach to achieve the goal of developing a gene therapy for AATD.