Publications

BACKGROUND: Survival of Wilms tumor (WT) is > 90% in high-resource settings but < 30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in low-resource settings, but a local control strategy is crucial to improving outcomes.

OBJECTIVE: Provide resource-sensitive recommendations for the surgical management of WT.

METHODS: We performed a systematic review of PubMed and EMBASE through July 7, 2020, and used the GRADE approach to assess evidence and recommendations.

RECOMMENDATIONS: Initiation of treatment should be expedited, and surgery should be done in a high-volume setting. Cross-sectional imaging should be done to optimize preoperative planning. For patients with typical clinical features of WT, biopsy should not be done before chemotherapy, and neoadjuvant chemotherapy should precede surgical resection. Also, resection should include a large transperitoneal laparotomy, adequate lymph node sampling, and documentation of staging findings. For WT with tumor thrombus in the inferior vena cava, neoadjuvant chemotherapy should be given before en bloc resection of the tumor and thrombus and evaluation for viable tumor thrombus. For those with bilateral WT, neoadjuvant chemotherapy should be given for 6-12 weeks. Neither routine use of complex hilar control techniques during nephron-sparing surgery nor nephron-sparing resection for unilateral WT with a normal contralateral kidney is recommended. When indicated, postoperative radiotherapy should be administered within 14 days of surgery. Post-chemotherapy pulmonary oligometastasis should be resected when feasible, if local protocols allow omission of whole-lung irradiation in patients with nonanaplastic histology stage IV WT with pulmonary metastasis without evidence of extrapulmonary metastasis.

CONCLUSION: We provide evidence-based recommendations for the surgical management of WT, considering the benefits/risks associated with limited-resource settings.

Collagen XI plays a role in nucleating collagen fibrils and in controlling fibril diameter. The aim of this research was to elucidate the role that collagen XI plays in corneal fibrillogenesis during development and following injury. The temporal and spatial expression of collagen XI was evaluated in C57BL/6 wild-type mice. For wound-healing studies in adult mice, stromal injuries were created using techniques that avoid caustic chemicals. The temporal expression and spatial localization of collagen XI was studied following injury in a Col11a1 inducible knockout mouse model. We found that collagen XI expression occurs during early maturation and is upregulated after stromal injury in areas of regeneration and remodeling. Abnormal fibrillogenesis with new fibrils of heterogeneous size and shape occurs after injury in a decreased collagen XI matrix. In conclusion, collagen XI is expressed in the stroma during development and following injury in adults, and is a regulator of collagen fibrillogenesis in regenerating corneal tissue.

BACKGROUND: Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide.

METHODS: A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000-2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models.

RESULTS: Eight studies met inclusion criteria (n = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06-0.36]). Liver metastasis (odds ratio 2.85 [1.49-5.47]) and gender (male 0.58 [0.34-0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03-4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32-1.66]). Notably, there was no standard prophylactic octreotide strategy used.

CONCLUSIONS: Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC.

PURPOSE: The aim of this study was to determine the prevalence of any and chronic tinnitus among female and male individuals from varied Hispanic/Latino backgrounds and to estimate associations between risk factors for chronic tinnitus.

METHOD: Our analysis used cross-sectional baseline data collected from 2008 to 2011 from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Prevalence estimates and multivariable logistic regression were conducted using survey methodology. Participants included 15,768 adults (8,229 women and 7,539 men) aged 18-76 years. The primary outcome of interest was chronic tinnitus, defined as self-reported tinnitus lasting ≥ 5 min at a time and at least once per week. We hypothesized that after adjusting for covariates, the risk factors of depressed and anxious symptoms, smoking history, hypertension, and noise exposure history would be associated with higher odds of chronic tinnitus.

RESULTS: Unstratified prevalence for any tinnitus was 32.9%, and for chronic tinnitus, it was 12.1%. Sex-stratified results demonstrated that 2,995 female individuals (36.4%) and 2,187 male individuals (29.0%) reported any tinnitus, and of these, 1,043 female individuals (12.7%) and 870 male individuals (11.5%) reported chronic tinnitus. In the fully adjusted model, depressed and anxious symptoms as well as recreational noise exposure were associated with higher odds of chronic tinnitus in female individuals (odds ratios [ORs] = 1.06, confidence interval [CI; 1.04, 1.07]; 1.02, CI [1.01, 1.04]; and 1.40, CI [1.20, 1.62]) and in male individuals (ORs = 1.06, CI [1.03, 1.08]; 1.05, CI [1.02, 1.08]; and 1.30, CI [1.05, 1.65]). Current smoking was a risk factor for chronic tinnitus in male individuals (OR = 1.53, CI [1.16, 2.02]).

CONCLUSIONS: Prevalence of any and chronic tinnitus in the HCHS/SOL baseline cohort is higher than that reported in previous studies, particularly among female individuals. Understanding risk factors associated with tinnitus is important for the development of culturally and linguistically appropriate public health programs that consider sex differences and promote lifestyle modifications known to lower the odds of experiencing tinnitus.

Atrial fibrillation (AF), the most common abnormal heart rhythm, is a major cause for stroke. Aging is a significant risk factor for AF; however, specific ionic pathways that can elucidate how aging leads to AF remain elusive. We used young and old wild-type and PKC epsilon- (PKCϵ) knockout mice, whole animal, and cellular electrophysiology, as well as whole heart, and cellular imaging to investigate how aging leads to the aberrant functioning of a potassium current, and consequently to AF facilitation. Our experiments showed that knocking out PKCϵ abrogates the effects of aging on AF by preventing the development of a constitutively active acetylcholine sensitive inward rectifier potassium current (IKACh). Moreover, blocking this abnormal current in the old heart reduces AF inducibility. Our studies demonstrate that in the aging heart, IKACh is constitutively active in a PKCϵ-dependent manner, contributing to the perpetuation of AF.

BACKGROUND: Dolutegravir (DTG) is widely used for the management of naïve and treatment-experienced HIV-infected patients. Low-level viremia (LLV) is common in patients receiving nonnucleoside reverse transcriptase inhibitor- and protease inhibitor-containing regimens. However, the incidence of LLV associated with DTG-containing regimen is not well known.

OBJECTIVE: The objective of this study was to assess the virological response associated with DTG-containing regimens and explored frequencies of LLV and risk factors for the same.

METHODS: We performed a retrospective cohort study of HIV-infected patients receiving generic DTG-containing regimen from February 2017 to July 2019. All adult patients (≥18 years), who completed at least the first follow-up after initiating treatment, were included in this study. LLV was defined as plasma viral load between 20 and 200 copies/ml.

RESULTS: A total of 597 patients started DTG-containing regimen during the study period, of which 522 patients met the inclusion criteria. The study patients were categorized into five groups: naïve (n = 86), first-line failure (n = 32), second-line failure (n = 53), switch (n = 325), and HIV-2 (n = 26). Complete virological suppression at 6, 12, and 18 months was achieved in 78.5%, 81.1%, and 70.9% of the patients, respectively. Furthermore, 17.9%, 12.9%, and 23.3% of the patients had LLV at 6, 12, and 18 months, respectively. Persistent LLV was found in 2.9% of the patients. Overall, DTG was well tolerated and was discontinued in only three patients due to neuropsychiatric side effects.

CONCLUSION: DTG is well tolerated and effective in suppressing HIV across all antiretroviral treatment categories. The rate of persistent LLV is low in DTG-containing therapy.

BACKGROUND: Timed barium swallow (TBS) assesses esophageal emptying before and after therapy in patients with achalasia. Our aim was to compare the accuracy of percent change in barium height with traditional absolute cutoff of <5 cm on post-treatment TBS.

MATERIALS AND METHODS: Consecutive patients with treatment naïve achalasia treated with either PD, HM, or POEM between 1/2012 and 7/2017 were eligible for inclusion. The accuracy of percent change in pre- and post-treatment barium height at 5 minutes versus an absolute <5 cm cutoff for assessing treatment response was assessed using the receiver operating curve analysis (ROC).

RESULTS: Eighty-one patients met the inclusion criteria. The median percent change in barium heights at five minutes in patients who did not improve was 6 percent increase (n = 10; mean 10.6) versus 78 percent decrease (n = 71; mean 64) in patients who improved (P = 0.0001). The AUC for percent change in TBS 5 minutes height was 76% (95% CI 48% to 90%), and a 3% decrease from baseline as a cutoff had a sensitivity of 60% and specificity of 99%. The AUC for post-treatment TBS 5 minutes height was 79% (95% CI 53% to 91%), and the 5 cm cutoff had a sensitivity of 70% and specificity of 75%.

CONCLUSIONS: The results show that 3% percent improvement in pre- and post-treatment barium height at 5 minutes rather than absolute cutoff value of <5 cm on post-treatment TBS is a better indicator of treatment success in achalasia patients. These findings indicate the need for reassessment of tools to identify treatment response.

BACKGROUND: The vertical rectus abdominis myocutaneous (VRAM) flap has been frequently used for perineal reconstruction given the high potential for wound complications associated with direct closure of this area. However, the relationship between defect size and postoperative complications remains undefined.

METHODS: A retrospective chart review of the last 20 years for VRAM flaps was performed. Defect size, age, body mass index (BMI), cause of defect, sex, radiation, and flap donor laterality were recorded. Complications of infection, partial flap loss, total flap loss, minor wounds, treated nonoperatively, and major wound, which required reoperation, were analyzed with respect to defect size. Descriptive statistics were used to summarize the demographic and clinical characteristics of the included patients. Associations were assessed using binary logistic regression analysis, and difference in means for compared groups was assessed using the independent samples t test. P values were set at 5% for all comparisons.

RESULTS: There were 65 patients with VRAM flaps identified during the review period. Mean defect size was 204.71 cm2. Mean age was 63.97, and mean BMI was 27.18. History of prior radiation was noted in 90.77% of patients (n = 59). When adjusted for age and BMI, mean defect area was significantly different for patients with minor or major wounds. Larger perineal defects were associated with increased risk of major wound complications (odds ratio, 1.012; 95% confidence interval, 1.003-1.022).

CONCLUSIONS: The vertical rectus abdominis flap has been a workhorse flap for perineal reconstruction. Defect size does not affect risk of partial flap necrosis, complete flap loss, infection, abdominal fascial dehiscence, ventral hernia, or seroma, which supports the utility of VRAM flap for perineal reconstruction. Larger perineal defects are associated with increased risk for major wound complications, which required reoperation, regardless of age or BMI. Future studies should be performed to determine if there is a maximum defect size cutoff that limits the utility of VRAM flap reconstruction or to develop a predictive model to assess the risk of major wound complications based on defect size.

OBJECTIVES: Reports of medical student mentorship prevalence range between 26% and 77%. This broad range likely reflects the tendencies of studies to focus on specific populations of medical students. There is little consensus about the characteristics of mentoring relationships among medical students. The primary goal of this study was to determine the reported prevalence of mentorship among medical students in the United States. The secondary goals were to assess the desired qualities of and barriers to successful mentoring from a medical student perspective.

METHODS: A cross-sectional online survey was administered via Qualtrics to all medical students at participating accredited medical schools from July 2018 to March 2019. The questionnaire contained a subsection of questions that assessed the existence of mentoring, facilitators, and barriers in finding a mentor, and the desired qualities of a successful mentor.

RESULTS: With a 94% completion rate, 369 (69%) of 532 medical students reported having a mentor. Adjusted analysis showed that fourth-year medical students were significantly more likely to have a mentor compared with first-year (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.49-4.73, P = 0.001), second-year (OR 2.07, 95% CI 1.14-3.76, P = 0.016), and third-year medical students (OR 2.16, 95% CI 1.2-3.90, P = 0.011). Compassion (64%) was the most commonly reported quality in a successful mentoring relationship. Lack of time from mentor (75%) was the most commonly reported barrier.

CONCLUSIONS: This study may serve as a guide to fostering more supportive mentoring relationships. Each mentoring relationship should be tailored to the needs of the mentee, however.