Colonoscopy Utilization in Elderly Patients with Dementia: Characteristics, Complications, and Charges in a National Matched-Cohort Analysis.

BACKGROUND: It is projected that the elderly population will continue to increase. Many will develop chronic conditions such as dementia. AIMS: Our aims are to describe the utilization of colonoscopy among patients with dementia and compare outcomes in those with and without dementia. METHODS: This population-based analysis utilized the National Inpatient Sample (NIS) during 2019. Patients with dementia over the age of 60 years receiving colonoscopy were identified utilizing ICD-10 codes. Logistic regression was used for propensity score matching between the comparison groups. A Greedy one-to-one matching algorithm was utilized along with standardized mean differences to assess balance. Mcnemar test, signed rank sum, and paired t-test were used to compare the outcomes. RESULTS: Initially, 50,692 patients without dementia were compared with 4323 patients with dementia. Patients with dementia were more likely to be female, older, less likely White, had lower income, and more likely to be on Medicare. In the matched comparison (4176 in each group), complication analysis showed that patients with dementia did not have higher colonoscopy-related complications. They did have higher rates of other complications including renal/AKI (p = 0.0042), pulmonary/pneumonia (p = 0.003), cerebrovascular accidents (p = 0.0063), and sepsis (< 0.0001). Patients with dementia were also less likely to have routine discharges (< 0.0001), had longer hospital stays (< 0.0001), and higher hospital costs (< 0.0001). CONCLUSIONS: Elderly patients with dementia have similar colonoscopy-related complications as patients without dementia. However, they do have higher complications in general. The decision whether to perform colonoscopy in this patient population is multifactorial. A careful assessment of a dementia patient's history can help with this decision.

Cardiovascular implications of hypertensive autosomal dominant polycystic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is among the most common inherited kidney diseases. Hypertension is a frequent cardiovascular manifestation, especially in adults, but elevated blood pressure is also found in children and adolescents. Acknowledgment of pediatric hypertension early is critical, as it can result in serious complications long-term if left undiagnosed. OBJECTIVE: We aim to identify the influence of hypertension on cardiovascular outcomes, mainly left ventricular hypertrophy, carotid intima media thickness, and pulse wave velocity. METHODS: We performed an extensive search on Medline, Embase, CINAHL, and Web of Science databases through March 2021. Original studies with a mix of retrospective, prospective, case-control studies, cross sectional studies, and observational studies were included in the review. There was no restriction on age group. RESULTS: The preliminary search yielded 545 articles with 15 articles included after inclusion and exclusion criteria. In this meta-analysis, LVMI (SMD: 3.47 (95% CI: 0.53-6.41)) and PWV (SMD: 1.72 (95% CI: 0.08-3.36)) were found to be significantly higher in adults with ADPKD compared to non-ADPKD; however, CIMT was not found to be significantly different. Also, LVMI was observed to be significantly higher among hypertensive adults with ADPKD (n = 56) as compared to adults without ADPKD (SMD: 1.43 (95% CI: 1.08-1.79)). Fewer pediatric studies were available with heterogeneity among patient populations and results. CONCLUSIONS: Adult patients with ADPKD were found to have worse indicators of cardiovascular outcomes, including LVMI and PWV, as compared to non-ADPKD. This study demonstrates the importance of identifying and managing hypertension, especially early, in this population. Further research, particularly in younger patients, is necessary to further elucidate the relationship between hypertension in patients with ADPKD and cardiovascular disease. REGISTRATION NUMBER: PROSPERO REGISTRATION: 343,013.

Sarcopenia and systemic inflammation are associated with decreased survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

BACKGROUND: This study was aimed at assessing the associations of sarcopenia, muscle density, adiposity, and inflammation with overall survival (OS) after cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma. METHODS: In all, 158 patients undergoing CN from 2001 to 2014 had digitized preoperative imaging for tissue segmentation via Slice-O-Matic software (version 5.0) at the mid-L3 level. The skeletal muscle index was calculated with the skeletal muscle area (cm2 ) normalized for height (m2 ), and the skeletal muscle density (SMD) was calculated with average Hounsfield units. Adiposity was measured with the cross-sectional area (cm2 ) of visceral, subcutaneous, and intramuscular adiposity compartments and was similarly normalized for height. The average fat density was obtained in Hounsfield units. OS was estimated with the Kaplan-Meier method. Associations between body composition, inflammation metrics, and relevant clinicopathology and OS were assessed with univariable and multivariate Cox analyses. RESULTS: Seventy-six of the 158 patients (48%) were sarcopenic. Sarcopenia was associated with elevated neutrophil to lymphocyte ratios (NLRs; P = .02), increased age (P = .001), lower body mass indices (P = .009), greater modified Motzer scores (P = .019), and lower SMD (P = .006). The median OS was 15.0 and 29.4 months for sarcopenic and nonsarcopenic patients, respectively (P = .04). Elevated inflammation (NLR or C-reactive protein), in addition to sarcopenia, was independently associated with OS, with an elevated NLR ≥ 3.5 and sarcopenia associated with the poorest OS at 10.2 months. No associations were observed between measurements of muscle density or adiposity and OS. CONCLUSIONS: Sarcopenia and measures of high systemic inflammation are additively associated with inferior OS after CN and may be of use in preoperative risk stratification. LAY SUMMARY: Body composition and sarcopenia (a deficiency in skeletal musculature) have been shown to affect outcomes in cancer. We found that sarcopenic patients had poor survival in comparison with nonsarcopenic patients in the setting of metastatic renal cell carcinoma (mRCC). Patients with both elevated inflammation and sarcopenia had the poorest survival. Sarcopenia is an objective measure of nutrition that can assist in therapeutic counseling and decision-making for individualized treatment in mRCC.

Outcomes in Patients with Renal Cell Carcinoma Undergoing Inferior Vena Cava Ligation without Reconstruction versus Thrombectomy: A Retrospective, Case Controlled Study.

PURPOSE: Radical nephrectomy with tumor thrombectomy is considered standard of care in patients with renal cell carcinoma. However, surgical ligation and interruption of the inferior vena cava is sometimes necessary when the tumor thrombus invades the inferior vena cava wall. This study assesses the outcomes in patients with renal cell carcinoma undergoing inferior vena cava ligation compared to inferior vena cava thrombectomy. MATERIALS AND METHODS: We conducted a case controlled, retrospective study at a high volume single-center institution. All patients with renal cell carcinoma who underwent ligation without reconstruction were matched with patients undergoing thrombectomy in a 1:2 ratio based on preoperative renal function, renal cell carcinoma stage and intraoperative thrombus level. Endpoints were complications, change in renal function and mortality. RESULTS: A total of 26 patients with renal cell carcinoma who underwent inferior vena cava ligation between 2005 and 2019 were matched with 52 patients who underwent inferior vena cava thrombectomy in the same time period. When compared to thrombectomy, patients undergoing ligation had higher 90-day readmission rate (19% vs 4%, p=0.025). The ligation group also had a higher postoperative complication rate (73% vs 39%, p=0.004) and higher rates of lymphedema (23% vs 8%, p=0.055). However, by 1-month followup the rate of persistent overall and major complications for both ligation and thrombectomy groups were comparable at 49% vs 31% (p=0.497) ad 8% vs 8% (p=1.000), respectively. Importantly, at 18-month followup, mean estimated glomerular filtration rate declines were similar between ligation group (8.5 ml/min/1.73 m2) and thrombectomy group (9.9 ml/min/1.73 m2; p=0.834). Differences in cancer-specific mortality (p=0.993) and all-cause mortality (p=0.756) were also not statistically significant. CONCLUSIONS: The outcomes of inferior vena cava ligation compared to inferior vena cava thrombectomy for renal cell carcinoma are similar. Patients with inferior vena cava ligation initially face a more complicated postoperative course but in the longer term have similar renal function recovery, complication rates and survival.

A randomized, controlled trial for transurethral treatment of bladder tumors using PlasmaButton vaporization electrode or monopolar loop electrocautery.

INTRODUCTION: The use of an electrocautery device (monopolar loop) for patients undergoing transurethral resection of bladder tumors (TURBT) is standard of care. The aim of this study is to establish non-inferiority of complication rates for a bipolar energy device, the PK PlasmaButton (PK Button), when compared to the monopolar loop. MATERIALS AND METHODS: Seventy-eight subjects (41 monopolar loop and 37 PK Button), were enrolled in a single-center, prospective, randomized study with cystoscopically detected bladder tumors that were judged endoscopically resectable with only one trip into the operating room. Intra and postoperative data on complication rates, operative time, catheterization time and disease recurrence rates at 3 month follow up were collected. RESULTS: Overall complication rates after TURBT with the monopolar loop or PK Button were similar, (56% versus 38% respectively, p = 0.107), however there were more bladder perforations in the monopolar loop arm compared to the PK Button arm (12.2% versus 0%, respectively, p = 0.028). There was no difference in overall operative time (p = 0.170), catheterization time (p = 0.709) and disease recurrence (p = 0.199). CONCLUSION: The results of this study demonstrated no difference between the monopolar loop and PK Button in regard to overall complications; however, there was a higher rate of bladder perforation with monopolar TURBT. PK Button vaporization for bladder tumors represents a promising alternative to traditional monopolar TURBT without compromising short term (3 month) cancer recurrence rates.

COVID-19 and Its Sequelae Masquerading as Gastrointestinal Ailments: A Report of Gastroesophageal Reflux Disease (GERD) and Review of Recent Cases.

Coronavirus disease 2019 (COVID-19) predominantly causes respiratory symptoms. However, a rare segment of patients recovering from COVID-19 may develop gastrointestinal (GI) symptoms. We describe a case of a female who presented with symptoms suggestive of refractory gastroesophageal reflux disease (GERD) for 18 months following COVID-19 infection. Her symptoms included epigastric and chest pain, coughing, and vomiting. Upper endoscopy and 24-hour pH monitoring were negative. Following hospital admission due to worsening symptoms, she was diagnosed with chronic pulmonary embolism (PE) presumed to be related to COVID-19. Her reflux symptoms resolved within two days of the initiation of anticoagulation. Our findings suggest that chronic PE should be considered in patients presenting with GERD refractory to treatment following COVID-19 infection. Generally, as COVID-19 and its sequelae may masquerade as GI conditions, they should be on the differential diagnosis, especially in the post-pandemic era when routine testing has significantly declined.

SMARCA4-Deficient Undifferentiated Esophageal Carcinoma: A Clinical Case Series and Literature Review.

PURPOSE: Undifferentiated carcinoma of the esophagus (UEC) is a rare malignancy. Deficiency in SMARCA genes, critical for chromatin regulation, has been observed in cases of UEC. Research in UEC is sparse, however, and we present a case series along with a comprehensive review of the literature. CASE SERIES: Case 1 is a 49-year-old female with abdominal pain and dysphagia and esophagogastroduodenoscopy (EGD) showing a friable mass at the gastroesophageal (GE) junction. Biopsies showed a poorly differentiated neoplasm and immunohistochemistry showed loss for SMARCA4. With metastatic disease, she agreed to undergo palliative chemotherapy and radiation, passing away at 4 months. Case 2 is an 88-year-old male with dysphagia, nausea, vomiting, and distal esophageal mass with biopsy showing a malignancy with loss of SMARCA4 expression. Due to extensive metastases, he was counseled on hospice care. Case 3 is a 53-year-old male with extensive alcohol and smoking history presenting with hematemesis, passing away shortly. Posthumous histopathology consistent with undifferentiated SMARCA4-deficient carcinoma of the esophagus. Results of the literature review indicate a predilection towards males (75.0%) and a variable age range (39-88 years). Majority (76.2%) reported with a distal esophagus location. Metastatic disease was common at initial presentation. Median survival was 2.60 months. Some were managed with chemotherapy and radiation. CONCLUSIONS: Research in SMARCA-deficient UEC is very limited. It is more common in men, age is variable, and associated with Barret's esophagus. Further research is necessary to better understand it and to establish treatment guidelines; however, it is clear that SMARCA4-deficient UEC carries a significantly poor prognosis.

CAG Repeat Instability in the Peripheral and Central Nervous System of Transgenic Huntington's Disease Monkeys.

Huntington's Disease (HD) is an autosomal dominant disease that results in severe neurodegeneration with no cure. HD is caused by the expanded CAG trinucleotide repeat (TNR) on the Huntingtin gene (HTT). Although the somatic and germline expansion of the CAG repeats has been well-documented, the underlying mechanisms had not been fully delineated. Increased CAG repeat length is associated with a more severe phenotype, greater TNR instability, and earlier age of onset. The direct relationship between CAG repeat length and molecular pathogenesis makes TNR instability a useful measure of symptom severity and tissue susceptibility. Thus, we examined the tissue-specific TNR instability of transgenic nonhuman primate models of Huntington's disease. Our data show a similar profile of CAG repeat expansion in both rHD1 and rHD7, where high instability was observed in testis, liver, caudate, and putamen. CAG repeat expansion was observed in all tissue samples, and tissue- and CAG repeat size-dependent expansion was observed. Correlation analysis of CAG repeat expansion and the gene expression profile of four genes in different tissues, clusterin (CLU), transferrin (TF), ribosomal protein lateral stalk subunit P1 (RPLP1), and ribosomal protein L13a (RPL13A), showed a strong correlation with CAG repeat instability. Overall, our data, along with previously published studies, can be used for studying the biology of CAG repeat instability and identifying new therapeutic targets.

Anti-factor H antibody and its role in atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) an important form of a thrombotic microangiopathy (TMA) that can frequently lead to acute kidney injury (AKI). An important subset of aHUS is the anti-factor H associated aHUS. This variant of aHUS can occur due to deletion of the complement factor H genes, CFHR1 and CFHR3, along with the presence of anti-factor H antibodies. However, it is a point of interest to note that not all patients with anti-factor H associated aHUS have a CFHR1/R3 deletion. Factor-H has a vital role in the regulation of the complement system, specifically the alternate pathway. Therefore, dysregulation of the complement system can lead to inflammatory or autoimmune diseases. Patients with this disease respond well to treatment with plasma exchange therapy along with Eculizumab and immunosuppressant therapy. Anti-factor H antibody associated aHUS has a certain genetic predilection therefore there is focus on further advancements in the diagnosis and management of this disease. In this article we discuss the baseline characteristics of patients with anti-factor H associated aHUS, their triggers, various treatment modalities and future perspectives.

Low free testosterone is associated with increased mortality in frail surgical patients.

BACKGROUND: Preoperative frailty has been associated with adverse postoperative outcomes. Additionally, low testosterone has been associated with physical frailty and cognitive decline. However, the impact of simultaneous frailty and low testosterone on surgical outcomes is understudied. METHODS: Preoperative frailty status and testosterone levels were obtained in patients undergoing a diverse range of surgical procedures. Preoperative frailty was evaluated independently and in combination with testosterone through the creation of composite risk groups. Relationships between preoperative frailty and composite risk groups with overall survival were determined using Kaplan-Meier and logistic regression analyses. Bivariate analysis was used to determine the associations between frailty and testosterone status on postoperative complications, length of hospital stay, and readmission rates. RESULTS: Median age of the cohort was 63 years, and the median follow-up time was 105 weeks. Thirty-one patients (23%) were frail, and 36 (27%) had low free testosterone. Bivariate analysis demonstrated a statistically significant relationship between preoperative frailty and overall survival (P = .044). In multivariate analysis, coexisting frailty and low free testosterone were significantly associated with decreased overall survival (hazard ratio 4.93, 95% confidence interval, 1.68-14.46, P = .004). CONCLUSION: We observed preoperative frailty, both independently and in combination with low free testosterone levels, to be significantly associated with decreased overall survival across various surgical procedures. Personalizing the surgical risk assessment through the incorporation of preoperative frailty and testosterone status may serve to improve the prognostication of patients undergoing major surgery.

Association of grit and overall survival in patients undergoing nephrectomy for renal cell carcinoma.

Background: Quantifying grit with the Short Grit Scale (Grit-S) has shown ability to predict success in various academic and professional domains. Grit has yet to be analyzed in patients with cancer. Methods: This study is a longitudinal analysis of prospectively distributed Grit-S surveys to patients undergoing radical or partial nephrectomy. Patients who completed a preoperative Grit-S survey with confirmed renal cell carcinoma (RCC) were included in the analysis. The relationship between preoperative grit scores and overall survival (OS) was determined using Cox proportional-hazard models and Kaplan-Meier analysis. Results: A total of 323 patients with RCC that completed the Grit-S survey prior to nephrectomy were included in the study. Median Grit score was 3.9. Most patients were male (67.5%), White (69.3%), and greater than 60 years old (57.0%) with a median age of 62 at the time of surgery. Patients scoring above or below the median grit score had similar baseline characteristics. As a binary variable, lower preoperative grit was significantly associated with shorter OS [hazard ratio (HR) =2.02, 95% confidence interval (CI): 1.12-3.63, P=0.019] on multivariable analysis. Unit changes in grit were not significantly associated with OS (HR =0.77, 95% CI: 0.53-1.14, P=0.193). Conclusions: Lower grit scores may predict decreased OS in RCC patients undergoing nephrectomy. The Grit-S survey may have utility in preoperative evaluation. Further research assessing grit in other malignancies and how to psychologically optimize patients prior to surgery are needed.

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.

Transplant Radical Nephrectomy and Transplant Radical Nephroureterectomy for Renal Cancer: Postoperative and Survival Outcomes.

BACKGROUND The treatment of complex tumors in non-functioning renal transplants requiring surgical extirpation is challenging. Here, we report the largest series of patients who underwent transplant radical nephrectomy for renal cell carcinoma (RCC) and transplant radical nephroureterectomy for urothelial cell carcinoma (UCC) in their transplanted kidneys. MATERIAL AND METHODS From 2004 to 2018, 10 patients underwent transplant radical nephrectomy (7 patients) and nephroureterectomy (3 patients). Retrospective analyses, in terms of complications, oncological recurrence, and survival, of peri-operative and long-term outcomes, were performed. RESULTS Out of the 10 patients, 7 had RCC and 3 had UCC. No intraoperative mortality occurred. Three patients presented with Clavien-Dindo grade IIIa or greater within 30 days of surgery. Two patients died within 60 days of surgery, both due to vascular events: one due to myocardial infarction and one due to stroke. Two other patients died: one after 2.9 years, due to myocardial infarction, and the other after 6 years, due to unknown reasons. At the 7-year follow-up, there was a 60% overall survival rate. For all patients, average survival post-nephrectomy was approximately 4.5 years, including the 6 living patients and 4 deceased patients. Importantly, there was no observed cancer recurrence. CONCLUSIONS This study reports outcomes of the largest series of transplant radical nephrectomy and nephroureterectomy for malignancies of renal allografts. In the optimized setting, extirpative surgeries appear safe, with favorable long-term oncological and survival outcomes.

The immunosuppressive phenotype of tumor-infiltrating neutrophils is associated with obesity in kidney cancer patients.

Infiltrating tumor neutrophils and myeloid-derived suppressor cells represent major populations in the tumor microenvironment that contribute to tumor progression. However, the phenotype of circulating and tumor-associated neutrophils, and the impact of cancer patients' metabolic state on neutrophil function need further characterization. Here we show that in kidney cancer patients, circulating neutrophils display an altered immature-like phenotype, and an activated/primed metabolic state. Circulating immature-like neutrophils acquire an activated phenotype upon migration into the tumor tissue, characterized by high expression of the immunosuppressive enzyme arginase-1, and active granule release. Interestingly, obesity and adipose tissue distribution were significantly associated with this activated phenotype of neutrophils, including the release of arginase-1 in the tumor tissue. These results provide a possible functional relationship between the metabolic status of the patients and disease progression, through an active immunosuppressive role of neutrophils within the kidney tumor microenvironment.

Outcome of Encephalitis in Pediatric Intensive Care Unit.

OBJECTIVE: To review pathogens, morbidity and mortality in pediatric intensive care unit (PICU) patients with viral and infectious encephalitis. METHODS: Retrospective chart review of all patients with encephalitis admitted to the PICU between 2002 and 2014 was done. RESULTS: Encephalitis (n = 46) accounted for 2.7 % of PICU admissions, but 11.8 % PICU mortality over a 12-y period. A microorganism (primarily virus) was identified in 59 % of encephalitis patients in the PICU. Enteroviruses and herpes viruses were isolated from the cerebrospinal fluid (CSF). Respiratory viruses [such as respiratory syncytial virus (RSV) and influenza viruses] and enteric viruses (such as rotavirus and norovirus) were obtained in the nasopharyngeal aspirate and stool respectively, but undetectable from the CSF. More than one-fourth patients with encephalitis died in the PICU. Boys accounted for 85 % of nonsurvivors and 52 % survivors (p = 0.038). Mechanical ventilation, inotrope, intravenous immunoglobulin (IVIG) and corticosteroid usage were significantly higher among non-survivors (p 0.001-0.044). Binomial logistic regression showed that patients who received corticosteroid had a lower chance of survival than those who did not after adjusting for gender, IVIG and mechanical ventilation (adjusted odd ratio = 0.071, 95 % CI 0.006-0.881; p 0.039). Eighteen (55 %) of the survivors had moderate-to-severe neurodevelopmental impairments. CONCLUSIONS: Encephalitis is associated with significant mortality despite intensive care. Over 25 % case died and 55 % of survivors had moderate-to-severe neurodevelopmental impairments. There appeared to be no emerging outbreaks of encephalitis during the 15-y study period.