How I Do It: ERAS protocol featuring erector spinae plane block for percutaneous nephrolithotomy.

Percutaneous nephrolithotomy (PCNL) is the gold-standard treatment for large and complex renal stones. Though associated with higher stone-free rates compared to other minimally invasive stone procedures, this comes at the expense of increased morbidity including postoperative pain and discomfort. We describe our enhanced recovery after surgery (ERAS) protocol for PCNL with emphasis on the use of erector spinae plane blocks to improve patient satisfaction and reduce postoperative opioid use and bother.

Contemporary diagnosis and management of pelvi-ureteric junction obstruction.

Pelvi-ureteric junction obstruction (PUJO) is defined as a functionally significant impairment of the flow of urine from the kidney's renal pelvis into the proximal ureter. Symptomatically, the patient may experience flank pain, recurrent infections, stone formation, and impairment of renal function. Although many cases of intrinsic PUJO are diagnosed at birth, a minority of patients may present in adulthood with previously silent disease or develop secondary PUJO to other causes. PUJO is therefore broadly categorised into both primary and secondary PUJO. A wide array of diagnostic scans and tests are available to aid in diagnosing and monitoring patients with PUJO. In patients with compromised renal function or symptomatic PUJO that require intervention, minimally invasive techniques are the 'gold standard' for surgical intervention. This review will detail the endoscopic, laparoscopic, and robotic options available to the urologist practicing in 2021, including the use of autografts and other emerging technologies.

Evaluating the association between food insecurity and risk of nephrolithiasis: an analysis of the National Health and Nutrition Examination Survey.

PURPOSE: This study aimed to investigate the relationship between self-reported food security and kidney stone formation. METHODS: Data were collected from the National Health and Nutrition Examination Survey (NHANES), a database representative of the United States population. Food security status was assessed using the US Household Food Security Survey Module: Six-Item Short Form. Characteristics of patients were compared using the Chi-square test and the student t-test. Multivariate logistic regression was performed using a multi-model approach. RESULTS: We analyzed 6,800 NHANES survey respondents. 37.2% of respondents were categorized as having "low food security" (scores 2-4) and 24.0% having "very low food security" (scores 5-6). 8.4% of respondents had a history of kidney stones. We found that people with very low food security had a 42% increased likelihood of developing kidney stones compared to those with high or marginal food security, after controlling for race, age, and comorbidities (OR 1.42; 95% CI 1.01-1.99). Between the different food security groups, no significant differences were observed in age, race/ethnicity, body mass index, gout history, osteoporosis history, or coronary artery disease history. Lower food security was associated with slightly younger age (< 1 year difference, p = 0.001), higher poverty-income ratio (p = 0.001), and many comorbidities, including kidney stones (p = 0.007). CONCLUSION: Our study provides evidence for an association between food access and the risk of kidney stone disease. Given these findings, food insecurity should be investigated as a modifiable risk factor for the development of kidney stone disease.

Bioactivites of Penicillium citrinum isolated from a medicinal plant Swertia chirayita.

Endophytes associated with plants have the property to produce active biomolecules with their possible applications in agro-industrial sectors. This study provides a project work on analyzing various activities of fungal endophytes isolated from Swertia chirayita of Sikkim Himalayan region. Among several fungal endophytes screened, isolate UTCRF6 was found most active with the secretion of enzymes protease, cellulase, amylase and chitinase, as well as other metabolites Indoleacetic acid and siderophores. This endophyte was found active in restricting the growth of phyto-pathogens, including strains of Fusarium solani, Colletotrichum gloeosporioides, Alternaria alternata, Pestalotiopsis theae and Sclerotinia sclerotiorum. Morphological and molecular studies of this endophytic fungus showed similarity with Penicillium citrinum.

Frailty as predictor of complications in patients undergoing percutaneous nephrolithotomy (PCNL).

INTRODUCTION & OBJECTIVE: Surgical complications are difficult to predict, despite existing tools. Frailty phenotype has shown promise estimating postoperative risk among the elderly. We evaluate the use of frailty as a predictive tool on patients undergoing percutaneous renal surgery. METHODS: Frailty was prospectively analyzed using the Hopkins Frailty Index, consisting of 5 components yielding an additive score: patients categorized not frail, intermediate, or severely frail. Primary outcomes were complications during admission and 30-day complication rate. Secondary outcomes included overall hospital length of stay (LOS) and discharge location. RESULTS: A total of 100 patients recruited, of whom five excluded as they did not need the procedure. A total of 95 patients analyzed; 69, 10, and 16 patients were not frail, intermediate, and severely frail, respectively. There were no differences in blood loss, number of dilations, presence of a staghorn calculus, laterality, or location of dilation. Severely frail patients were likely to be older and have a higher American Society of Anesthesiologists score and Charlson comorbidity index. Patients of intermediate or severe frailty were more likely to exhibit postoperative fevers, bacteremia, sepsis, and require ICU admissions (P < 0.05). Frail patients had a longer LOS (P < 0.001) and tended to require skilled assistance when discharge (p < 0.0001). CONCLUSIONS: Frailty assessment appears useful stratifying those at risk of extended hospitalization, septic complications, and need for assistance following percutaneous renal surgery. Risks of sepsis, bacteremia, and post-operative hemorrhage may be higher in frail individuals. Preoperative assessment of frailty phenotype may give insight into treatment decisions and represent a modifiable marker allowing future trials exploring the concept of "prehabilitation".

The novel BH3 α-helix mimetic JY-1-106 induces apoptosis in a subset of cancer cells (lung cancer, colon cancer and mesothelioma) by disrupting Bcl-xL and Mcl-1 protein-protein interactions with Bak.

BACKGROUND: It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-2/Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. We designed the BH3 α-helix mimetic JY-1-106 to engage the hydrophobic BH3-binding grooves on the surfaces of both Bcl-xL and Mcl-1. METHODS: JY-1-106-protein complexes were studied using molecular dynamics (MD) simulations and the SILCS methodology. We have evaluated the in vitro effects of JY-1-106 by using a fluorescence polarization (FP) assay, an XTT assay, apoptosis assays, and immunoprecipitation and western-blot assays. A preclinical human cancer xenograft model was used to test the efficacy of JY-1-106 in vivo. RESULTS: MD and SILCS simulations of the JY-1-106-protein complexes indicated the importance of the aliphatic side chains of JY-1-106 to binding and successfully predicted the improved affinity of the ligand for Bcl-xL over Mcl-1. Ligand binding affinities were measured via an FP assay using a fluorescently labeled Bak-BH3 peptide in vitro. Apoptosis induction via JY-1-106 was evidenced by TUNEL assay and PARP cleavage as well as by Bax-Bax dimerization. Release of multi-domain Bak from its inhibitory binding to Bcl-2/Bcl-xL and Mcl-1 using JY-1-106 was detected via immunoprecipitation (IP) western blotting.At the cellular level, we compared the growth proliferation IC50s of JY-1-106 and ABT-737 in multiple cancer cell lines with various Bcl-xL and Mcl-1 expression levels. JY-1-106 effectively induced cell death regardless of the Mcl-1 expression level in ABT-737 resistant solid tumor cells, whilst toxicity toward normal human endothelial cells was limited. Furthermore, synergistic effects were observed in A549 cells using a combination of JY-1-106 and multiple chemotherapeutic agents. We also observed that JY-1-106 was a very effective agent in inducing apoptosis in metabolically stressed tumors. Finally, JY-1-106 was evaluated in a tumor-bearing nude mouse model, and was found to effectively repress tumor growth. Strong TUNEL signals in the tumor cells demonstrated the effectiveness of JY-1-106 in this animal model. No significant side effects were observed in mouse organs after multiple injections. CONCLUSIONS: Taken together, these observations demonstrate that JY-1-106 is an effective pan-Bcl-2 inhibitor with very promising clinical potential.

Understanding determinants of consumer mobile health usage intentions, assimilation, and channel preferences.

BACKGROUND: Consumer use of mobile devices as health service delivery aids (mHealth) is growing, especially as smartphones become ubiquitous. However, questions remain as to how consumer traits, health perceptions, situational characteristics, and demographics may affect consumer mHealth usage intentions, assimilation, and channel preferences. OBJECTIVE: We examine how consumers' personal innovativeness toward mobile services (PIMS), perceived health conditions, health care availability, health care utilization, demographics, and socioeconomic status affect their (1) mHealth usage intentions and extent of mHealth assimilation, and (2) preference for mHealth as a complement or substitute for in-person doctor visits. METHODS: Leveraging constructs from research in technology acceptance, technology assimilation, consumer behavior, and health informatics, we developed a cross-sectional online survey to study determinants of consumers' mHealth usage intentions, assimilation, and channel preferences. Data were collected from 1132 nationally representative US consumers and analyzed by using moderated multivariate regressions and ANOVA. RESULTS: The results indicate that (1) 430 of 1132 consumers in our sample (37.99%) have started using mHealth, (2) a larger quantity of consumers are favorable to using mHealth as a complement to in-person doctor visits (758/1132, 66.96%) than as a substitute (532/1132, 47.00%), and (3) consumers' PIMS and perceived health conditions have significant positive direct influences on mHealth usage intentions, assimilation, and channel preferences, and significant positive interactive influences on assimilation and channel preferences. The independent variables within the moderated regressions collectively explained 59.70% variance in mHealth usage intentions, 60.41% in mHealth assimilation, 34.29% in preference for complementary use of mHealth, and 45.30% in preference for substitutive use of mHealth. In a follow-up ANOVA examination, we found that those who were more favorable toward using mHealth as a substitute for in-person doctor visits than as a complement indicated stronger intentions to use mHealth (F1,702=20.14, P<.001) and stronger assimilation of mHealth (F1,702=41.866, P<.001). CONCLUSIONS: Multiple predictors are shown to have significant associations with mHealth usage intentions, assimilation, and channel preferences. We suggest that future initiatives to promote mHealth should shift targeting of consumers from coarse demographics to nuanced considerations of individual dispositions toward mobile service innovations, complementary or substitutive channel use preferences, perceived health conditions, health services availability and utilization, demographics, and socioeconomic characteristics.

Understanding how physician perceptions of job demand and process benefits evolve during CPOE implementation.

We examine how physicians' perceptions of two computerized provider order entry (CPOE) capabilities, standardisation of care protocols and documentation quality, are associated with their perceptions of turnaround time, medical error, and job demand at three phases of CPOE implementation: pre-go-live, initial use, and continued use. Through a longitudinal study at a large urban hospital, we find standardisation of care protocols is positively associated with turnaround time reduction in all phases but positively associated with job demand increase only in the initial use phase. Standardisation also has a positive association with medical error reduction in the initial use phase, but later this effect becomes fully mediated through turnaround time reduction in the continued use phase. Documentation quality has a positive association with medical error reduction in the initial use phase and this association strengthens in the continued use phase. Our findings provide insights to effectively manage physicians' response to CPOE implementation.

Prospective Randomized Trial of Antibiotic Prophylaxis Duration for Percutaneous Nephrolithotomy in Low-Risk Patients.

Introduction and Objective: Postoperative infection and sepsis account for the most common complications following percutaneous nephrolithotomy (PCNL), as high as 14% in low-risk patients. Although the American Urological Association (AUA) recommends perioperative antibiotics for 24 hours or less for PCNL, practice patterns vary regarding duration of antibiotic therapy. We aimed to compare the efficacy of 24-hour antibiotic coverage vs short-course protocol of antibiotic prophylaxis for PCNL. Materials and Methods: Low-risk patients with a sterile preoperative urine culture undergoing PCNL were prospectively randomized to antibiotics for up to 24 hours after procedure (24Hr) or continued until external urinary catheters were removed (CR) study groups. Patients were given a first generation cephalosporin, or ciprofloxacin in patients with penicillin allergy. Exclusion criteria included age <18 years, receiving antibiotics immediately before the procedure, history of urosepsis, presence of indwelling catheter >1 week, multistage procedure, immunosuppression, pregnancy, multiple antibiotic allergies, and patients who are breastfeeding. Results: Ninety-eight patients were randomized to either 24Hr (n = 49) or CR (n = 49). Mean duration of antibiotic administration was 20.6 and 34.0 hours in the 24Hr and CR groups (p = 0.04), respectively. Age, comorbidities, stone size, operative time, number of punctures, dilations, and proportion of "tubeless" procedures were similar between groups. There were no differences in febrile episodes, rates of systemic inflammatory response syndrome, bacteremia, or culture-proven postoperative urinary tract infection between the 24Hr and CR groups. Overall complication rates were similar between groups. In a subgroup analysis which excluded "tubeless" patients (24 and 29 patients in 24Hr and CR groups, respectively), no differences were seen in postoperative outcomes. Conclusions: In a randomized, prospective study, we found that a 24-hour protocol for antibiotic prophylaxis is not associated with increased risk of infection-related events compared to giving antibiotics until external catheters are removed in patients with low infectious risk undergoing PCNL. Clinicaltrials.gov: NCT02579161.

The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition.

BACKGROUND: It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination. METHODS: The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell lines were determined by western blotting. Annexin-V staining and cleaved PARP western blotting were used to assay for apoptosis. The cellular toxicities after various treatments were measured via the XTT assay. RESULTS: In our current analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL are overexpressed and also co-exist in many tumors and that the expression levels of both genes correlate with the clinical staging. The downregulation of Mcl-1 or Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates with that of Mcl-1 in human cancer tissue samples. We additionally found that the USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and promoted apoptosis in different tumor cells. CONCLUSION: Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors.

Application of biological systems and processes employing microbes and algae to Reduce, Recycle, Reuse (3Rs) for the sustainability of circular bioeconomy.

The circular bioeconomy has undoubtedly gained global momentum during the last few years. The bioeconomy envisions "3R", the goal of 3R (Reduce, Recycle, Reuse) is to implement in circular economy preventing excessive and unnecessary wastes. The circular bioeconomy emphasizes the best use of all sorts of available bioresources through the reduction of generated wastes during product formation, recycling of generated wastes, and reuse of valuable by-products and residues. Biotechnology could be useful in utilizing the resources to the optimum and therefore the role of biological agents and bioprocesses is of prime importance. In this review, we highlight the paramount importance of beneficial strains of microorganisms, macro, and microalgae in the bioeconomy. Microorganisms are universally recognized for the notable production of a vast array of secondary metabolites and other functionalities with possible use in various sectors. The application of potential strains in industries and modern agriculture practices could progressively improve the effective yield of food and feed, including fertilization of arid soils, bioconversion of by-products from industrial processes, and agriculture wastes. The valuable properties of specifically selected biological agents typically make them suitable candidates for their efficient contribution to circular bioeconomy without hampering the environment.

Utility of Frailty Assessment in Urologic Stone Surgery: A Review of the Literature.

Introduction and Objective: As life expectancy continues to rise, the prevalence of frailty is also increasing. The idea of frailty and its effect on the operative patient has been previously studied, but not regularly incorporated into routine practice. We present a review on frailty metrics in the literature, validated assessment methods, and simplified screening tools to better predict and optimize patient outcomes. Methods: An online PubMed search was conducted by three authors (T.A., T.G.R.B., M.M.) for overall frailty, frailty assessment, and preoperative risk assessment. Only English publications were included in the analysis. Full-text analysis was then conducted by all three authors to validate the data. Results: An abundance of literature was found on frailty. Even though some methods are validated as extremely effective for assessing frailty, they may be time-consuming and require a specialist. Various quick screening methods are also presented, many already validated, and should be utilized by urologists more regularly. Conclusions: Multiple studies demonstrate the relationship between frailty and surgical patients' outcome. Many quick, office-based, validated tools to screen for frailty are described, and should be incorporated into our practice in appropriate patients. Future research is now focused on the concept of "prehabilitation" to improve patient frailty status in the preoperative setting, and consequently operative outcomes.

Lactic acid bacteria isolated from ethnic preserved meat products of the Western Himalayas.

We used culture- and molecular-biology-based methods to investigate the diversity of lactic acid bacteria (LAB) in the ethnic chevon (goat) meat products chartayshya, jamma and arjia of the Western Himalayas. In six chartayshya, six jamma and four arjia samples, LAB were the predominant microbial component involved in the fermentation of these samples, and the total LAB population in arjia (7.8 ± 0.1 log cfu g(-1); mean ± SD) was significantly higher (P < 0.05) than in chartayshya (6.9 ± 0.1 log cfu g(-1)) and jamma (7.5 ± 0.1 log cfu g(-1)). We identified 53 LAB samples by 16S rRNA and phenylalanyl-tRNA synthase (pheS) genes sequencing. The LAB isolates were identified as Enterococcus durans, Enterococcus faecalis, Enterococcus faecium, Enterococcus hirae, Leuconostoc citreum, Leuconostoc mesenteroides, Pediococcus pentosaceus, and Weissella cibaria. These results revealed that there is a high level of diversity of LAB in the Himalayan ethnic preserved meat products.

Laparoscopic Radical Nephrectomy.

In addition to its established advantages, laparoscopic radical nephrectomy (RN) poses a unique set of challenges over traditional open surgery. In this study, we discuss preoperative considerations and detailed steps for laparoscopic RN. We review the transabdominal approach in detail, including patient positioning, equipment, and port placement in addition to the surgical steps. Intraoperative decisions such as adrenal management, renal preservation, and tumor identification are reviewed. Common complications of laparoscopic renal surgery are also summarized.

Exploring endophytes for in vitro synthesis of bioactive compounds similar to metabolites produced in vivo by host plants.

Endophytes represent microorganisms residing within plant tissues without typically causing any adverse effect to the plants for considerable part of their life cycle and are primarily known for their beneficial role to their host-plant. These microorganisms can in vitro synthesize secondary metabolites similar to metabolites produced in vivo by their host plants. If microorganisms are isolated from certain plants, there is undoubtedly a strong possibility of obtaining beneficial endophytes strains producing host-specific secondary metabolites for their potential applications in sustainable agriculture, pharmaceuticals and other industrial sectors. Few products derived from endophytes are being used for cultivating resilient crops and developing non-toxic feeds for livestock. Our better understanding of the complex relationship between endophytes and their host will immensely improve the possibility to explore their unlimited functionalities. Successful production of host-secondary metabolites by endophytes at commercial scale might progressively eliminate our direct dependence on high-valued vulnerable plants, thus paving a viable way for utilizing plant resources in a sustainable way.

Novel Irrigation Protocol for Renal Pelvis Sterilization During Percutaneous Nephrolithotomy: A Pilot Study.

While percutaneous nephrolithotomy (PCNL) remains the treatment modality of choice for kidney stones larger than 2 cm, infectious complications are most common, ranging from 5% to 32%. We present here a novel technique for potentially improving collecting system sterility during PCNL and initial postoperative outcomes. Retrospective chart analysis data of our irrigation protocol were collected from our first 56 patients between February and July 2019. Traditional prone PCNL was performed in a standard manner using fluoroscopic guidance. Using a ureteral catheter that was placed cystoscopically, a renal pelvis urine culture was taken and subsequently 10 mL of betadine solution was instilled into the collecting system. Gentamicin in normal saline (80 mg/3 L) was utilized as the irrigant fluid for the first 6 L of irrigation. From this cohort, 57% patients were women and mean age was 60 ± 14 years. About 23% of patients were diabetic and 55% were hypertensive. Seventy percent of patients had stone burden >2 cm and no patients had stone burden <1 cm. Fifteen patients had positive urine cultures treated preoperatively, while four patients had contaminated cultures. All patients were treated with our antibiotic irrigation and betadine protocol regardless of preoperative cultures or antibiotics. Mean baseline creatinine level was 0.95 ± 0.41, with a mean change of 0.18 at postoperative day 1. Of the 15 (26%) of 56 patients with a systemic inflammatory response syndrome response (two of following four criteria: white blood cells <4 or >12; heart rate >90; hypothermia <96.8°F or hyperthermia >100.4°F; and respiratory rate >20), only six patients (11%) were febrile and two patients had positive blood cultures (3%). There were no adverse reactions to the betadine or antibiotic irrigation. We present here our initial experience of a new technique for renal pelvis sterilization and its safety and feasibility using intrarenal instillation of betadine and antibiotic irrigation. No Clinical Trial Registration number applicable.

Conservative Management of Liver Perforation During Percutaneous Nephrolithotomy: Case Couplet Presentation.

Percutaneous nephrolithotomy (PCNL) remains the recommended intervention for large kidney stones, major complications, although rare, are between 1% and 7%. Literature regarding liver injury during PCNL is sparse, and many incidences occur unnoticed. In general, most liver injuries can be treated conservatively when compared with other organ injury sustained during PCNL. Despite this, there is still significant potential for intraperitoneal bleeding as well as possible hemodynamic instability that may result secondary to the inadvertent access. Our team describes two cases of liver injury during PCNL with focus on presentation and injury management. Both cases were treated conservatively through close clinical monitoring and delayed removal of nephrostomy tube. Both liver injuries were diagnosed primarily through postprocedure axial CT imaging. In general, risk factors include supracostal access, particularly at or above the 11th rib, as well as hepatomegaly. Despite that liver injury is a rare complication of right-sided PCNL, outcomes can result in significant blood loss not diagnosed. We present in this study two instances of effective conservative management of liver injury after PCNL.

Management of Colon Perforation During Percutaneous Nephrolithotomy in Patients with Complex Anatomy: A Case Series.

Percutaneous nephrolithotomy (PCNL), first described in 1976, is the gold standard for the management of large kidney stones, with stone-free rates as high as 95% in contemporary literature. Colonic injuries during PCNL are a rare complication with an estimated incidence of 0.3%-0.5%. However, given the high morbidity incurred and the necessity of prompt operative intervention, it is imperative that practitioners have a low suspicion threshold for such injuries, particularly in those patients with altered or complex anatomy. This case series addresses peri- and postoperative outcomes of colon perforation during PCNL in patients with complex anatomy and reviews the technical challenges of surgery with potential methods to avoid injury in the future. Herein we review three instances of colonic injuries and their subsequent management to highlight both the presentation and the optimal management of these rare occurrences.

Management of Splenic Injury During Percutaneous Nephrolithotomy: Report of Two Cases.

Percutaneous nephrolithotomy (PCNL) has become the standard of care for the removal of kidney stones >2 cm. Major complications, although rare, are between 1% and 7%. Splenic injury during PCNL is rare and can often be managed conservatively, but has the potential to be devastating, necessitating the importance of early diagnosis. Our team describes two cases of splenic injury during PCNL with emphasis on diagnosis and management. Although both cases were managed conservatively through close monitoring and prolonged nephrostomy tube presence, one case had a concurrent pneumothorax. Both cases were diagnosed primarily through postprocedure CT imaging. Risk factors primarily include supracostal access and splenomegaly. Splenic injury is a rare complication that can often be managed conservatively; however, prompt recognition of injury is important. We present in this study two cases of conservative splenic injury management sustained during PCNL.