The Management of Large Bladder Calculi by Utilizing Dual-Action Percutaneous Lithotripsy via Suprapubic Tube Sheath: A Novel Technique.

Bladder calculi commonly develop in patients with poor bladder emptying or those with retained foreign bodies within the bladder, leading to irritative voiding symptoms, hematuria, and an increased likelihood of refractory urinary tract infections. While many techniques exist for the treatment of bladder calculi, including endoscopic and open-surgical approaches, our novel technique may help manage exceptionally large or difficult-to-treat bladder calculi effectively. We present three patients with symptomatic bladder calculi ranging from 1.3 cm to 6.8 cm in size who were successfully treated by using our novel technique. Percutaneous access to the bladder was obtained by using a suprapubic catheter trocar and sheath to enable the utilization of a dual-action lithotriptor. Sheath insertion and lithotripsy were performed under direct visualization with a rigid cystoscope via the native urethra. This technique is easily learned and can be safely employed in patients in whom other methods may pose risks of higher morbidity.

Is Urethral Catheterization Necessary in Retzius-sparing Robot-assisted Radical Prostatectomy?

OBJECTIVE: To analyze whether urethral catheter (UC)-free anastomosis during Retzius-sparing radical prostatectomy (RP) results in worsening immediate perioperative and postoperative complications. METHODS: We retrospectively reviewed records of patients undergoing robotic-assisted RP with or without indwelling UC placement by a single surgeon between January 2020 and March 2022. Clinical and pathological characteristics were evaluated. An independent t-test was used to compare continuous variables, and Pearson's chi-square test or Fisher exact test was used to compare categorical variables. RESULTS: One hundred fifteen patients underwent robotic prostatectomy from January 2020 to June 2022. Sixty-two patients had both a UC for 12 hours postoperatively and a suprapubic catheter for 6days, while in 53 patients a UC was omitted. There was no significant difference noted between the groups regarding age, body mass index, American Society of Anesthesiology score, prostate-specific antigen, stage, node status, or positive margins. There were no significant differences in the rates of anastomotic leak, ileus, or urethral stricture. Patients had a significantly higher pad-free rate in the suprapubic catheter-only group (P = .04) at 3months. There was no difference in average number of pads used or the number using more than 1 pad/day. CONCLUSION: Omission of urethral catheterization during Retzius-sparing RP is safe and doesn't result in an increased risk in perioperative or postoperative complications, but rather appears to be associated with a significantly improved 3-month pad-free rate.

Diabetic kidney disease induces transcriptome alterations associated with angiogenesis activity in human mesenchymal stromal cells.

BACKGROUND: Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach. METHODS: To explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment. Next-generation RNA sequencing (RNA-seq) was performed on MSC (DKD n = 29; Controls n = 9) to identify differentially expressed (DE; adjusted p < 0.05, |log2fold change|> 1) messenger RNA (mRNA) and microRNA (miRNA) involved in angiogenesis (GeneCards). Paracrine-mediated angiogenic repair capacity of MSC conditioned medium (MSCcm) was assessed in vitro using human umbilical vein endothelial cells incubated in high glucose and indoxyl sulfate for a hyperglycemic, uremic state. RESULTS: RNA-seq analyses revealed 133 DE mRNAs (77 upregulated and 56 down-regulated) and 208 DE miRNAs (119 up- and 89 down-regulated) in DKD-MSC versus Control-MSC. Interestingly, miRNA let-7a-5p, which regulates angiogenesis and participates in DKD pathogenesis, interacted with 5 angiogenesis-associated mRNAs (transgelin/TAGLN, thrombospondin 1/THBS1, lysyl oxidase-like 4/LOXL4, collagen 4A1/COL4A1 and collagen 8A1/COL8A1). DKD-MSCcm incubation with injured endothelial cells improved tube formation capacity, enhanced migration, reduced adhesion molecules E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 mRNA expression in endothelial cells. Moreover, angiogenic repair effects did not differ between treatment groups (DKD-MSCcm vs. Control-MSCcm). CONCLUSIONS: MSC from individuals with DKD show angiogenic transcriptome alterations compared to age-matched controls. However, angiogenic repair potential may be preserved, supporting autologous MSC interventions to treat conditions requiring enhanced angiogenic activities such as DKD, diabetic foot ulcers, and critical limb ischemia.

Visual Acuity as a Measurement of Visual Function.

Visual acuity (VA) is a traditional measure of central visual function, particularly the ability of the eye to perceive details. In a clinical setting, standardized charts are commonly used to quickly assess VA. Namely, the Early Treatment of Diabetic Retinopathy Study (ETDRS) VA test chart is the gold standard for VA testing in the clinical setting. This chapter outlines the standard procedures associated with measuring VA.

Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as acute renal failure.

Lymphoma of the urinary bladder is quite rare, accounting for a small percentage of all bladder neoplasms. Here we discuss the case of a 68-year-old male patient who initially presented with acute renal failure and severe bilateral hydronephrosis on ultrasound. Cross-sectional imaging further revealed a diffusely thickened bladder wall with extensive retroperitoneal and mesenteric lymphadenopathy. Bladder biopsies ultimately led to a diagnosis of stage IV chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This is a rare instance of upper tract dilatation being the first sign of a widely disseminated hematologic malignancy.

Agonist that activates the µ-opioid receptor in acidified microenvironments inhibits colitis pain without side effects.

OBJECTIVE: The effectiveness of µ-opioid receptor (MOPr) agonists for treatment of visceral pain is compromised by constipation, respiratory depression, sedation and addiction. We investigated whether a fentanyl analogue, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), which preferentially activates MOPr in acidified diseased tissues, would inhibit pain in a preclinical model of inflammatory bowel disease (IBD) without side effects in healthy tissues. DESIGN: Antinociceptive actions of NFEPP and fentanyl were compared in control mice and mice with dextran sodium sulfate colitis by measuring visceromotor responses to colorectal distension. Patch clamp and extracellular recordings were used to assess nociceptor activation. Defecation, respiration and locomotion were assessed. Colonic migrating motor complexes were assessed by spatiotemporal mapping of isolated tissue. NFEPP-induced MOPr signalling and trafficking were studied in human embryonic kidney 293 cells. RESULTS: NFEPP inhibited visceromotor responses to colorectal distension in mice with colitis but not in control mice, consistent with acidification of the inflamed colon. Fentanyl inhibited responses in both groups. NFEPP inhibited the excitability of dorsal root ganglion neurons and suppressed mechanical sensitivity of colonic afferent fibres in acidified but not physiological conditions. Whereas fentanyl decreased defecation and caused respiratory depression and hyperactivity in mice with colitis, NFEPP was devoid of these effects. NFEPP did not affect colonic migrating motor complexes at physiological pH. NFEPP preferentially activated MOPr in acidified extracellular conditions to inhibit cAMP formation, recruit ß-arrestins and evoke MOPr endocytosis. CONCLUSION: In a preclinical IBD model, NFEPP preferentially activates MOPr in acidified microenvironments of inflamed tissues to induce antinociception without causing respiratory depression, constipation and hyperactivity.

Extensive loss of Wnt genes in Tardigrada.

BACKGROUND: Wnt genes code for ligands that activate signaling pathways during development in Metazoa. Through the canonical Wnt (cWnt) signaling pathway, these genes regulate important processes in bilaterian development, such as establishing the anteroposterior axis and posterior growth. In Arthropoda, Wnt ligands also regulate segment polarity, and outgrowth and patterning of developing appendages. Arthropods are part of a lineage called Panarthropoda that includes Onychophora and Tardigrada. Previous studies revealed potential roles of Wnt genes in regulating posterior growth, segment polarity, and growth and patterning of legs in Onychophora. Unlike most other panarthropods, tardigrades lack posterior growth, but retain segmentation and appendages. Here, we investigated Wnt genes in tardigrades to gain insight into potential roles that these genes play during development of the highly compact and miniaturized tardigrade body plan. RESULTS: We analyzed published genomes for two representatives of Tardigrada, Hypsibius exemplaris and Ramazzottius varieornatus. We identified single orthologs of Wnt4, Wnt5, Wnt9, Wnt11, and WntA, as well as two Wnt16 paralogs in both tardigrade genomes. We only found a Wnt2 ortholog in H. exemplaris. We could not identify orthologs of Wnt1, Wnt6, Wnt7, Wnt8, or Wnt10. We identified most other components of cWnt signaling in both tardigrade genomes. However, we were unable to identify an ortholog of arrow/Lrp5/6, a gene that codes for a Frizzled co-receptor of Wnt ligands. Additionally, we found that some other animals that have lost several Wnt genes and are secondarily miniaturized, like tardigrades, are also missing an ortholog of arrow/Lrp5/6. We analyzed the embryonic expression patterns of Wnt genes in H. exemplaris during developmental stages that span the establishment of the AP axis through segmentation and leg development. We detected expression of all Wnt genes in H. exemplaris besides one of the Wnt16 paralogs. During embryo elongation, expression of several Wnt genes was restricted to the posterior pole or a region between the anterior and posterior poles. Wnt genes were expressed in distinct patterns during segmentation and development of legs in H. exemplaris, rather than in broadly overlapping patterns. CONCLUSIONS: Our results indicate that Wnt signaling has been highly modified in Tardigrada. While most components of cWnt signaling are conserved in tardigrades, we conclude that tardigrades have lost Wnt1, Wnt6, Wnt7, Wnt8, and Wnt10, along with arrow/Lrp5/6. Our expression data may indicate a conserved role of Wnt genes in specifying posterior identities during establishment of the AP axis. However, the loss of several Wnt genes and the distinct expression patterns of Wnt genes during segmentation and leg development may indicate that combinatorial interactions among Wnt genes are less important during tardigrade development compared to many other animals. Based on our results, and comparisons to previous studies, we speculate that the loss of several Wnt genes in Tardigrada may be related to a reduced number of cells and simplified development that accompanied miniaturization and anatomical simplification in this lineage.

Analysis of SARS-CoV-2 RNA on surfaces in New York City.

BACKGROUND: This study sought to determine the presence of SARS-CoV-2 virus on surfaces that trainees and faculty of an academic eye clinic came into contact with during daily life at the time of the COVID-19 pandemic in New York City. METHODS: This cross-sectional analysis involved collection of at least two samples by teams on four different days (November 9, 2020 - December 18, 2020) using sterile swabs (Puritan HydraFlock, Garden Grove, CA). Collection sites were grouped into four zones depending on proximity and amount of time personnel spent there. Samples were transported to the laboratory in transport medium and RNA was extracted using the QIAamp DSP Viral RNA Mini Kit (Qiagen, Germantown, MD). Presence of viral RNA was investigated using the Luna Universal Probe One-step RT-qPCR kit (New England Biolabs, Ipwsich, MA). RESULTS: 834 samples were submitted. Two were positive for SARS-CoV-2 RNA. The first was a sample from a patient bathroom sink handle in the main emergency department. The second was a nasal swab sample from a staff member who had been assigned to collect samples. Prior to this positive result, this asymptomatic staff member had tested positive for COVID-19, had quarantined for two weeks, and had received a negative test. CONCLUSION: Though COVID-19 is currently widespread in the United States, this study shows that health care personnel working in New York City at the Columbia University Irving Medical Center have a low chance of encountering viral RNA on surfaces they are in close contact with during daily life.

Nephroureterectomy vs. segmental ureterectomy of clinically localized, high-grade, urothelial carcinoma of the ureter: Practice patterns and outcomes.

BACKGROUND: Nephroureterectomy (NU) remains the gold-standard for upper-tract urothelial carcinoma (UTUC). However, nephron-sparing management (NSM), specifically segmental ureterectomy (SU) for urothelial tumors distal to the renal pelvis may offer decreased risk of renal insufficiency and equivalent cancer control. OBJECTIVES: To identify patient-specific and facility-related factors that are associated with the selection of SU vs. NU for patients with clinically localized, high-grade, ureteral UTUC. DESIGN, SETTING, PARTICIPANTS: We searched the National Cancer Database between 2004 and 2015 for patients with high-grade, clinically localized, primary ureteral UTUC managed by either NU or SU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariate and multivariate analysis was performed to assess patient, disease-specific, facility and treatment-related factors associated with SU vs. NU. Since surgical approach was only indexed after 2010, separate multivariable logistic regressions were performed including and excluding surgical approach in order to capture patients treated between 2004 and 2009. Survival analysis utilized Kaplan-Meier methods and Cox proportional hazards regression. RESULTS AND LIMITATIONS: Multivariate analysis including surgical approach demonstrated that among other factors, higher clinical stage (P = 0.034), larger tumor size (P < 0.001), the addition of neoadjuvant chemotherapy (P = 0.002), and the utilization of minimally invasive surgery (P < 0.05) decreased the likelihood of patients receiving SU. In this same cohort, institutions with larger facility volumes (P = 0.038) and performing intraoperative lymph node dissection (P < 0.001) were associated with a higher probability of SU. Excluding surgical approach, once again more advanced clinical stage (P = 0.005), larger tumor size (P < 0.001), and neoadjuvant chemotherapy (P = 0.003) decreased the probability of patients receiving SU, while increasing age (P = 0.049) and intraoperative lymph node dissection (P < 0.001) were more closely associated with SU compared to NU. No differences were noted in pathological T stage (P > 0.05), 30-day readmission (P = 0.7), 30-day mortality (P = 0.09), and 90-day mortality (P = 0.157) on multivariate analysis between SU and NU. Additionally, no significant differences were seen in median overall survival between patients receiving SU or NU (53 vs. 50 months; P = 0.143). CONCLUSIONS: Comparable outcomes suggest segmental ureterectomy for high-grade ureteral UTUC is appropriate in well-selected patients. Practice patterns appear consistent with guideline recommendations (decreased tumor size and lower clinical stage favor SU), but treatment disparities may exist based on a multitude of patient, pathologic- and facility-related factors. Improved dissemination of knowledge regarding practice patterns and outcomes of SU for UTUC of the ureter has the potential to improve delivery of NSM in appropriate patients. PATIENT SUMMARY: In this study, we examined factors associated with different surgical procedures for cancer of the ureter. We found that smaller tumor sizes, a less advanced clinical stage, intraoperative lymph dissection higher facility volumes tended to favor kidney-sparing treatment, while survival outcomes appear comparable to renal extirpation.

Paraganglioma of the Spermatic Cord With Spinal Metastasis: A Case Report.

A 40-year-old male with presented to the clinic with the chief complaint of right inguinal pain radiating to his right testicle and right thigh with no history of trauma, fever, chills, dysuria, hematuria, or unprotected sexual activity. Physical exam revealed right testicular tenderness with no palpable abnormality of the bilateral testes or spermatic cords. Scrotal ultrasound was performed and was unremarkable for testicular or other intrascrotal pathology. Concurrently, chronic low back pain had prompted a lumbar CT to be performed, which was indeterminate, but subsequent lumbar MRI performed three months later revealed abnormal signals in the vertebral bodies of T12, L3, and L5, concerning for occult metastatic disease or multiple myeloma. PET-CT was performed revealing hypermetabolic lesions throughout the axial skeleton and, most notably, hypermetabolic lesions in the left inguinal and left upper scrotum. At this time, about 4 months after the original visit, physical exam revealed a palpable mobile mass in the left upper scrotum that was distinct from the left testicle, and another mass palpable near the left inguinal ring.

Characterization and clinical course of 1000 patients with COVID-19 in New York: retrospective case series.

Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. Results: Among the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.

Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series.

OBJECTIVE: To characterize patients with coronavirus disease 2019 (covid-19) in a large New York City medical center and describe their clinical course across the emergency department, hospital wards, and intensive care units. DESIGN: Retrospective manual medical record review. SETTING: NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center in New York City. PARTICIPANTS: The first 1000 consecutive patients with a positive result on the reverse transcriptase polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to the emergency department or were admitted to hospital between 1 March and 5 April 2020. Patient data were manually abstracted from electronic medical records. MAIN OUTCOME MEASURES: Characterization of patients, including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. RESULTS: Of the first 1000 patients, 150 presented to the emergency department, 614 were admitted to hospital (not intensive care units), and 236 were admitted or transferred to intensive care units. The most common presenting symptoms were cough (732/1000), fever (728/1000), and dyspnea (631/1000). Patients in hospital, particularly those treated in intensive care units, often had baseline comorbidities including hypertension, diabetes, and obesity. Patients admitted to intensive care units were older, predominantly male (158/236, 66.9%), and had long lengths of stay (median 23 days, interquartile range 12-32 days); 78.0% (184/236) developed acute kidney injury and 35.2% (83/236) needed dialysis. Only 4.4% (6/136) of patients who required mechanical ventilation were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at three to four days, and at nine days. As of 30 April, 90 patients remained in hospital and 211 had died in hospital. CONCLUSIONS: Patients admitted to hospital with covid-19 at this medical center faced major morbidity and mortality, with high rates of acute kidney injury and inpatient dialysis, prolonged intubations, and a bimodal distribution of time to intubation from symptom onset.

Robotic Management of Urolithiasis in the Pediatric Population.

A variety of surgical techniques exist for the management of urolithiasis. Minimally invasive techniques have replaced open surgery in the last few decades. For complex stone management, robotic-assisted laparoscopic surgery (RALS) has emerged as a safe and feasible alternative in adults. The literature for RALS for urolithiasis (RALS-UL) in the pediatric population is scarce. Herein, we present a review of the literature in both adult and pediatric patients as well as our experience using RALS-UL at our institutions. Special attention is given to the synchronous management of urolithiasis when surgery is performed for other conditions such as ureteropelvic junction obstruction (UPJO), and a supplemental video is provided.

A four-gene operon in Bacillus cereus produces two rare spore-decorating sugars.

Bacterial glycan structures on cell surfaces are critical for cell-cell recognition and adhesion and in host-pathogen interactions. Accordingly, unraveling the sugar composition of bacterial cell surfaces can shed light on bacterial growth and pathogenesis. Here, we found that two rare sugars with a 3-C-methyl-6-deoxyhexose structure were linked to spore glycans in Bacillus cereus ATCC 14579 and ATCC 10876. Moreover, we identified a four-gene operon in B. cereus ATCC 14579 that encodes proteins with the following sequential enzyme activities as determined by mass spectrometry and one- and two-dimensional NMR methods: CTP:glucose-1-phosphate cytidylyltransferase, CDP-Glc 4,6-dehydratase, NADH-dependent SAM:C-methyltransferase, and NADPH-dependent CDP-3-C-methyl-6-deoxyhexose 4-reductase. The last enzyme predominantly yielded CDP-3-C-methyl-6-deoxygulose (CDP-cereose) and likely generated a 4-epimer CDP-3-C-methyl-6-deoxyallose (CDP-cillose). Some members of the B. cereus sensu lato group produce CDP-3-C-methyl-6-deoxy sugars for the formation of cereose-containing glycans on spores, whereas others such as Bacillus anthracis do not. Gene knockouts of the Bacillus C-methyltransferase and the 4-reductase confirmed their involvement in the formation of cereose-containing glycan on B. cereus spores. We also found that cereose represented 0.2-1% spore dry weight. Moreover, mutants lacking cereose germinated faster than the wild type, yet the mutants exhibited no changes in sporulation or spore resistance to heat. The findings reported here may provide new insights into the roles of the uncommon 3-C-methyl-6-deoxy sugars in cell-surface recognition and host-pathogen interactions of the genus Bacillus.