Periprosthetic Hip and Knee Infection: Is an Ipsilateral Uninfected Total Joint Arthroplasty at Risk?

BACKGROUND: Periprosthetic joint infections (PJIs) of total hip arthroplasty (THA) or total knee arthroplasty (TKA) may occur in the setting of an uninfected ipsilateral prosthetic joint. However, the risk to that uninfected ipsilateral joint is unknown. We analyzed the survivorship free from PJI in at risk THAs and TKAs following treatment of an ipsilateral knee or hip PJI, respectively. METHODS: Using our institutional total joint registry, we identified 205 patients who underwent treatment for PJI (123 THAs and 83 TKAs) with an at-risk ipsilateral in situ knee or hip, respectively, between 2000 and 2019. In total, 54% of index PJIs were chronic and 46% were acute. The mean age was 70 years, 47% were female, and the mean body mass index was 32. Kaplan-Meier survivorship analyses were performed. Mean follow-up was 6 years. RESULTS: The 5-year survivorship free of PJI in an at-risk THA after an ipsilateral TKA was treated for PJI was 97%. The 5-year survivorship free of PJI in an at-risk TKA when the ipsilateral THA was treated for PJI was 99%. Three PJIs occurred (2 THAs and 1 TKA), all over 1 year from the index ipsilateral PJI treatment. One hip PJI was an acute hematogenous infection that resulted from pneumonia. The other 2 new PJIs were caused by the same organism as the index PJI and were due to a failure of source control at the index joint. CONCLUSIONS: When diagnosed with PJI in a single joint, the risk of developing PJI in an ipsilateral prosthetic joint within 5 years was low (1 to 3% risk). In the rare event of an ipsilateral infection, all occurred greater than one year from the index PJI and 2 of 3 were with the same organism when source infection control failed. LEVEL OF EVIDENCE: Prognostic Level III.

Knee Arthroscopy Following Total Knee Arthroplasty is Not Associated With an Elevated Risk of Infection.

BACKGROUND: Recent literature has suggested that knee arthroscopy (KA) following ipsilateral primary total knee arthroplasty (TKA) may be associated with an increased risk of periprosthetic joint infection (PJI). However, prior studies on this subject have relied on insurance databases or have lacked control groups for comparison. This study aimed to evaluate the risk of PJI in patients undergoing ipsilateral KA after primary TKA at a single institution. METHODS: Our total joint registry was queried to identify 167 patients (178 knees) who underwent ipsilateral KA for any indication other than infection following primary TKA (KA + TKA group). The average time from TKA to KA was 2.1 ± 2.3 years. The average follow-up from primary TKA and from KA was 8.4 ± 5.4 years and 6.3 ± 5.4 years, respectively. The mean patient age was 63 ± 11 years, the mean body mass index was 31 ± 5, and 64% were women. The most common indications for KA were patellar clunk or patellofemoral synovial hyperplasia (66%) and arthrofibrosis (16%). Patients in the KA + TKA group were matched to 523 patients who underwent TKA without subsequent KA (TKA group) based on age, sex, date of surgery, and body mass index. The primary outcome measure was survivorship free from PJI. RESULTS: There was no statistical difference in the overall rate of PJI between the KA + TKA group (n = 2, 1.1%) compared to the TKA group (n = 3, 0.6%) (hazard ratio 2.0, 95% confidence interval 0.3 to 12.0, P = .4). At 5 and 10 years after TKA, there was no difference in survivorship free of PJI between the 2 groups (P = .8 and P = .3, respectively). CONCLUSIONS: A PJI is a rare complication of KA after TKA. The rate of PJI in patients undergoing KA following TKA is not significantly increased. LEVEL OF EVIDENCE: III.

Severe aortic stenosis: secular trends of incidence and outcomes.

BACKGROUND AND AIMS: Severe aortic stenosis (AS) is the guideline-based indication for aortic valve replacement (AVR), which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory and lack quantitative Doppler echocardiographic ascertainment. METHODS: All adults residents in Olmsted County (MN, USA) diagnosed over 20 years (1997-2016) with incident severe AS (first diagnosis) based on quantitatively defined measures (aortic valve area ≤ 1 cm2, aortic valve area index ≤ 0.6 cm2/m2, mean gradient ≥ 40 mmHg, peak velocity ≥ 4 m/s, Doppler velocity index ≤ 0.25) were counted to define trends in incidence, presentation, treatment, and outcome. RESULTS: Incident severe AS was diagnosed in 1069 community residents. The incidence rate was 52.5 [49.4-55.8] per 100 000 patient-year, slightly higher in males vs. females and was almost unchanged after age and sex adjustment for the US population 53.8 [50.6-57.0] per 100 000 residents/year. Over 20 years, severe AS incidence remained stable (P = .2) but absolute burden of incident cases markedly increased (P = .0004) due to population growth. Incidence trend differed by sex, stable in men (incidence rate ratio 0.99, P = .7) but declining in women (incidence rate ratio 0.93, P = .02). Over the study, AS clinical characteristics remained remarkably stable and AVR performance grew and was more prompt (from 1.3 [0.1-3.3] years in 1997-2000 to 0.5 [0.2-2.1] years in 2013-16, P = .001) but undertreatment remained prominent (>40%). Early AVR was associated with survival benefit (adjusted hazard ratio 0.55 [0.42-0.71], P < .0001). Despite these improvements, overall mortality (3-month 8% and 3-year 36%), was swift, considerable and unabated (all P ≥ .4) throughout the study. CONCLUSIONS: Over 20 years, the population incidence of severe AS remained stable with increased absolute case burden related to population growth. Despite stable severe AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease lethality did not yet decline. These population-based findings have important implications for improving AS management pathways.

Impact of Neoadjuvant Chemotherapy on Pathologic Downstaging in Patients With Variant Histology Undergoing Radical Cystectomy.

INTRODUCTION: Variant histology (VH) bladder cancer is often associated with poor outcomes and the role of neoadjuvant chemotherapy (NAC) remains incompletely defined. Our objective was to determine comparative pathologic downstaging at radical cystectomy (RC) following NAC for patients with and without VH. PATIENTS AND METHODS: Patients who underwent RC at 2 tertiary referral centers (1996-2018) were included. Patients with VH (sarcomatoid, nested, micropapillary, plasmacytoid) were matched 1:2 to patients with pure urothelial carcinoma by age, sex, clinical T (cT)stage, clinical N (cN)stage, cystectomy year and receipt of NAC. The primary outcome was pathologic downstaging (pT-stage < cT-stage). The differential impact of NAC on pathologic downstaging between VH and non-VH was assessed using multivariable logistic regression with interaction analysis. RESULTS: 225 VH and 437 non-VH patients were included. One hundred twenty-eight of six hundred sixty-two (19.3%) patients experienced downstaging, including 54/121 (44.6%) patients who received NAC and 74/542 (13.2%) patients who did not (P < .01). Rates of downstaging after NAC for subgroups were: 45/78 (57.7%) urothelial, 3/8 (37.5%) sarcomatoid, 2/12 (16.7%) nested, 3/14 (21.4%) micropapillary, and 1/8 (12.5%) plasmacytoid. Collectively, 9/42 (21.4%) of VH patients who received NAC were downstaged. On multivariable analyses, NAC was associated with increased likelihood of downstaging in the overall cohort (OR 5.25, 95% CI, 3.29-8.36, P < .0001) and this effect was not modified by VH versus non-VH histology (P = .13 for interaction). VH patients had worse survival outcomes compared to non-VH (P < 0.01 for all). CONCLUSION: When comparing patients with VH to matched pure urothelial carcinoma controls, VH did not have an adverse effect on downstaging following NAC. VH patients should not be excluded from NAC if otherwise eligible.

Cutaneous Ureterostomy Following Radical Cystectomy for Bladder Cancer: A Contemporary Series.

OBJECTIVE: To report peri-operative outcomes of a contemporary series of bladder cancer patients undergoing radical cystectomy (RC) with cutaneous ureterostomy (CU) urinary diversion at a tertiary referral center. METHODS: We retrospectively identified patients who underwent RC with CU at Mayo Clinic between 2016 and 2021. Clinicopathologic and perioperative characteristics were analyzed using standard descriptive statistics. RESULTS: A total of 31 patients underwent RC with CU at our institution. Median age was 72years and 21 were male. This was highly comorbid cohort (83% had an American Society of Anesthesiologists [ASA] Physical Status Classification System ≥3; median Charlson Comorbidity index= 8). Median time to flatus, tolerating regular diet, and length of stay were 3 (interquartile range [IQR] 3-3), 3 (IQR 3-4), and 4days (IQR 4-7), respectively. A total of 14 patients experienced a high-grade complication (Clavien-Dindo ≥3) within 30days of surgery, and 8 were readmitted. The most common 30-day complication was sepsis, which affected 13% (4/31) of patients. At 90days postsurgery, the readmission rate was 32% (10/31), most commonly for sepsis. Three patients required reoperation within 90days, including one patient who required CU revision due to stomal ischemia. One patient died within this time frame from causes unrelated to bladder cancer. CONCLUSION: In a comorbid, relatively elderly bladder cancer cohort undergoing RC, the use of CU was associated with expeditious surgery and postoperative recovery. CU represents an option for urinary diversion in high-risk patients undergoing RC. Higher rate of postoperative ureteral obstruction can be pre-emptively addressed with chronic stent placement.

Laparoscopic anatomical segmentectomy: A paradigm shift towards minimally invasive liver surgery in Nepal: A cohort study.

Laparoscopic liver resection is taking stride in slowly replacing open surgeries for various hepatic pathologies in many developed countries. However, due to high cost and lack of expertise, there are only a handful of centres in the low-medium income countries who perform advanced laparoscopic liver resections regularly. In this study, a prospective analysis was carried out to assess and report the outcomes of laparoscopic anatomical segmentectomy (LAS) from a single centre in Nepal. Methods: The clinical data of all patients who underwent LAS between 1 October 2021 to 30 September 2022 were prospectively recorded. Demographics, pathological diagnoses, types of resections performed, perioperative parameters, postoperative length of stay, postoperative complications data and IWATE score were collected and analyzed. All operations were performed using the extrahepatic Glissonean technique with the use of indocyanine green dye as an adjunct during the intraoperative period. Results: In the study period, a total of 16 LAS were performed in our centre for various indications. The mean age of the patients in the series was 41.6 years, and seven of 16 patients were male. The majority of the cases were segment 2/3 resection indicated for various pathologies and segment 4b/5 indicated for carcinoma gallbladder. The median hospital stay was 6 days and only two cases developed major complication. There were no mortalities in our series. Conclusions: Taking into account the results produced from a single centre in a low-medium income country, laparoscopic anatomical segmentectomy is technically feasible with an acceptable safety profile.

Blunt Abdominal Trauma among Patients Admitted to the Department of Surgery at a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Blunt abdominal trauma bears significant morbidity and mortality worldwide and needs careful evaluation and management for a better outcome, where the resources are limited and the impact of the financial burden is very important. Previously, many cases used to be managed with operative procedures, and now the trend has been shifting to non-operative management. This study aimed to determine the prevalence of blunt abdominal trauma among patients admitted to the Department of Surgery of a tertiary care centre. Methods: This was descriptive cross-sectional study done between 1 February 2022 to 31 January 2023 after taking ethical approval from the Institutional Review Committee (Reference number: 2312202103). The decision of non-operative versus operative treatment was decided with dynamic clinical evaluation and severity of intraabdominal injuries. Demographic data, the mechanism of injury, and both conservative and operative management were studied. All the patients who were more than 18 years of age, and admitted to the Department of Surgery were included in the study. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Among a total of 1450 patients, the prevalence of blunt abdominal trauma was 140 (9.65%) (8.13-11.17, 95% Confidence Interval). A total of 61 (43.57%) were young within the age group of 18-30 with a male-female ratio of 4:1. Road traffic accidents 79 (56.43%) were the most common mechanism followed by falls from heights 51 (36.43%). Conclusions: The prevalence of blunt abdominal trauma among patients admitted to the Department of Surgery was found to be higher than in other studies done in similar settings. Keywords: blunt injuries; conservative management; operative surgical procedure.

Feasibility of Telementoring as an Intraoperative Time-out Tool during Laparoscopic Cholecystectomy for Prevention of Biliovascular Injuries.

Laparoscopic cholecystectomy is commonly performed procedure for gallbladder diseases. Biliovascular injuries are well known complications and various standard and safe strategies have been developed for safe cholecystectomy. Intraoperative time out is one of the strategies where two or more surgeons stop during surgery before dividing any structure in Calot's triangle. COVID-19 pandemic has expanded the horizon of telesurgery, teleconsultation, use of artificial intelligence and robotics in surgical training and execution. Easily available mobile applications like Facebook messenger, WhatsApp and Viber can be used for intraoperative time-out during difficult cholecystectomy with expert surgeon outside the vicinity of theatre. Such tools are cost effective and definitely boost the confidence of surgeons during surgery in case of any complexity, or help in stopping the procedure and in timely referral. Keywords: Cholecystectomy; laparoscopy; telementoring.

Prevalence, Predictors, and Oncologic Outcomes of Pelvic Organ Involvement in Women Undergoing Radical Cystectomy.

CONTEXT.­: In women, radical cystectomy includes removal of the bladder, uterus, fallopian tubes, ovaries, and anterior vaginal wall, yet contiguous extension of urothelial carcinoma to all pelvic organs is rare and routine removal may be unnecessary. OBJECTIVE.­: To study pelvic organ involvement in women at radical cystectomy and investigate oncologic outcomes. DESIGN.­: Women with bladder cancer who underwent radical cystectomy at the Mayo Clinic and University of Toronto (1980-2018) were evaluated. Cancer-specific survival (CSS) was estimated with the Kaplan-Meier method; comparisons were made with the log-rank test. Associations with CSS were evaluated with Cox proportional hazard modeling. RESULTS.­: A total of 70 women with pT4a and 83 with pT3b cancer were studied. Organs involved were vagina (n = 41 of 70; 58.6%), uterus (n = 26 of 54; 48.1%), cervix (n = 15 of 54; 27.8%), fallopian tubes (n = 10 of 58; 17.2%), and ovaries (n = 7 of 58; 12.1%); 22 of 58 patients (37.9%) had >1 organ involved. Of 70 with pT4a cancer, 64 were available for survival analysis by 3 pelvic organ groups: vaginal only, vaginal and/or cervical/uterine, and vaginal and/or cervical/uterine and/or fallopian tubes/ovarian involvement. Three-year CSS for vaginal involvement only was 39%; it was 14% if cervical/uterine involvement, and <1% if fallopian tube/ovarian involvement was included (P = .02). Among 20 women with pT4aN0/Nx and vaginal involvement only, 3-year CSS for vaginal involvement was 50%, whereas among 48 women with pT3bN0/Nx cancer, 3-year CSS was 58%, P = .70. CONCLUSIONS.­: Isolated vaginal involvement should be separated from uterine and/or adnexal extension of urothelial carcinoma at pathologic staging. Direct ovarian extension is rare and routine removal may be unnecessary.

Perioperative and Oncologic Outcomes Associated with Simultaneous Radical Cystectomy and Nephroureterectomy.

OBJECTIVE: To compare the perioperative and oncologic outcomes associated with RCNU to a matched cohort undergoing RC alone. Simultaneous radical cystectomy and nephroureterectomy (RCNU) for synchronous upper tract and bladder urothelial carcinoma is an uncommon procedure. Sparse literature exists comparing outcomes in patients treated with radical cystectomy (RC) alone versus RCNU. METHODS: Adults treated with RCNU for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) between 1980 and 2020 were identified. Patients were matched 2:1 to patients undergoing RC alone for UCB based on age (+/- 5 years), gender, BMI (+/- 5), Charlson Comorbidity Index, pathologic staging (stage ≤pT2 vs >pT2), and receipt of neoadjuvant chemotherapy. Outcomes included overall survival (OS), recurrence free survival (RFS), cancer specific survival (CSS), 30-day complications, length of stay (LOS), operative time, and estimated blood loss (EBL). RESULTS: A total of 39 patients undergoing RCNU were identified and matched to 74 patients undergoing RC. There were no significant differences in LOS, EBL, or 30-day complication rates. Operative time was significantly longer in the RC cohort. OS (HR 0.58, CI 0.35-0.97, P = .036) was significantly better for patients undergoing RC alone, while no significant difference was noted in RFS (HR 0.65, 0.34-1.24) and CSS (HR 0.58, CI 0.31-1.08, P = .08). CONCLUSIONS: Patients undergoing RCNU had significantly lower OS compared to a matched group of patients undergoing RC alone. Perioperative outcomes between the groups did not differ significantly. This data can inform patient counseling for treatment of this rare disease state.

The MIDA-Q Mortality Risk Score: A Quantitative Prognostic Tool for the Mitral Valve Prolapse Spectrum.

BACKGROUND: Mitral valve prolapse (MVP) is responsible for a considerable disease burden but is widely heterogeneous. The lack of a comprehensive prognostic instrument covering the entire MVP spectrum, encompassing the quantified consequent degenerative mitral regurgitation (DMR), hinders clinical management and therapeutic trials. METHODS: The new Mitral Regurgitation International Database Quantitative (MIDA-Q) registry enrolled 8187 consecutive patients (ages 63±16 years, 47% women, follow-up 5.5±3.3 years) first diagnosed with isolated MVP, without or with DMR quantified prospectively (measuring effective regurgitant orifice [ERO] and regurgitant volume) in routine practice of 5 tertiary care centers from North America, Europe, and the Middle East. The MIDA-Q score ranges from 0 to 15 by accumulating guideline-based risk factors and DMR severity. Long-term survival under medical management was the primary outcome end point. RESULTS: MVP was associated with DMR absent/mild (ERO <20 mm2) in 50%, moderate (ERO 20-40 mm2) in 25%, and severe or higher (ERO ≥40 mm2) in 25%, with mean ERO 24±24 mm2, regurgitant volume 37±35 mL. Median MIDA-Q score was 4 with a wide distribution (10%-90% range, 0-9). MIDA-Q score was higher in patients with EuroScore II ≥1% versus <1% (median, 7 versus 3; P < 0.0001) but with wide overlap (10%-90% range, 4-11 versus 0-7) and mediocre correlation (R2 0.18). Five-year survival under medical management was strongly associated with MIDA-Q score, 97±1% with score 0, 95±1% with score 1 to 2, 82±1% with score 3 to 4, 67±1% with score 5 to 6, 60±1% with score 7 to 8, 44±1% with score 9 to 10, 35±1% with score 11 to 12, and 5±4% with MIDA-Q score ≥13, with hazard ratio 1.31 [1.29-1.33] per 1-point increment. Excess mortality with higher MIDA-Q scores persisted after adjustment for age, sex, and EuroScore II (adjusted hazard ratio, 1.13 [1.11-1.15] per 1-point increment). Subgroup analysis showed persistent association of MIDA-Q score with mortality in all possible subsets, in particular, with EuroScore II<1% (hazard ratio, 1.08 [1.02-1.14]) or ≥1% (hazard ratio, 1.11 [1.08-1.13]) and with no/mild DMR (hazard ratio, 1.14 [1.10-1.19]) or moderate/severe DMR (hazard ratio, 1.13 [1.10-1.16], all per 1-point increment with P<0.0001). Nested-model and bootstrapping analyses demonstrated incremental prognostic power of MIDA-Q score (all P<0.0001). CONCLUSIONS: This large, international cohort of isolated MVP, with prospective DMR quantification in routine practice, demonstrates the wide range of risk factor accumulation and considerable heterogeneity of outcomes after MVP diagnosis. The MIDA-Q score is strongly, independently, and incrementally associated with long-term survival after MVP diagnosis, irrespective of presentation, and is therefore a crucial prognostic instrument for risk stratification, clinical trials, and management of patients diagnosed with all forms of MVP.

Strategies in the Management of Pancreatic Ductal Adenocarcinoma Involving Aberrant Right Hepatic Artery Arising From the Superior Mesenteric Artery.

Introduction The prevailing guidelines do not include the involvement of an aberrant right hepatic artery (aRHA) arising from the superior mesenteric artery in classifying borderline resectable pancreatic ductal adenocarcinoma (BR PDAC). Our novel classification aims to distinguish different entities depending on the location and degree of tumor involvement of aRHA and propose a strategy to manage tumor involvement of aRHA in PDAC. Material and methods The patients who underwent pancreaticoduodenectomy (PD) from September 1, 2018, to August 31, 2022 were analyzed retrospectively, and patients with aRHA were included in the study. Depending on the radiological data, arterial involvement of the aRHA was classified into group I with proximal involvement of the aRHA up to 2 cm from its origin in the superior mesenteric artery (SMA) and group II with distal involvement of aRHA beyond 2 cm from its origin in SMA. In addition, the resection margin status was correlated with the technique employed for managing the tumor-involved artery. Results A total of 122 patients underwent PD during the study period. Eight patients were identified to have tumor involvement of the aRHA arising from the SMA. Among the five patients in group I, three patients who had upfront surgery showed R1 resection regardless of periarterial divestment or resection/reconstruction of the involved artery, whereas R0 resection was achieved in the two patients who had neoadjuvant therapy. All patients in group II had R0 resection regardless of receiving neoadjuvant therapy. There were no significant morbidity and mortality in our series. Conclusion The aRHA should be considered in the classification of BR PDAC. Management strategies should be tailored based on the location and the degree of tumor involvement in the aRHA. We advocate neoadjuvant therapy for proximal involvement and upfront surgery for distal involvement of aRHA to achieve good oncological clearance.

Cumulative rehospitalizations and implications for subsequent mortality after first-ever ischemic stroke.

INTRODUCTION: Clinical implications of readmission following initial hospitalization for acute ischemic stroke (AIS) are not known. We examined predictors of readmissions and impact of readmissions on subsequent mortality after first-ever AIS. MATERIALS AND METHODS: Adults aged ≥18 years who survived to discharge after hospitalization for first-ever AIS from 2003 to 2019 were included in the study. For each patient, the overall burden of hospitalizations was measured as total number of hospitalizations and aggregate days spent hospitalized during follow-up. We used Poisson regression to estimate incident rate ratios (IRR) for predictors of re-hospitalization and time-dependent Cox regression to estimate hazard ratios (HR) for mortality. RESULTS: Of 908 AIS survivors, 537 died, 669 had 2,645 readmissions over 4,535 person-years follow-up. Adjusted independent predictors of cumulative readmission inlcuded being white (IRR 1.21, 95% CI 1.03-1.42), dependency on discharge (IRR 1.27, 95% CI 1.17-1.38), cardio-embolism (IRR 1.35, 95% CI 1.18-1.45), smoking (IRR 1.21, 95% CI 1.08-1.35), anemia (IRR 1.40, 95% CI 1.24-1.57), arthritis (IRR 1.20, 95% CI 1.10-1.31), coronary artery disease (IRR 1.34, 95% CI 1.23-1.47), cancer (IRR 1.96, 95% CI 1.64-2.30), chronic kidney disease (IRR 1.36, 95% CI 1.21-1.57), COPD (IRR 1.18, 95% CI 1.04-1.34), depression (IRR 1.50, 95% CI 1.37-1.66), diabetes mellitus (IRR 1.48, 95% CI 1.36-1.48), and heart failure (IRR 1.17, 95% CI 1.03-1.34). Conversely, hyperlipidemia was associated with a lower risk of readmission (IRR 0.79, 95% CI 0.71-0.88). Mortality was significantly increased with each hospitalization and cumulative days spent in hospital. CONCLUSIONS: Among survivors of AIS hospitalization, certain sociodemographic indicators, stroke-specific features, and several key comorbid conditions were associated with increased risk of readmissions, which in turn correlated with increased mortality. Therefore, lifestyle modification and optimal treatment of comorbidities are likely to improve the outcome after AIS.

Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer.

INTRODUCTION AND OBJECTIVES: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. MATERIALS AND METHODS: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher's exact test and postoperative survival using Kaplan-Meier survival curves and Cox regression model. RESULTS: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1+B7-H3+). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06-5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18-6.04, p = 0.019). CONCLUSIONS: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection.

Comparative Performance of Different Respiratory Test Parameters for Detection of Early Respiratory Insufficiency in Patients With ALS.

BACKGROUND AND OBJECTIVES: To compare the performance of different respiratory function testing parameters in a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic. METHODS: Demographics, clinical data, and respiratory testing parameters were abstracted from the medical records of patients who attended a multidisciplinary ALS clinic from 2008 to 2016. We compared the performance of the 3 primary respiratory test parameters used by Medicare for the initiation of noninvasive ventilation (NIV) (forced vital capacity [FVC] < 50% predicted, maximum inspiratory pressure [MIP] < 60 cm H2O, and abnormal overnight pulse oximetry [OvOx]) on how they related to several clinically relevant attributes. RESULTS: Four hundred seventy-six patients were identified who underwent at least 1 respiratory test. Abnormalities of OvOx, MIP, and FVC occurred at a median of 1.6, 1.5, and 3.8 years from disease onset, respectively (p < 0.00001). Patients with bulbar-onset ALS exhibited earlier abnormalities in MIP and FVC than in spinal-onset ALS (p < 0.005). The median survival after an abnormal OvOx, MIP, or FVC test was 1.4, 1.4, and 0.9 years, respectively (p < 0.0001). Using the ALS Functional Rating Score respiratory subscales, at the time of reported respiratory symptoms there were abnormalities in OvOx (60%), MIP (69%), and FVC (19%). Conversely, when respiratory parameter abnormalities preceded reported respiratory symptoms, this occurred with frequencies in OvOx (79%), MIP (42%), or FVC (24%). Four hundred forty-three patients (93.1%) developed at least 1 abnormal respiratory measure meeting Medicare criteria for NIV consideration, but fewer than 50% in our cohort demonstrated NIV use. Improved survival in subjects using NIV was statistically significant in patients with bulbar-onset ALS. DISCUSSION: Abnormalities in OvOx and MIP perform better than FVC at early detection of neuromuscular respiratory weakness in ALS. Initiation of NIV in patients with respiratory insufficiency may improve the overall survival in ALS. In the setting of the COVID-19 pandemic, FVC and MIP have not been routinely performed because of infectious aerosol generation. OvOx, which we now routinely mail to patients' homes, has been used exclusively during the COVID-19 pandemic and allows for continued remote monitoring of the respiratory status of patients with ALS. CLASSIFICATION OF EVIDENCE: This cohort study provides Class III evidence that in people with ALS, OvOx and MIP are valuable respiratory parameters for the detection of early respiratory insufficiency.

Incremental Prognosis by Left Atrial Functional Assessment: The Left Atrial Coupling Index in Patients With Floppy Mitral Valves.

Background Emerging data suggest important prognostic value to left atrial (LA) characteristics, but the independent impact of LA function on outcome remains unsubstantiated. Thus, we aimed to define the incremental prognostic value of LA coupling index (LACI), coupling volumetric and mechanical LA characteristics and calculated as the ratio of left atrial volume index to tissue Doppler imaging a', in a large cohort of patients with isolated floppy mitral valve. Methods and Results All consecutive 4792 patients (61±16 years, 48% women) with isolated floppy mitral valve in sinus rhythm diagnosed at Mayo Clinic from 2003 to 2011, comprehensively characterized and with prospectively measured left atrial volume index and tissue Doppler imaging a' in routine practice, were enrolled, and their long-term survival analyzed. Overall, LACI was 5.8±3.7 and was <5 in 2422 versus ≥5 in 2370 patients. LACI was independently higher with older age, more mitral regurgitation (no 3.8±2.3, mild 5.1±3.0, moderate 6.5±3.8, and severe 7.8±4.3), and with diastolic (higher E/e') and systolic (higher end-systolic dimension) left ventricular dysfunction (all P≤0.0001). At diagnosis, higher LACI was associated with more severe presentation (more dyspnea, more severe functional tricuspid regurgitation, and elevated pulmonary artery pressure, all P≤0.0001) independently of age, sex, comorbidity index, ventricular function, and mitral regurgitation severity. During 7.0±3.0 years follow-up, 1146 patients underwent mitral valve surgery (94% repair, 6% replacement), and 880 died, 780 under medical management. In spline curve analysis, LACI ≥5 was identified as the threshold for excess mortality, with much reduced 10-year survival under medical management (60±2% versus 85±1% for LACI <5, P<0.0001), even after comprehensive adjustment (adjusted hazard ratio, 1.30 [95% CI, 1.10-1.53] for LACI ≥5; P=0.002). Association of LACI ≥5 with higher mortality persisted, stratifying by mitral regurgitation severity of LA enlargement grade (all P<0.001) and after propensity-score matching (P=0.02). Multiple statistical methods confirmed the significant incremental predictive power of LACI over left atrial volume index (all P<0.0001). Conclusions LA functional assessment by LACI in routine practice is achievable in a large number of patients with floppy mitral valve using conventional Doppler echocardiographic measurements. Higher LACI is associated with worse clinical presentation, but irrespective of baseline characteristics, LACI is strongly, independently, and incrementally determinant of outcome, demonstrating the crucial importance of LA functional response to mitral valve disease.

Prevalence and Outcomes of Bicuspid Aortic Valve in Patients With Aneurysmal Sub-Arachnoid Hemorrhage: A Prospective Neurology Registry Report.

Background Intracranial aneurysms are reported in 6%-10% of patients with bicuspid aortic valve (BAV), and routine intracranial aneurysm surveillance has been advocated by some. We assessed the prevalence and features of the most important patient-outcome: aneurysmal sub-arachnoid hemorrhage (aSAH), as compared with controls without aSAH, and tricuspid aortic valve (TAV) with aSAH. Methods and Results Adult patients with accurate diagnosis of aSAH and at least one echocardiogram between 2000 and 2019 were identified from a consecutive prospectively maintained registry of aSAH admissions. Controls without a diagnosis of SAH were age- and sex-matched. BAV prevalence was confirmed echocardiographically. Severity of aSAH was categorized using modified Fisher and World Federation of Neurological Scale. Neurologic outcome was assessed using modified Rankin score. A total 488 aSAH cases and 990 controls were identified and BAV status was confirmed. Prevalence of BAV in patients with aSAH was 1.2% (6/488) versus 3.5% (35/990) in controls, P=0.01. BAV+aSAH were noted to be younger than TAV+aSAH (56±11 versus 68±14; P=0.03) with smaller aneurysms (5±2 versus 7±4; P=0.31). The severity of aSAH was lesser in BAV+aSAH than TAV (modified Fisher grade>2 50% versus 74%; P=0.19, World Federation of Neurological Scale grade>3 17% versus 36%; P=0.43). BAV+aSAH had less severe neurologic disability (modified Rankin score 3%-6 33% versus 49% in TAV; P=0.44) and comparable in-hospital mortality rates (P=0.93). BAV had lower odds for aSAH on multivariate analysis (odds ratio 0.23[CI 0.08-0.65]; P=0.01). Conclusions Prevalence of BAV was 3 times lower in the aSAH registry than in controls without aSAH. BAV+aSAH had clinically smaller aneurysms, clinically smaller bleeds, and better neurologic outcome as compared with TAV+aSAH, which needs to be confirmed in larger studies. These findings argue against routine surveillance for intracranial aneurysms in patients with BAV without aortic coarctation.

Magnetic resonance imaging (MRI) helps differentiate renal cell carcinoma with sarcomatoid differentiation from renal cell carcinoma without sarcomatoid differentiation.

PURPOSE: The aim of the present study is to identify predictive imaging findings and construct a diagnostic model for differentiating renal cell carcinoma (RCC) with and without sarcomatoid dedifferentiation (sRCC and non-sRCC). METHODS: This study is a single-center retrospective study. All patients had magnetic resonance imaging (MRI) with gradient-echo T1-weighted images, single-shot T2-weighted images (T2WI), and enhanced nephrographic phase images. Forty pathologically confirmed sRCCs and 80 non-sRCCs were included in this study. Control cases were selected by matching the tumor diameter and the year of MRI. Two radiologists independently evaluated the following findings: growth pattern, presence of low-intensity area on T2WI in the tumor (T2LIA), presence of non-enhancing area, local tumor stage, and presence of regional lymphadenopathy. Two radiologists measured the diameter of the tumor, T2LIA, and the non-enhancing area. Multivariable logistic regression analysis was used to identify independent predictive factors for differentiating sRCC from non-sRCC. Selected variables were entered in the logistic regression model, and the area under the curve (AUC) was calculated for each reader with 95% confidence intervals (CIs). RESULTS: Larger T2LIA-to-tumor diameter ratio, regional lymphadenopathy, and local tumor stage 4 were associated with sRCC, and selected for the subsequent construction of a logistic regression model. With this model, the AUCs were 0.76 (95% CI, 0.66-0.85) and 0.70 (95% CI, 0.59-0.81) for prediction of sRCC. CONCLUSION: In conclusion, larger T2LIA-to-tumor diameter ratio, regional lymphadenopathy, and local tumor stage 4 are predictive findings of sRCC. As a result, the model constructed using these findings demonstrated a moderate degree of diagnostic accuracy.

Automated Global Longitudinal Strain Exhibits a Robust Association with Death in Asymptomatic Chronic Aortic Regurgitation.

BACKGROUND: Whether automated left ventricular global longitudinal strain (LVGLS) is associated with outcomes in patients with asymptomatic aortic regurgitation (AR) is unknown. The aim of this study was to explore the impact of automated LVGLS on survival and compare it with conventional left ventricular (LV) parameters in patients with chronic asymptomatic AR. METHODS: LVGLS (presented as an absolute value) was measured using fully automated two-dimensional strain software in consecutive patients with isolated chronic moderate to severe or greater AR between 2004 and 2020; the incremental value of LVGLS was assessed. Limited correction of endocardial border tracking was performed if needed. RESULTS: Of 550 asymptomatic patients (mean age, 60 ± 17 years; 86% men), average LVGLS was 17 ± 3% (first and second tertiles, 15.8% and 18.5%). In 16% of cases, tracking border was partially corrected; average time for analysis was 25 ± 5 sec. At a median of 4.8 years (interquartile range, 1.5-9.9 years), 87 patients had died (19 died after aortic valve surgery). Separate multivariable models adjusted for age, sex, Charlson index, AR severity, and time-dependent aortic valve surgery demonstrated that LV ejection fraction (hazard ratio [HR] per 10%, 0.9), LV end-systolic volume index (LVESVi; HR per 5 mL/m2, 1.08) and LVGLS (HR per unit, 0.87) were independently associated with death (P ≤ .018 for all); however, LVGLS remained statistically significant (HR: 0.86-0.9; P ≤ .007) when compared head-to-head with LV ejection fraction, LVESVi, and LV end-systolic dimension index. The association of LVGLS and mortality was consistent across all subgroups (P for interaction ≥ .08 for all). Spline curves showed that continuous risk for death rose at LVGLS < 15%. Those with LVGLS < 15% had a 2.6-fold risk for death (95% CI, 1.54-4.23) while those with LVGLS < 15% plus LVESVi ≥ 45 mL/m2 had 3.96-fold risk (95% CI, 1.94-8.03). CONCLUSIONS: In this large cohort of asymptomatic patients with moderate to severe or greater AR, automated LVGLS was feasible, efficient, and independently associated with death in head-to-head comparisons with conventional LV ejection fraction, LV end-systolic dimension index, and LVESVi. An automated LVGLS threshold of <15% alone or combined with LVESVi ≥ 45 mL/m2 was significantly associated with increased mortality risk and may be considered in early surgery decision-making.