Effect of Socialization on Alzheimer's Disease During the COVID-19 Pandemic.

Age is the strongest risk factor for Alzheimer's disease, a neurodegenerative disease where beta-amyloid plaques accumulate in the brain. Elderly individuals, especially those in nursing homes, were burdened by social isolation during the COVID-19 pandemic. The purpose of this literature review is to describe the effectiveness of social engagement and how combating isolation can have a neuroprotective effect on individuals at risk for Alzheimer's disease. We conducted a search in PubMed examining articles from 2010 to 2023 that discussed the impact of socialization on Alzheimer's disease, particularly during the COVID-19 pandemic. Our search terms were "Alzheimer's Disease + Socialization," "Social Isolation + Alzheimer's Disease," "Alzheimer's Disease + COVID-19," "COVID-19 + Social Isolation," and "Social Interventions + Alzheimer's Disease." Inclusion criteria consisted of patients ages 60 and older with Alzheimer's disease, mention of social isolation or engagement, and any relationship between COVID-19 and Alzheimer's disease. Exclusion criteria were defined as other dementias, non-social interventions, and the effects of different viruses on Alzheimer's disease. After the screening process, 30 articles were included, along with six articles that were suitable to the topic. Of the 36 total articles, 19 focused on an intervention involving socialization; eight explored the effect of social isolation during COVID-19 on patients with Alzheimer's disease; five articles examined social isolation as a risk factor for dementia; and four articles discussed the effect of socialization on Alzheimer's disease. A few studies reported that having a large social network can improve cognition and mood for patients with Alzheimer's disease. Studies reported that interventions such as volunteering, video calls, group art classes, animal interactions, and others produced positive outcomes in Alzheimer's patients, but not all were statistically significant. Our review found a consistent association between a socially integrated lifestyle and a decreased incidence of early-onset dementia. Although not all interventions were solely social, a strong social structure remained at the core of a healthy aging process.

Endoscopic Management of Gastric Band Erosion: a Systematic Review and Meta-Analysis.

BACKGROUND: Gastric band erosion may be seen in up to 3% of patients. Endoscopic intervention has become increasingly utilized due to its minimally invasive nature. The purpose of this study was to perform a systematic review and meta-analysis to examine the role of endoscopic removal for eroded gastric bands. METHODS: Individualized search strategies were developed for PubMed, EMBASE, Web of Science, and Cochrane Library databases in accordance with PRISMA and MOOSE guidelines. Outcomes included technical success, clinical success, procedure duration, adverse events, and surgical conversion. Pooled proportions were analyzed using random effects models. Heterogeneity and publication bias was assessed with I2 statistics and funnel plot asymmetry using Egger and Begg tests. Meta-regression was also performed comparing outcomes by endoscopic tools. RESULTS: Ten studies (n=282 patients) were included in this meta-analysis. Mean age was 40.68±7.25 years with average duration of band placement of 38.49±19.88 months. Pre-operative BMI was 42.76±1.06 kg/m2 with BMI of 33.06±3.81 kg/m2 at time of band erosion treatment. Endoscopic removal was attempted in 240/282 (85.11%) of cases. Pooled technical and clinical success of the endoscopic therapy was 86.08% (95% CI: 79.42-90.83; I2=28.62%) and 85.34% (95% CI: 88.70-90.62; I2=38.56%), respectively. Mean procedure time for endoscopic removal was 46.47±11.52 min with an intra-operative adverse event rate of 4.15% (95% CI: 1.98-8.51; I2=0.00%). Post-procedure-associated adverse events occurred in 7.24% (CI: 4.46-11.55; I2=0.00%) of patients. Conversion to laparotomy/laparoscopy occurred in 10.54% (95% CI: 6.12-17.54) of cases. CONCLUSION: Endoscopic intervention is a highly effective and safe modality for the treatment of gastric band erosion.

Social Determinants of Health Impacting Access to Renal Dialysis for Racial/Ethnic Minorities.

Although widespread, the burden of disease presented by chronic kidney disease (CKD) is not equally distributed among all demographics. Examining the social determinants of health (SDOH) that relate to barriers to renal dialysis care in CKD can help to prevent future disparities. There has not been a study addressing the social factors that create barriers to care for ethnic minority patients with CKD. The aim of this scoping review is to address the SDOH that affects access to renal dialysis for ethnic minority patients in the United States. This study was based on the protocol published by the Joanna Briggs Institute. A total of 349 studies were identified from PubMed, EBSCOhost, and Embase. Each article was screened against population, concept, and context criteria in order to be considered for inclusion. The population was determined to be adults of all genders from underrepresented minority populations. The selected concept was SDOH. The context of this study was the United States population. From the articles selected by the search criteria, neighborhood of residence, mental health care access, glomerular filtration rate (GFR) methodology, socioeconomic status (SES), language barriers, immigration status, and military rank were identified as SDOH affecting access to renal dialysis care. While this study identified four social determinants, more research is needed for the investigation of other possible SDOH contributing to disparities related to CKD and access to renal dialysis care.

Persistent Heart Failure Despite Medical Therapy Leading to a Diagnosis of Cardiac Amyloidosis.

Cardiac amyloidosis is restrictive cardiomyopathy, commonly classified as either light-chain amyloidosis (AL) or transthyretin amyloidosis (ATTR), which can be further subdivided into wild-type (systemic senile amyloidosis) and hereditary ATTR amyloidosis. Advanced-stage, silent, and clinically undiagnosed amyloidosis has a poor prognosis, with a survival rate of six months and up to five years. We present a 72-year-old female with a past medical history of heart failure, with preserved ejection fraction, atrial fibrillation, systemic lupus erythematosus (SLE), and stage 3b chronic kidney disease, who presented with persistent shortness of breath, lower extremity pitting edema, jugular venous distension, and dyspnea despite optimal medical therapy. The patient was diagnosed with preserved heart failure in the past and was on guideline-directed medical therapy for over five years with no history of cardiac disease in the family. The patient's previous echocardiogram revealed an ejection fraction of 65%. In order to determine the etiology of the patient's cardiomyopathy, she underwent cardiac magnetic resonance imaging (CMR), monoclonal gammopathy testing, and a Technetium pyrophosphate (99mTc-PYP) scintigraphy, of which the latter two were unrevealing. The CMR revealed increased wall thickness and multiple segments of midmyocardial to subendocardial late gadolinium enhancement, suggestive of infiltrative disease. Due to inconclusive testing, the patient underwent an endomyocardial biopsy and was determined to have wild-type, systemic senile amyloidosis, which held a poor prognosis. The patient was started on tafamidis, a new Food and Drug Administration (FDA)-approved therapy for systemic senile amyloidosis, and was discharged on the new medication, with frequent follow-up visits scheduled. Current treatment guidelines for cardiac amyloidosis include loop diuretics and spironolactone. Medications such as beta-blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers are not clinically effective. There are currently new medications on the horizon, such as tafamidis, which stabilizes the transthyretin tetramer and reduces the formation of amyloid. This case highlighted that patients who have persistent symptoms of heart failure, despite guideline-directed medical therapy, and without a history of genetic cardiac conditions, may also have a diagnosis of cardiac amyloidosis. Cardiac amyloidosis is often misdiagnosed or diagnosed late in the disease course; therefore, there is a need for increasing awareness of early diagnosis and treatment, including new FDA-approved medications for a better chance of survival.

Bentall versus valve-sparing aortic root replacement for root pathology with moderate-to-severe aortic insufficiency: a propensity-matched analysis.

OBJECTIVES: To examine short- and long-term outcomes of patients with moderate-to-severe aortic insufficiency (AI) undergoing either a Bentall aortic root replacement (ARR) or valve-sparing root replacement (VSRR). METHODS: A two-centre retrospective database of patients undergoing ARR from 2004 to 2021 was reviewed. Patients <18 years old were excluded. A total of 1527 adult patients underwent Bentall ARR (n = 1150, 75%) or VSRR (n = 377, 25%). Propensity score matching based on preoperative comorbidities was used and 195 matched pairs were identified. Perioperative outcomes, reoperation rates, recurrence of AI and long-term survival were evaluated. RESULTS: ARR patients had more concomitant ascending aortic replacement (35% vs 20%, P = 0.002) and shorter cardiopulmonary bypass (189 vs 233 min, P < 0.0001) and aortic cross-clamp (170 vs 204 min, P < 0.0001) times than the VSRR group. Postoperatively, outcomes were similar between groups, including stroke (3% vs 2%) and in-hospital mortality (1.5% vs 2.1%), all P > 0.05. Indications for and rates of reoperation (4% vs 5%, P = 0.62) of the aortic valve and proximal aorta were similar between ARR and VSRR groups with reoperations occurring a mean of 3.2 years after initial root replacement. The ARR group had less moderate-to-severe AI than the VSRR group (1.6% vs 14%, P = 0.002) a mean of 3 years after surgery. Ten-year survival was similar between ARR (84%) and VSRR (82%) (P = 0.69) groups. CONCLUSIONS: Both ARR and VSRR can be performed with acceptable short- and long-term outcomes in patients with moderate-to-severe AI.

Transition from standard robotic prostatectomy to Retzius-sparing prostatectomy: feasibility and early outcomes.

BACKGROUND AND OBJECTIVE: Retzius-sparing robotic-assisted radical prostatectomy (rsRARP) has gained popularity due to superior early continence outcomes compared to standard robotic prostatectomy (sRARP). We evaluate the results of a single surgeon who transitioned from sRARP to rsRARP and compare oncologic and functional outcomes. METHODS: We retrospectively reviewed all prostatectomies performed by a single surgeon between June 2018 and October 2020. Perioperative, oncologic, and functional data were collected and analyzed. Patients who underwent sRARP were compared with those who underwent rsRARP. RESULTS: Both groups contained 37 consecutive patients each. Preoperative patient characteristics and biopsy results were similar between the two groups. Perioperative outcomes were significant for longer operative room time and higher proportion of T3 tumors in the rsRARP group. Thirty-day complication and readmission rates were similar between groups. There was no difference in early oncologic outcomes, including positive surgical margin rate, biochemical recurrence, and need for adjuvant or salvage treatments. The time to urinary continence and immediate continence rate was superior in the rsRARP group. CONCLUSIONS: The Retzius-sparing approach can be safely adopted by surgeons experienced in sRARP without compromising early oncologic outcomes and with the benefit of improved early continence recovery.

Endoscopic retrograde cholangiopancreatography outcomes in inflammatory bowel disease patients: a 12-year analysis of a national database.

BACKGROUND: Despite inflammatory bowel disease's (IBD) association with hepatobiliary disorders and the use of endoscopic retrograde cholangiopancreatography (ERCP) for both diagnostic and therapeutic evaluation of these diseases, it remains a poorly studied area within the literature. The purpose of this study is to examine the effect of IBD on the occurrence of adverse events (AE) pertaining to ERCP. METHODS: This project utilized the National Inpatient Sample (NIS) database, the largest inpatient database in the USA. All patients 18 years or older with and without IBD undergoing ERCP were identified from 2008 to 2019. Post-ERCP AEs were analyzed using multivariate logistic or linear regression controlling for age, race, and existing comorbidities using the Charlson comorbidity index (CCI). RESULTS: There was no difference in post-ERCP pancreatitis (PEP) or mortality. IBD patients were also found to have a lower risk of bleeding and decreased length of stay (LOS) despite adjustment for comorbidities. They also underwent less sphincterotomies when compared to the non-IBD cohort. Subgroup analysis between ulcerative colitis (UC) and Crohn's disease (CD) did not find any significant differences in outcomes. CONCLUSION: To our knowledge, this is the largest study to date evaluating ERCP outcomes in IBD patients. After adjustment of co-variates, there was no difference in the occurrence of PEP, infections, and perforation. IBD patients were less likely to experience post-ERCP bleeding and mortality and had shorter LOS which may be due to the decreased frequency of sphincterotomy in this population.

Opioid Requirement After Anterior Cruciate Ligament Surgery: Opioid Use After Anterior Cruciate Ligament Surgery Is Low With a Multimodal Approach, and Fifteen Oxycodone 5-mg Tablets Are Sufficient.

Purpose: To prospectively determine opioid consumption in patients undergoing anterior cruciate ligament (ACL) repair and reconstruction and to develop evidence-based prescription guidelines following ACL surgery. Methods: This multicenter prospective study enrolled patients undergoing ACL reconstruction and repair. Subject demographics and opioid prescriptions were recorded at enrollment. All patients were given education on opiate use and followed the same perioperative, multimodal analgesic regimen. Following surgery, patients were given postoperative "pain journals" to document visual analog scale pain scores and daily opioid consumption for the first 7 postoperative days and on postoperative visit at 14 days. Results: In total, 50 patients were included in this analysis between the ages of 14 and 65 years. Patients were prescribed a median of 15 oxycodone 5-mg pills and consumed a median of 2 pill postoperatively (range 0-19 pills). 38% of patients consumed 0 opioid pills, 74% of patients consumed ≤5 opioid pills, and 96% of patients consumed ≤15 opioid pills. Patients reported a mean daily visual analog scale value of 2.8 of 10; mean satisfaction with pain management was high at 4.1/5 on a Likert satisfaction score. Overall, patients consumed a mean 34% of their opioid prescriptions, leaving 436 opioid pills not consumed. Conclusions: This study suggests that current expert panels may be recommending an excessive volume of opioids. Based on our findings, we recommend that patients be prescribed no more than 15 Oxycodone 5-mg tablets following ACL surgery. Despite this lower volume prescription, mean pain scores remained below 3 of 10, patient satisfaction with pain control remained high, and 66% of opiate medication prescribed was not used. Level of Evidence: II, prospective prognostic cohort investigation.

Bioprosthetic Pulmonary Valve Dysfunction in Congenital Heart Disease.

BACKGROUND: We aim to identify the incidence and timing of dysfunction and failure of stented bioprosthetic valves in the pulmonary position in congenital heart disease patients. METHODS: A total of 482 congenital heart disease patients underwent 484 stented bioprosthetic pulmonary valve implantations between 2008 and 2018. There were 164 porcine valves (Porcine) and 320 bovine pericardial valves (Pericardial) implanted. Primary endpoints were survival, valve dysfunction, and valve failure. RESULTS: Pericardial valves were implanted in older patients (22.0, interquartile range [IQR] 14-33 vs 16.0, IQR 11-23 years, P < 0.001). Five-year survival (96.7% vs 97.9%) for the Pericardial and Porcine groups, respectively, were similar, P > 0.05. Forty-six (34%) Porcine and 75 (27%) Pericardial group patients met criteria for valve dysfunction at a median echocardiographic follow-up time of 7.43 years (IQR 4.1-9.5 years) and 3.26 years (IQR 1.7-4.7 years), respectively. More Pericardial group patients suffered from at least mild late PR while late median peak gradient was higher in the Porcine group, P < .001 for both. Risk factors for valve dysfunction included decreasing patient age for the entire cohort (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.00-1.04, P = .015) and lack of anticoagulation at discharge for the Porcine group (HR 3.06, 95% CI 1.03-9.10, P = .044) but not the Pericardial group. Five-year cumulative incidence of dysfunction was 39% for the Pericardial group and 17% for the Porcine group. CONCLUSIONS: Porcine stented and bovine pericardial stented valves can be implanted in the pulmonary position in all age groups safely. However, despite similar rates of valve failure, bovine pericardial stented valves have a higher incidence of valve dysfunction at mid-term follow-up.

True redo-aortic root replacement versus root replacement after any previous surgery.

Objective: The impact of previous aortic root replacement (True-Redo) versus any previous operation (Any-Redo) on outcomes after reoperative aortic root replacement (redo-ROOT) is largely unknown. In this first multi-institutional study, the clinical impact True-Redo versus Any-Redo in the setting of redo-ROOT was reviewed. Methods: From 2004 to 2021, 822 patients underwent redo-ROOT at 2 major academic centers: 638 Any-Redo and 184 True-Redo. Matching based on preoperative demographics and concomitant operations resulted in 174 matched pairs. An independent risk factor analysis was performed to determine risk factors for early and late mortality. Results: Patients in the True-Redo group were younger, at 49.9 ± 15.1 versus 55.3 ± 14.7 years, P < .001. Concomitant operations were largely similar between the 2 groups, P > .05. Median cardiopulmonary bypass time (P < .001) and aortic crossclamp time (P = .03) were longer for True-Redo group. In-hospital mortality was 13% (109) and was without significant difference between groups, P = .41. Ten-year survival was 78% versus 76% for True-Redo versus Any-Redo groups respectively, P = .7. Landmark survival analysis at 4 years' postoperatively on the matched groups found that patients in the True-Redo group had improved survival outcomes (P = .046). Risk factors of in-hospital mortality consisted of older age (P < .0001), lower ejection fraction (P = .02), and male patient (P = .0003). Conclusions: Clinical outcomes following redo-ROOT are excellent. Performance of a True-Redo-ROOT does not result in worse in-hospital morbidity or mortality and has improved survival benefit at midterm follow-up when compared with patients in the Any-Redo group. The decision to perform a redo-ROOT must be taken seriously and must be individualized in a patient-specific manner for optimal outcomes.

Presentation of Sjogren Syndrome as Nodular Pulmonary Amyloidosis.

Sjogren syndrome is an autoimmune disorder that leads to dryness in the eyes and mouth. Nodular pulmonary amyloidosis is a localized amyloid deposition pathology commonly seen with monoclonal lymphoproliferative disorders. We present a patient who came in with dyspnea and was found to have nodular pulmonary amyloidosis on biopsy. Commonly associated lymphoproliferative pathologies were ruled out and on further workup, the patient was found to have Sjogren syndrome. This case demonstrates pulmonary nodular amyloidosis as a rare presentation of Sjogren syndrome in the setting of relatively well-controlled symptoms. Detection of pulmonary nodular amyloidosis should prompt evaluation of associated conditions such as malignancy and autoimmune disorders to guide further management.

Thrombotic Thrombocytopenic Purpura After Ad6.COV2.S Vaccination.

Thrombotic thrombocytopenic purpura (TTP) is caused by the deficiency of ADAMTS13, a von Willebrand factor cleaving protease, which results in thrombotic microangiopathy. It is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis leading to organ damage. It has an extremely high mortality rate if left untreated, making early diagnosis and treatment of the utmost importance. We report a case of TTP that developed after vaccination with Ad26.COV2.S COVID vaccine. We present a case of a 50-year-old African American female who presented with dyspnea one week after receiving the first dose of Ad26.COV2.S vaccine. Initial labs showed anemia, thrombocytopenia, and markers of intravascular hemolysis. The suspicion for thrombotic thrombocytopenic syndromes (TTS), vaccine-induced thrombotic thrombocytopenia (VITT), TTP, and Immune thrombocytopenic purpura (ITP) was high based on the history and laboratory results. Computed tomography (CT) of the chest and ultrasound of bilateral lower extremities did not show any evidence of thrombosis. The absence of thrombosis in the presence of a high PLASMIC score increased the suspicion of TTP over the other differentials. Diagnosis of TTP was confirmed when the ADAMTS13 level was low with an elevated autoantibody inhibitor level. The patient underwent treatment with corticosteroids, plasmapheresis, and rituximab with improvement in symptoms and platelet count. TTP and VITT are the possible differential diagnosis for a patient presenting with anemia, thrombocytopenia, and signs of hemolysis after vaccination with Ad26.COV2.S. It is necessary to differentiate these two clinical entities as the management varies based on the diagnosis.

Pharmacomechanical Catheter-Directed Thrombolysis With the Bashir Endovascular Catheter for Acute Pulmonary Embolism: The RESCUE Study.

BACKGROUND: Catheter-directed thrombolysis (CDT) has been associated with rapid recovery of right ventricular (RV) function. The Bashir catheter was developed for enhanced thrombolysis in large vessels such as the pulmonary arteries (PAs) with lower doses of tissue plasminogen activator (tPA). OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of tPA infused using a pharmacomechanical (PM) CDT device called the Bashir endovascular catheter in patients with intermediate-risk acute pulmonary embolism (PE). METHODS: Patients with symptoms of acute PE with computed tomographic evidence of RV dilatation were enrolled. The Bashir catheter was used to deliver 7 mg tPA into each PA over 5 hours. The primary efficacy endpoint was the core laboratory-assessed change in computed tomographic angiography-derived RV/left ventricular (LV) diameter ratio at 48 hours, and the primary safety endpoint was serious adverse events (SAEs) including major bleeding at 72 hours. RESULTS: At 18 U.S. sites, 109 patients were enrolled. The median device placement time was 15 minutes. At 48 hours after PM-CDT, the RV/LV diameter ratio decreased by 0.56 (33.3%; P < 0.0001). PA obstruction as measured by the refined modified Miller index was reduced by 35.9% (P < 0.0001). One patient (0.92%) had 2 SAEs: a retroperitoneal bleed (procedure related) and iliac vein thrombosis (device related). Two other procedure-related SAEs were epistaxis and non-access site hematoma with anemia. CONCLUSIONS: PM-CDT with the Bashir endovascular catheter is associated with a significant reduction in RV/LV diameter ratio and a very low rate of adverse events or major bleeding in patients with intermediate-risk acute PE. The notable finding was a significant reduction in PA obstruction with low-dose tPA. (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden [RESCUE]; NCT04248868).

Perioperative and long-term outcomes of Ross versus mechanical aortic valve replacement.

BACKGROUND: The ideal aortic valve replacement strategy in young- and middle-aged adults remains up for debate. Clinical practice guidelines recommend mechanical prostheses for most patients less than 50 years of age undergoing aortic valve replacement. However, risks of major hemorrhage and thromboembolism associated with long-term anticoagulation may make the pulmonary autograft technique, or Ross procedure, a preferred approach in select patients. METHODS: Data were retrospectively collected for patients 18-50 years of age who underwent either the Ross procedure or mechanical aortic valve replacement (mAVR) between January 2000 and December 2016 at a single institution. Propensity score matching was performed and yielded 32 well-matched pairs from a total of 216 eligible patients. RESULTS: Demographic and preoperative characteristics were similar between the two groups. Median follow-up was 7.3 and 6.9 years for Ross and mAVR, respectively. There were no early mortalities in either group and no statistically significant differences were observed with respect to perioperative outcomes or complications. Major hemorrhage and stroke events were significantly more frequent in the mAVR population (p < .01). Overall survival (p = .93), freedom from reintervention and valve dysfunction free survival (p = .91) were equivalent. CONCLUSIONS: In this mid-term propensity score-matched analysis, the Ross procedure offers similar perioperative outcomes, freedom from reintervention or valve dysfunction as well as overall survival compared to traditional mAVR but without the morbidity associated with long-term anticoagulation. At specialized centers with sufficient expertize, the Ross procedure should be strongly considered in select patients requiring aortic valve replacement.

Using Intraoperative Portable CT Scan to Minimize Reintervention Rates in Percutaneous Nephrolithotomy: A Prospective Trial.

Background and Purpose: More than 40% of patients undergoing percutaneous nephrolithotomy (PCNL) are left with residual stone fragments and often require secondary procedures. Portable CT (PCT) technology allows surgeons to obtain intraoperative cross-sectional imaging, identify and extract residual stones immediately, and thereby reduce the need for subsequent procedures. This prospective trial evaluates how incorporation of PCT during PCNL affects perioperative outcomes. Patients and Methods: We prospectively enrolled eligible patients undergoing initial PCNL for this trial (n = 60), which entailed a single intraoperative CT abdomen and ipsilateral antegrade ureteroscopy when the surgeon felt stone treatment was visually complete. If residual fragments were identified, the surgeon continued nephroscopy to find and remove them; if not, the procedure was concluded. These patients were compared with a retrospective cohort (n = 174) who underwent initial PCNL with postoperative imaging performed the following day. Results: The two cohorts had similar demographic properties and stone characteristics, and location of percutaneous access. In the prospective arm, 50% of intraoperative PCT scans identified residual fragments, prompting continuation of surgery to remove them. This cohort had significantly higher stone-free rate (82% vs 36%, p < 0.01), lower rate of planned reintervention (7% vs 32%, p < 0.01), lower rate of urgent presentation with ureteral obstruction (0% vs 7%, p = 0.04), lower total CT-based effective radiation dose (8.4 mSv vs 14.6 mSv, p < 0.01), and shorter length of stay (2.3 days vs 3.5 days, p < 0.01) when compared with the retrospective cohort that did not use intraoperative PCT. Conclusions: Obtaining an intraoperative PCT scan during PCNL can substantially improve perioperative outcomes. Further evaluation of this modality through a randomized controlled trial is warranted. Clinical Trial Registration Number: NCT04556396.

Four versus 3 Cycles of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Implications for Pathological Response and Survival.

PURPOSE: The ideal number of neoadjuvant chemotherapy (NAC) cycles for muscle-invasive bladder cancer is uncertain with 3 to 4 representing the standard of care (SOC). We compared ypT0 rates and survival between patients receiving 4 versus 3 cycles of NAC with evaluation of chemotherapy-related toxicity for correlation with tumor chemosensitivity and pathological response. MATERIALS AND METHODS: Patients receiving NAC followed by radical cystectomy for cT2-4N0M0 urothelial carcinoma from 2 institutions were included. Primary study groups included 4 cisplatin-based NAC cycles, 3 cisplatin-based NAC cycles, and nonSOC NAC (1-2 cycles or noncisplatin-based) to compare ypT0/≤ypT1 rates and survival. A cohort of patients not receiving NAC was included for pathological reference. RESULTS: Of 693 total patients, 318 (45.9%) received NAC. ypT0 and ≤ypT1 rates were 42/157 (26.8%) and 86/157 (54.8%) for 4 cycles, 38/114 (33.3%) and 71/114 (62.3%) for 3 cycles, and 6/47 (12.8%) and 13/47 (27.7%) for nonSOC (p=0.03 and p <0.01, respectively). Pathological response appeared higher among patients receiving 3 cycles due to toxicity (ypT0: 29/77 [37.7%]; ≤ypT1: 51/77 [66.2%]) but did not reach statistical significance. Toxicities leading to treatment modifications were thrombocytopenia (32.1%), neutropenia (27.2%), renal insufficiency (22.2%), and constitutional symptoms (18.5%). NonSOC patients had lower Kaplan-Meier survival (cT2-cT4N0M0: log-rank p=0.07; cT2N0M0: log-rank p=0.02). There were no statistically significant differences in survival between 4 and 3 cycles (HR 1.00 [95% CI 0.57-1.74], p=0.99). CONCLUSIONS: Patients completing 3 cycles of cisplatin-based NAC have similar pathologic response and short-term survival compared to 4 cycles. Further evaluation of patients experiencing toxicity as a potential marker of tumor chemosensitivity is needed.