Adjuvant Gemcitabine Plus Cisplatin and Chemoradiation in Patients With Gallbladder Cancer: A Randomized Clinical Trial.

Importance: There is limited evidence with regard to the benefit of adjuvant chemotherapy chemoradiotherapy in resected gallbladder cancers (GBCs). Objective: To establish a baseline survival rate for operated GBCs in patients receiving either gemcitabine plus cisplatin (GC) or capecitabine and capecitabine concurrent with chemoradiation (CCRT). Design, Setting, and Participants: The GECCOR-GB study was a multicenter, open-label, randomized phase 2 noncomparator "pick the winner" design trial of adjuvant GC and CCRT in patients with resected histologically confirmed adenocarcinoma or adenosquamous carcinoma of the gallbladder, (stage II/III) with no local residual tumor (R0) or microscopic residual tumor (R1). The study was carried out in 3 tertiary cancer institutions in India. Patients 18 years or older with adequate end-organ functions, and Eastern Cooperative Oncology Group Performance Status of 1 or lower between May 2019 and February 2022 were enrolled. The cutoff date for data analysis was February 28, 2023. Interventions: Patients were randomized 1:1 to receive either GC every 3 weeks (maximum of 6 cycles) or CCRT comprising capecitabine with concurrent chemoradiation (capecitabine concurrent with radiotherapy) sandwiched between capecitabine chemotherapy. Main Outcomes and Measures: The primary outcome was disease-free survival (DFS) at 1 year in randomized patients. This study was conducted as 2 parallel, single-stage phase 2 clinical trials. Within each treatment arm, a 1-year DFS rate of less than 59% was considered as insufficient activity, whereas a 1-year DFS rate of 77% or higher would be considered as sufficient activity. Results: With a median follow-up of 23 months, 90 patients were randomized, 45 in each arm. Overall, there were 31 women (69%) and 14 men (31%) in the GC arm with a mean (range) age of 56 (33-72) years and 34 women (76%) and 11 men (24%) in the CCRT group with a mean (range) age of 55 (26-69) years. In the GC and CCRT arms, 1-year DFS and estimated 2-year DFS was 88.9% (95% CI, 79.5-98.3) and 74.8% (95% CI, 60.4-89.2), and 77.8% (95% CI, 65.4-90.2) and 74.8% (95% CI, 59.9-86.3), respectively. Completion rates for planned treatment was 82% in the GC arm and 62% in the CCRT arm. Conclusions and Relevance: In this randomized clinical trial, GC and CCRT crossed the prespecified trial end points of 1-year DFS in patients with resected stage II/III GBCs. The results set a baseline for a larger phase 3 trial evaluating both regimens in operated GBCs. Trial Registration: ClinicalTrials.gov Identifier: CTRI/2019/05/019323I.

Improving Patient Outcomes Using Measures to Increase Discharge Rates to Home.

Background Post-acute care (PAC) centers are facilities used for recuperation, rehabilitation, and symptom management in an effort to improve the long-term outcomes of patients. PAC centers include skilled nursing facilities, inpatient rehabilitation facilities, and long-term care hospitals. In the 1990s, Medicare payment reforms significantly increased the discharge rates to PAC centers and subsequently increased the length of stay (LOS) among these patient populations. Over the last several years, there have been national initiatives and multidisciplinary approaches to improve safe discharge rates to home. Multiple studies have shown that patients who are discharged to home have decreased rates of 30-day readmissions, reduced short-term mortality, and an improvement in their activities of daily living.  Objectives This study aimed to investigate how multidisciplinary approaches could improve a single institution's discharge rates to home. In doing so, we aim to lower hospital readmission rates, hospital length of stay, morbidity and mortality rates, and healthcare-associated costs. Methods A retrospective single-institution cohort study was implemented at Jersey Shore University Medical Center (JSUMC). Data from January 2015 to December 2019 served as the control period, compared to the intervention period from January 2020 to January 2024. Patients were either admitted to JSUMC teaching faculty, hospitalists, or "others," which is composed of various medical and surgical subspecialists. Interventions performed to improve home discharge rates can be categorized into the following: physician education, patient education, electronic medical record (EMR) initiatives, accountability, and daily mobility initiatives. All interventions were performed equally across the three patient populations. The primary endpoint was the proportion of patients discharged to home. Results There were 190,699 patients, divided into a pre-intervention group comprising 98,885 individuals and a post-intervention group comprising 91,814 patients. Within the pre-intervention group, the faculty attended to 8,495 patients, hospitalists cared for 39,145 patients, and others managed 51,245 patients. In the post-intervention period, the faculty oversaw 8,014 patients, hospitalists attended to 35,094 patients, and others were responsible for 48,706 patients. After implementing a series of multidisciplinary interventions, there was a significant increase in the proportion of patients discharged home, rising from 74.9% to 80.2% across the entire patient population. Specifically, patients under the care of the faculty experienced a more substantial improvement, with a discharge rate increasing from 73.6% to 84.4%. Similarly, the hospitalists exhibited a rise from 69.4% to 74.3%, and the others demonstrated an increase from 79.3% to 83.7%. All observed changes yielded a p-value < 0.001. Conclusions By deploying a multifaceted strategy that emphasized physician education, patient education, EMR initiatives, accountability measures, and daily mobility, there was a statistically significant increase in the rate of patient discharges to home. These initiatives proved to be cost-effective and led to a tangible reduction in healthcare-associated costs and patient length of stay. Further studies are required to look into the effect on hospital readmission rates and morbidity and mortality rates. The comprehensive approach showcased its potential to optimize patient outcomes.

Pylephlebitis-induced acute liver failure: A case report and review of literature.

BACKGROUND: Pylephlebitis is an extremely rare form of septic thrombophlebitis involving the portal vein, carrying high rates of morbidity and mortality. CASE SUMMARY: We present a case of a 42-year-old male with no past medical history who presented with acute onset of abdominal pain and altered mental status with laboratory tests demonstrating new-onset acute liver failure. Pylephlebitis was determined to be the underlying etiology due to subsequent workup revealing polymicrobial gram-negative anaerobic bacteremia and complete thrombosis of the main and left portal veins. To our knowledge, this is the first documented case of acute liver failure as a potential life-threatening complication of pylephlebitis. CONCLUSION: Our case highlights the importance of considering pylephlebitis in the broad differential for abdominal pain, especially if there are co-existing risk factors for hypercoagulability. We also demonstrate that fulminant hepatic failure in these patients can potentially be reversible with the immediate initiation of antibiotics and anticoagulation.

Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the FAERS Database.

BACKGROUND: Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo. OBJECTIVE: Our study's aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19. METHOD: We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with "Covid-19" excluded. RESULTS: A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively. CONCLUSIONS AND RELEVANCE: This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.

Improving Discharge Rates to Home With the Help of Mobility Technicians: A Step in the Right Direction.

Background Early ambulation during acute hospitalization has been associated with improved clinical outcomes for patients. Despite the benefits of mobility in the hospital setting, physical therapists and nursing staff are often constrained by time. Mobility technicians (MTs) are individuals with specialized training who have emerged as a potential solution by providing safe ambulation for patients during their hospital stay. Objectives The purpose of this quality improvement project was to investigate the impact of MTs on clinical and financial outcomes for admitted patients at a high-volume tertiary institution. Methods A quality improvement project was implemented at Jersey Shore University Medical Center, Neptune City, from October 2022 to March 2023. The study was a prospective, single-institution cohort study and included patients admitted to two medical floors. Patients were divided into an experimental group that received services from MTs and a control group that did not receive this service but was eligible based on clinical status. The primary endpoint was the proportion of patients discharged to home. Secondary outcomes included the length of stay and financial impact. Results A total of 396 admitted patients were included, with 222 patients in the MT group and 174 in the non-MT group. Patients in the MT group were discharged home more frequently, at a rate of 79.7% compared to 66.1% for patients in the non-MT group (p = 0.002). MTs contributed to an average 2.4-day reduction in the length of hospital stay (7.8 days vs. 10.2 days, p = 0.007). The MT intervention led to an estimated net savings of $148,500 during the six-month study period. Additionally, 2.9 daily hospital beds were created. Conclusion Implementing an MT program significantly increased the discharge-to-home rates and decreased hospital length of stay. Preliminary analysis suggests that this intervention is cost-effective and can assist institutions in managing increased hospital capacity strain through the creation of additional hospital beds.

Impact of consolidation chemotherapy in poor responders to neoadjuvant radiation therapy: magnetic resonance imaging-based clinical-radiological correlation in high-risk rectal cancers.

PURPOSE: The current study was conducted to examine the role of consolidation chemotherapy after neoadjuvant radiation therapy (NART) in decreasing the involvement of the mesorectal fascia (MRF) in high-risk locally advanced rectal cancers (LARCs). METHODS: In total, 46 patients who received consolidation chemotherapy after NART due to persistent MRF involvement were identified from a database. A team of 2 radiologists, blinded to the clinical data, studied sequential magnetic resonance imaging (MRI) scans to assess the tumor response and then predict a surgical plan. This prediction was then correlated with the actual procedure conducted as well as histopathological details to assess the impact of consolidation chemotherapy. RESULTS: The comparison of MRI-based parameters of sequential images showed significant downstaging of T2 signal intensity, tumor height, MRF involvement, diffusion restriction, and N category between sequential MRIs (P < 0.05). However, clinically relevant downstaging (standardized mean difference, > 0.3) was observed for only T2 signal intensity and diffusion restriction on diffusion-weighted imaging. No clinically relevant changes occurred in the remaining parameters; thus, no change was noted in the extent of surgery predicted by MRI. Weak agreement (Cohen κ coefficient, 0.375) and correlation (Spearman rank coefficient, 0.231) were found between MRI-predicted surgery and the actual procedure performed. The comparison of MRI-based and pathological tumor response grading also showed a poor correlation. CONCLUSION: Evidence is lacking regarding the use of consolidation chemotherapy in reducing MRF involvement in LARCs. The benefit of additional chemotherapy after NART in decreasing the extent of planned surgery by reducing margin involvement requires prospective research.

The Utilization of 15-Minute Multidisciplinary Rounds to Reduce Length of Stay in Patients under Observation Status.

With the recent change to value-based care, institutions have struggled with the appropriate management of patients under observation. Observation status can have a huge impact on hospital and patient expenses. Institutions have implemented specialized observation units to provide better care for these patients. Starting in January 2020, coinciding with the initiation of daily multidisciplinary rounds, our study focused on patients aged 18 and older admitted to our hospital under observation status. Efforts were built upon prior initiatives at Jersey Shore University Medical Center (JSUMC) to optimize patient care and length of stay (LOS) reduction. The central intervention revolved around the establishment of daily "Observation Huddles"-succinct rounds led by hospital leaders to harmonize care for patients under observation. The primary aim was to assess the impact of daily multidisciplinary rounds (MDR) on LOS, while our secondary aim involved identifying specific barriers and interventions that contributed to the observed reduction. Our study revealed a 9-h reduction in observation time, resulting in approximately USD 187.50 saved per patient. When accounting for the period spanning 2020 to 2022, potential savings totaled USD 828,187.50 in 2020, USD 1,046,062.50 in 2021, and USD 1,243,562.50 in 2022. MDR for observation patients led to a reduction in LOS from 29 h to 20 h (p < 0.001).

Lessons learnt from 1300 consecutive gallbladder cancer surgeries: Evolving role of peri-operative chemotherapy in the treatment paradigm.

BACKGROUND: Level I evidence for multi-modality management of gallbladder cancers (GBC) is evolving. METHODS: Prospectively maintained operative GBC database of 1307 patients (year 2010-2019) was analysed to study the impact of peri-operative chemotherapy (PCT) on survival outcomes. RESULTS: 1040 patients had pathologically confirmed GBC. Stage distribution showed: Stage I(85,8.2%), II(247,23.8%), III(460,44.2%), IV(248, 23.8%). PCT was used as follows: in stage II, 164 patients received adjuvant chemotherapy(ACT); in stage III, ACT was given to 444 patients, either operated upfront(244 patients) or after neoadjuvant chemotherapy (NACT)(216 patients); in stage IV, 32 patients (11 received NACT) underwent radical surgery followed by ACT and 216 patients had inoperable disease (77 received NACT) upon exploration. With a median follow-up of 30 months, the 3-year OS for stage I, II and III was 94.1%, 82.6% and 48.2% respectively. Corresponding DFS was 93.8%, 67.3% and 38.3%. Upon reassessment for surgery after NACT (n = 332), patients who underwent radical surgery (n = 235) had superior OS (p = 0.000) and DFS (p = 0.000) in comparison to those who had inoperable disease (n = 97). Amongst stage III and IV patients with operable disease (n = 492), those who were operated upfront (n = 238) had equivalent survival as those operated after NACT (n = 254). This was also confirmed by a 1:1 propensity matched analysis (118 patients each), matching for T and N stage. CONCLUSION: The role of peri-operative chemotherapy in management of GBC is evolving. While the role of NACT for locally advanced GBC is unsettled and merits testing prospectively, it helps in selection of patients with favourable disease biology for radical surgery.

Rare Presentation of Stercoral Ulcer Spontaneous Perforation Without Preceding Radiographic Evidence of Colonic Inflammation and Fecal Impaction.

Stercoral ulcers are caused by persistent fecal impaction. A life-threatening consequence of stercoral ulcers is colonic perforation, which is rare. A high index of clinical suspicion should be held for patients with stercoral ulcer, as colonic perforation is a medical emergency, requiring immediate surgical intervention. Here, we report a case of a 45-year-old female admitted with sepsis of unknown picture and subsequently developed stercoral ulcer perforation (SUP), diagnosed intraoperatively, without prior radiographic evidence of colonic inflammation. She was successfully managed with emergency laparotomy and left colectomy with sigmoid colectomy.

Radical surgery for stage IV gallbladder cancers: Treatment strategies in patients with limited metastatic burden.

Backgrounds/Aims: The present study looked at the role of radical surgery in gallbladder cancers (GBC) with limited metastatic disease. Methods: The retrospective observational study was conducted to screen the database from 1st January 2010 to 31st December 2019. Patients of GBC found to have low-volume metastatic disease upon surgical exploration were included. Results: Of the 1,040 patients operated for GBC, 234 patients had low-volume metastatic disease (microscopic disease in station 16b1 node or N2 disease isolated port-site metastases, or low burden peritoneal disease with deposits less than 1 cm, in adjacent omentum or adjacent diaphragm or Morrison's pouch or a solitary discontinuous liver metastasis in adjacent liver parenchyma) detected intraoperative. Of these, 62 patients underwent radical surgery for R-0 metastatic disease followed by systemic therapy, while the remaining 172 patients did not undergo radical surgery and were given palliative systemic chemotherapy. Patients who underwent radical surgery had significantly superior overall survival (19 months versus 12 months, p < 0.01) and superior progression-free survival (10 months versus 5 months, p < 0.01) when compared to the rest. This difference in survival was more significant amongst patients when operated on after neoadjuvant chemotherapy. Regression analysis showed that a sub-group of patients with incidental GBC with limited metastases showed more favorable outcomes with radical surgery. Conclusions: Authors suggest a possible role for radical treatment of advanced GBC with a limited metastatic burden. Neoadjuvant chemotherapy can be used for preferentially selecting patients of favorable disease biology for curative treatment.

Rate of Multidrug-resistance to Antimicrobial Drugs in Patients in Pediatric Neurointensive Care.

Background: Multidrug-resistant (MDR) organisms in the critical care unit are a worldwide concern. The vulnerability to MDR infection in pediatric patients admitted in neurocritical care are due to altered mental status, immature immune system, higher risk of aspiration, and more frequent use of invasive devices. We aimed to measure the burden of MDR infection in pediatric neurosurgical intensive care unit (NSICU) patients. Methods: All pediatric patients between 1 and 18 years for intracranial and spine surgeries admitted for more than 48 hours in NSICU were enrolled in the study. If patients showed a clinical picture of pneumonia, bloodstream infection (BSI), or urinary tract infection (UTI) after receiving mechanical ventilation or an indwelling device for at least 48 hours, samples of tracheal aspirates, urine, blood, and cerebrospinal fluid (CSF) were sent for microbiological culture. We noted the type of organism, MDR infection rate, and associated risk factors. Pearson Chi-squared test and Fisher's test were used for statistical analysis; p < 0.05 was considered statistically significant. Results: A total of 274 pediatric patients were studied. In 1 year, there was a total of 1,790 patient days. The inclusive MDR infection rate was 17.3/1,000 patient days. Also, Klebsiella pneumoniae (38.7%) was the commonest MDR pathogen. The commonest source of infection was BSI (32.3%). The risk factors associated with MDR infections were the length of stay in NSICU, mechanical ventilation of more than 5 days, emergency surgery, respiratory and cardiac comorbidities, and poor nutrition status (p < 0.05). Conclusion: The MDR infection rate in our study was 17.3/1,000 patient days in pediatric patients. Also, K. pneumonia e was found to be the commonest MDR pathogen. Bloodstream was the commonest source of infection. How to cite this article: Patel S, Prabhakar H, Kapoor I. Rate of Multidrug-resistance to Antimicrobial Drugs in Patients in Pediatric Neurointensive Care. Indian J Crit Care Med 2023;27(1):67-72.

Free Functional Platysma Transfer for Restoration of Spontaneous Eye Closure in Facial Paralysis.

BACKGROUND: Facial palsy patients experience an array of problems ranging from functional to psychological issues. With regard to the eye, lacrimation, lagophthalmos, and the inability to spontaneously blink are the main symptoms and, if left untreated, can compromise the cornea and vision. This article reports the outcomes of 23 free functional vascularized platysma transfers used for reanimation of the eye in unilateral facial paralysis. METHODS: Data were collected prospectively for all patients undergoing reanimation of the paralyzed eye using free functional platysma transfer. The only exclusion criterion was that a minimum of a 2-year follow-up was required. Patients were assessed preoperatively and postoperatively and scored using the eFACE tool focusing on eye-symmetry with documentation of blink reflex. RESULTS: A total of 26 free functional platysma transfers were completed between 2011 and 2018; three patients were excluded because of inadequate follow-up. The mean age was 9.1 ± 7.1 years and there were 12 boys and 11 girls. Preoperatively, no patients had evidence of a blink reflex in comparison to 22 patients at 2-year follow-up. There was a statistically significant improvement in palpebral fissure ( P < 0.001) and full eye closure ( P < 0.001) scores at 2-year follow-up; however, there was no statistically significant difference in gentle eye closure ( P = 0.15). CONCLUSIONS: This is the first report of free functional platysma long-term outcomes in eye reanimation. The results demonstrate that successful restoration of the blink reflex can be achieved and full eye closure is obtainable following surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Functional Results After Nerve-Sparing, Sphincter Preserving Rectal Cancer Surgery: Patient-Reported Outcomes of Sexual and Urinary Dysfunction.

There is an ongoing unmet need of early identification and discussion regarding the sexual and urinary dysfunction in the peri-operative period to improve the quality of life (QoL), particularly in young rectal cancer survivors. Retrospective analysis of prospectively maintained database was done. Male patients less than 60 years who underwent nerve preserving, sphincter sparing rectal cancer surgery between January 2013 and December 2019, were screened. International Index of Erectile Function (IIEF-5) questionnaire was given to assess erectile dysfunction (ED). Patients were asked questions regarding their sexual and urinary function from the EORTC-QL CRC 38 questionnaire, and responses were recorded. Patients were also asked to report any retrograde ejaculation in post-operative period. Sixty-two patients were included in the study. Fifty-four patients (87.1%) received a diversion stoma. Sixteen patients (29.6%) felt stoma was interfering with their sexual function. Six patients (9.7%) reported retrograde ejaculation. Only 5 patients (8.06%) had moderate to severe ED, and the rest had none to mild ED. On univariate and multivariate analysis, only age predicted the development of clinically significant ED. Ten patients (16.1%) had significantly reduced sexual urges, and 23 patients (37.1%) had significant decrease in sexual satisfaction after surgery. Five patients (8.06%) reported having minor urinary complaints. No patient reported having major complaint pertaining to urinary health. While long-term urinary complaints are infrequent, almost half the patient suffered from erectile dysfunction in some form. There is a weak but significant association of age and ED. Follow-up clinic visits provide an ideal opportunity to counsel patients and provide any medical intervention, when necessary.

A Rare and Unusual Cause of Ischemic Stroke to Be Aware of.

Congenital absence of an internal carotid artery (ICA) is an extremely rare vascular anomaly. This case report presents an instance of right ICA agenesis to highlight the importance of early identification of this anomaly and its impact on disease presentation and complications. With transient ischemic attack (TIA), cerebrovascular accident (CVA), and cerebral aneurysms being among the chief presenting scenarios or course of the anomaly, it is important to have a high level of suspicion for these in patients with known ICA agenesis. Understanding the underlying development of this vasculature and its impact on cerebral circulation aids in identifying possible findings on imaging. This case report aims to delineate the pathophysiology of ICA agenesis, recognition of the vasculature that contributes to the anomaly, different presentations of the disease, complications, and obstacles in management.

Type 5 Cardiorenal Syndrome: An Underdiagnosed and Underrecognized Disease Process of the American Mother.

Cardiorenal syndrome (CRS) continues to be an area of concern due to the changing understanding of identification, pathophysiology and optimal management. Originally thought that diuretics were always the answer, recent literature has shed lights on the five major CRS subphenotypes, and while conceptual in their classifications, different strategies may be utilized to manage each type. The effect of CRS in pregnant women is largely under discussed and underappreciated as its own entity. Trials involving possible management, specifically utilizing serelaxin, a recombinant form of relaxin, have shown promising results but more data are needed to begin implementing it on a large scale.