Developing a hyperthermic intraperitoneal chemotherapy (HIPEC) gynecologic oncology program: a Canadian experience.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for epithelial ovarian cancer following cytoreductive surgery. The intraperitoneal spread of the disease makes the peritoneal cavity an ideal target for drug delivery. HIPEC has shown promising results in improving overall survival in epithelial ovarian cancer patients when performed during interval cytoreductive surgery. Recent studies have provided level 1 evidence supporting increased overall survival in stage III ovarian cancer patients treated with HIPEC during interval cytoreduction. Meta-analyses have further confirmed the survival improvement in women receiving HIPEC. Despite its inclusion in guidelines, many centers have been hesitant to implement HIPEC programs due to perceived obstacles, such as increased morbidity, cost, and resource requirements. Studies have shown that morbidity rates are acceptable in selected patients, and the addition of HIPEC to cytoreductive surgery is cost effective. Therefore, the main barrier to implementing HIPEC programs is related to resource requirements and logistics, but with proper preparation, these challenges can be overcome. Establishing a successful HIPEC program requires institutional support, a knowledgeable and dedicated team, adequate resources and equipment, and proper training and audit. This review aims to provide evidence based information to guide the development of successful HIPEC programs, including preoperative, anesthetic, and surgical considerations. It also reviews the different equipment and protocols for the perfusion and common postoperative events.

Gastric-type adenocarcinoma of the endocervix: Potentially overcoming resistant behavior with surgery.

Objective: Gastric-type adenocarcinoma of the endocervix (GAS) is a rare form of human papillomavirus-independent cervical cancer commonly described as an insidious disease bearing a poor prognosis. Based on scarce data, uncertainty persists pertaining to its oncologic management. Method: All cases of well-differentiated GAS treated at our institution from 2010 to 2021 were reviewed. Clinical characteristics, diagnostic tests results and oncologic outcomes were recorded and analyzed. Kaplan-Meier curves and log rank test were performed to compare survival curves between patients with tumors confined to the cervix (group 1: up to stage IB3) versus locally advanced or metastatic (group 2: stages II to IV). Results: Cervical cytologies and biopsies yielded low detection rates (38 and 42% respectively) leading to 87% of patients with locally advanced or metastatic disease at diagnosis. Median overall survival (OS) was 40.0 ± 15.9 months with a clear dichotomy in survival when comparing patients with disease confined to the cervix to those with higher stages (respectively 59.0 vs 12.0 months, p = 0.047). None of the 5 patients initially managed with concurrent chemoradiotherapy (CCRT) responded to treatment but fortunately 3 of the latter achieved remission after surgery. Conclusion: Well-differentiated GAS did not show favorable response to chemotherapy and radiation. Surgical resection seems to be a cornerstone in the management of this disease, as all patients who achieved remission were treated with surgery, either upfront or after suboptimal response to CCRT. We suggest considering aggressive upfront surgery when feasible. If CCRT is selected to avoid upfront exenterative procedures, rapid evaluation of tumor response is recommended.

Hyperthermic Intraperitoneal Chemotherapy and Interval Debulking Surgery in Conjunction With Elective Cesarean Delivery.

BACKGROUND: Ovarian cancer is rare during pregnancy. For patients beyond 20 weeks of gestation who choose to continue the pregnancy, neoadjuvant chemotherapy may be initiated, followed by interval debulking surgery. Hyperthermic intraperitoneal chemotherapy (HIPEC) may be used with interval debulking surgery for stage III epithelial ovarian cancer, but data are lacking on its administration in the peripartum period. CASE: We illustrate the case of a 40-year-old patient diagnosed with stage III epithelial ovarian cancer at 27 weeks of gestation who underwent neoadjuvant chemotherapy followed by cesarean delivery at term along with interval debulking surgery and HIPEC. The intervention was well tolerated and resulted in the birth of a healthy neonate. The postoperative period was unremarkable, and the patient is disease-free after 22-months of follow-up. CONCLUSION: We demonstrate the feasibility of peripartum HIPEC. Optimal oncologic care should not be jeopardized by the peripartum state of an otherwise healthy patient.

Recommendations for Canada's National Action Plan to End Gender-Based Violence: perspectives from leaders, service providers and survivors in Canada's largest city during the COVID-19 pandemic. / Recommandations pour le Plan d'action national pour mettre fin à la violence fondée sur le genre : points de vue de dirigeants, de fournisseurs de services et de survivantes dans la plus grande ville du Canada pendant la pandémie de COVID-19.

INTRODUCTION: The Canadian government has committed to a national action plan (NAP) to address violence against women (VAW). However, a formalized plan for implementation has not been published. Building on existing recommendations and consultations, we conducted the first formal and peer-reviewed qualitative analysis of the perspectives of leaders, service providers and survivors on what should be considered in Canada's NAP on VAW. METHODS: We applied thematic analysis to qualitative data from 18 staff working on VAW services (11 direct support, 7 in leadership roles) and 10 VAW survivor participants of a community-based study on VAW programming during the COVID-19 pandemic in the Greater Toronto Area (Ontario, Canada). RESULTS: We generated 12 recommendations for Canada's NAP on VAW, which we organized into four thematic areas: (1) invest into VAW services and crisis supports (e.g. strengthen referral mechanisms to VAW programming); (2) enhance structural supports (e.g. invest in the full housing continuum for VAW survivors); (3) develop coordinated systems (e.g. strengthen collaboration between health and VAW systems); and (4) implement and evaluate primary prevention strategies (e.g. conduct a gender-based and intersectional analysis of existing social and public policies). CONCLUSION: In this study, we developed, prioritized and nuanced recommendations for Canada's proposed NAP on VAW based on a rigorous analysis of the perspectives of VAW survivors and staff in Canada's largest city during the COVID-19 pandemic. An effective NAP will require investment in direct support organizations; equitable housing and other structural supports; strategic coordination of health, justice and social care systems; and primary prevention strategies, including gender transformative policy reform.

Performance of a Semiquantitative Multiplex Bacterial and Viral PCR Panel Compared With Standard Microbiological Laboratory Results: 396 Patients Studied With the BioFire Pneumonia Panel.

BACKGROUND: Microbiologic results are critical to optimal management of patients with lower respiratory tract infection, but standard methods may take several days. The multiplex polymerase chain reaction BioFire Pneumonia (PN) panel detects 15 common bacterial species semiquantitatively as copy number/mL, 8 viral species, and 7 resistance genes in about an hour within the clinical laboratory. METHODS: We tested 396 unique endotracheal or bronchoalveolar lavage specimens with the BioFire Pneumonia panel and compared the bacterial detections to conventional gram stain and culture results. RESULTS: Of the 396 patients, 138 grew at least 1 bacterium that had a target on the PN panel, and 136/138 (98.6%) were detected by the panel. A total of 177 isolates were recovered in culture and the PN panel detected 174/177 (98.3%). A further 20% of patients had additional targets detected that were not found on standard culture (specificity 69%, positive predictive value 63%, and negative predictive value 98.9%). Copy number was strongly related to standard semiquantitative growth on plates reported by the laboratory (eg, 1+, 2+, 3+ growths) and was significantly higher in those specimens that grew a potential pathogen. Both higher copy number and bacterial detections found by the PN panel, but not found in culture, were strongly positively related to the level of white blood cells reported in the initial gram stain. CONCLUSIONS: Higher copy number and bacterial detections by the PN panel are related to the host respiratory tract inflammatory response. If laboratories can achieve a rapid turnaround time, the PN panel should have a significant impact both on patient management and on antibiotic stewardship.

Implementation of an external female urinary catheter as an alternative to an indwelling urinary catheter.

BACKGROUND: Until recently, there has been a lack of viable alternative to an indwelling urinary catheter for female patients that require precise urine output measurements. With the introduction of external female urinary catheters, we can now substitute this type of device for an indwelling urinary catheter in many patients, decreasing their risk of catheter-associated urinary tract infections. METHODS: In this retrospective study, we analyzed the impact of a hospital-wide implementation of an external female urinary catheter at a large academic medical center. The study included female patients, greater than 18 years of age. We compared a 12-month period before and after device implementation to assess the impact on indwelling urinary catheter utilization and catheter-associated urinary tract infections rate. RESULTS: Data included over 220,000 patient days, over 10,000 external urinary catheter days and 33,000 indwelling urinary catheter days. We found a statistically significant decrease in indwelling urinary catheter utilization following the implementation of the external female urinary catheter, but only in intensive care units. CONCLUSIONS: It is our recommendation that facilities first implement the device in ICUs as this level of care was where we observed the most significant impact.

Hyperthermic intraoperative thoracoabdominal chemotherapy for stage IVB epithelial ovarian carcinoma.

•Full-thickness diaphragmatic infiltration with pleural effusion in advanced epithelial ovarian cancer is challenging.•Short-term control of malignant pleural effusion with HITAC for advanced epithelial ovarian cancer seems feasible.•Carboplatin is safe when used as HIPEC or HITAC agent for advanced epithelial ovarian cancer.

Educational Case: Identification of Pulmonary Mycobacteria.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Evaluation of patient risk factors for infection with carbapenem-resistant Enterobacteriaceae.

BACKGROUND: To evaluate risk factors for infection or colonization with carbapenem-resistant Enterobacteriaceae (CRE) to develop an algorithm for targeted CRE screening. METHODS: We conducted a case-control study of 50 CRE-positive cases and 100 CRE-negative controls to identify risk factors that were significant for CRE infection or colonization. The setting was at an acute care academic hospital. Patients who tested positive for CRE or other microbiological laboratory tests during the study period were included. We reviewed medical records of 50 patients who were CRE-positive and 100 matched controls who had a non-CRE culture at a similar anatomic site within the closest time period to the case's culture date. Risk factors were assessed using logistic regression with SAS 9.4, observing the 95% confidence interval (CI) to determine significance. RESULTS: Significant risk factors for CRE infection or colonization included the use of fluoroquinolones (odds ratio [OR], 3.75; 95% CI, 1.35, 10.38) and cephalosporins (OR, 2.37; 95% CI, 1.17, 4.86). In addition, undergoing an invasive procedure with a scope device was also a significant risk factor for our participants (OR, 4.57; 95% CI, 1.31, 16.02). Significance of these risk factors varied within the community-acquired and hospital-acquired cases. CONCLUSIONS: Our results suggest that exposure to certain antimicrobials and invasive procedures with a scope device (endoscopic retrograde cholangiopancreatography, duodenal endoscope) are risk factors for CRE. The findings of significant differences in antimicrobials received highlight the necessity to understand antimicrobial stewardship in the development of CRE colonization and infection. Along with antibiotics, inaccessibility to components within scope devices may be increasing the risk of CRE spread.

Evaluating differences in tuberculosis and nontuberculous mycobacterial lung disease in Florida.

BACKGROUND: Currently, very little data exists that compare the features of pulmonary nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis (TB). Both have similar symptomology and analogous preliminary laboratory results, as both present with positive acid-fast bacilli stains. The objective of this study was to provide data that would help guide clinicians in their decision making regarding isolation precautions for patients, with a preliminary positive result for mycobacteria, prior to species identification. METHODS: We conducted queries for patients who had positive respiratory cultures for mycobacteria via our electronic medical record system, between January 1, 2011, and December 31, 2017. Additionally, we collected demographic and medical history, clinical presentation, and radiographic findings. The 2-sample unpaired Student t test, the Χ2 test, and logistic regression were used to compare each group. RESULTS: Through logistic regression, 8 variables were significantly associated with patients who grew either TB or NTM. History of incarceration, born outside of the United States, cavitation, and lymphadenopathy were associated with TB; tobacco smoke exposure, pre-existing lung disease, immunosuppression, and bronchiectasis were associated with NTM. Incidence of HIV and hemoptysis was not significantly different between the 2 groups. CONCLUSIONS: Through the use of our study findings, improper use of airborne isolation precautions may be reduced or avoided.

Assessment of current methicillin-resistant Staphylococcus aureus screening protocols and outcomes at an academic medical center.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for many hospital-associated infections. Both MRSA-colonized and MRSA-infected patients must be isolated on contact precautions per the Centers for Disease Control and Prevention guidelines. This study evaluates the current practice for removing MRSA-colonized patients from contact precautions and proposes a new protocol to decrease inconsistencies with screening methodologies. METHODS: This was a retrospective chart review of MRSA screening swabs collected at an academic medical center between January 1, 2010 and December 31, 2017. Of those patients with MRSA screening swabs, extra-nasal cultures were also evaluated for MRSA infection. Screening swabs were analyzed for appropriateness of order and timing between swabs and active infections. Analysis of variance and the χ² tests were used to determine significance between groups. RESULTS: This study included 8,310 patients with a combined total of 11,601 nasal swabs. Significantly more (P = .0159) patients with 2 negative nasal swabs returned with a recurrent MRSA infection or colonization than those who had 3 consecutive negative nasal swabs (27.8% vs 17.0%, respectively). Additionally, 47.8% of patients only had 1 appropriately ordered negative nasal swab, indicating that a nurse-driven protocol may be more effective in obtaining the full series of samples required to remove contact precautions. CONCLUSIONS: The current practice for removing a patient from contact precautions for MRSA is insufficient. The number of negative nasal swabs required should be increased from 2 to 3 and a decolonization protocol should be implemented.

A Gastrointestinal PCR Panel Improves Clinical Management and Lowers Health Care Costs.

Conventional methods for the identification of gastrointestinal pathogens are time-consuming and expensive and have limited sensitivity. The aim of this study was to determine the clinical impact of a comprehensive molecular test, the BioFire FilmArray gastrointestinal (GI) panel, which tests for many of the most common agents of infectious diarrhea in approximately 1 h. Patients with stool cultures submitted were tested on the GI panel (n = 241) and were compared with control patients (n = 594) from the year prior. The most common organisms detected by the GI panel were enteropathogenic Escherichia coli (EPEC, n = 21), norovirus (n = 21), rotavirus (n = 15), sapovirus (n = 9), and Salmonella (n = 8). Patients tested on the GI panel had an average of 0.58 other infectious stool tests compared with 3.02 in the control group (P = 0.0001). The numbers of days on antibiotic(s) per patient were 1.73 in the cases and 2.12 in the controls (P = 0.06). Patients with the GI panel had 0.18 abdomen and/or pelvic imaging studies per patient compared with 0.39 (P = 0.0002) in the controls. The average length of time from stool culture collection to discharge was 3.4 days in the GI panel group versus 3.9 days in the controls (P = 0.04). The overall health care cost could have decreased by $293.61 per patient tested. The GI panel improved patient care by rapidly identifying a broad range of pathogens which may not have otherwise been detected, reducing the need for other diagnostic tests, reducing unnecessary use of antibiotics, and leading to a reduction in hospital length of stay.

Removing Cerebrospinal Fluid Antibody Orders from the Test Menu Results in a Dramatic Decrease in Order Volume.

BACKGROUND: Antibody tests for Borrelia burgdorferi (agent of Lyme disease), Toxoplasma gondii, and cytomegalovirus in cerebrospinal fluid (CSF) are rarely useful. One reason for misutilization of laboratory tests is simply the convenience offered by a computerized physician order entry (CPOE) system. METHODS: The cytomegalovirus (CMV) antibodies-CSF, B. burgdorferi antibodies-CSF, and T. gondii antibodies-CSF orders were removed from the test menu. A provider could still order these tests using a miscellaneous order. We collected monthly volumes of test orders before and after the tests were removed from the CPOE. RESULTS: Orders for CSF antibody testing for B. burgdorferi, T. gondii, and CMV decreased by 91%, 93%, and 98%, respectively (P < 0.01), after they were removed from the CPOE test menu. This result correlates to a savings of $50053.44 per year. Additionally, we did not see a paradoxical increase in CMV PCR or T. gondii PCR orders after the intervention. CONCLUSIONS: Removal of test orders from the CPOE dramatically decreased test order volume, which led to substantial cost savings and availability of CSF for more useful tests. There was no compensatory increase in order volume for related tests, indicating that providers were not looking for alternate tests.

Multiplex gastrointestinal pathogen panels: implications for infection control.

In the acute care hospital inpatient setting, there is a wide variety of causes for both infectious and noninfectious diarrhea. However, without molecular assays for the wide range of agents causing gastroenteritis, there is no reliable way to determine which individuals should be placed in contact precautions, as recommended by CDC. We tested 158 inpatient diarrheal stool specimens with the FilmArray GI Panel (BioFire Diagnostics, Salt Lake City, UT, USA) that had been stored at -70°C after testing negative by conventional methods for Clostridium difficile and/or rotavirus. We found that 22.2% had at least 1 other infectious agent detected, and 60% of these patients were never placed in appropriate isolation for a total of 109 patient-days. In addition, 20.3% of patients with negative GI panel results could have been removed from isolation. Use of multiplex gastrointestinal panels may improve decisions regarding patient isolation and reduce nosocomial transmission.

Loss-of-function de novo mutations play an important role in severe human neural tube defects.

BACKGROUND: Neural tube defects (NTDs) are very common and severe birth defects that are caused by failure of neural tube closure and that have a complex aetiology. Anencephaly and spina bifida are severe NTDs that affect reproductive fitness and suggest a role for de novo mutations (DNMs) in their aetiology. METHODS: We used whole-exome sequencing in 43 sporadic cases affected with myelomeningocele or anencephaly and their unaffected parents to identify DNMs in their exomes. RESULTS: We identified 42 coding DNMs in 25 cases, of which 6 were loss of function (LoF) showing a higher rate of LoF DNM in our cohort compared with control cohorts. Notably, we identified two protein-truncating DNMs in two independent cases in SHROOM3, previously associated with NTDs only in animal models. We have demonstrated a significant enrichment of LoF DNMs in this gene in NTDs compared with the gene specific DNM rate and to the DNM rate estimated from control cohorts. We also identified one nonsense DNM in PAX3 and two potentially causative missense DNMs in GRHL3 and PTPRS. CONCLUSIONS: Our study demonstrates an important role of LoF DNMs in the development of NTDs and strongly implicates SHROOM3 in its aetiology.