Preclinical 3D model screening reveals digoxin as an effective therapy for a rare and aggressive type of endometrial cancer.

OBJECTIVE: Dedifferentiated endometrial carcinoma (DDEC) characterized by SWItch/Sucrose Non-Fermentable (SWI/SNF) complex inactivation is a highly aggressive type of endometrial cancer without effective systemic therapy options. Its uncommon nature and aggressive disease trajectory pose significant challenges for therapeutic progress. To address this obstacle, we focused on developing preclinical models tailored to this tumor type and established patient tumor-derived three-dimensional (3D) spheroid models of DDEC. METHODS: High-throughput drug repurposing screens were performed on in vitro 3D spheroid models of DDEC cell lines (SMARCA4-inactivated DDEC-1 and ARID1A/ARID1B co-inactivated DDEC-2). The dose-response relationships of the identified candidate drugs were evaluated in vitro, followed by in vivo evaluation using xenograft models of DDEC-1 and DDEC-2. RESULTS: Drug screen in 3D models identified multiple cardiac glycosides including digoxin and digitoxin as candidate drugs in both DDEC-1 and DDEC-2. Subsequent in vitro dose-response analyses confirmed the inhibitory activity of digoxin and digitoxin with both drugs showing lower IC50 in DDEC cells compared to non-DDEC endometrial cancer cells. In in vivo xenograft models, digoxin significantly suppressed the growth of DDEC tumors at clinically relevant serum concentrations. CONCLUSION: Using biologically precise preclinical models of DDEC derived from patient tumor samples, our study identified digoxin as an effective drug in suppressing DDEC tumor growth. These findings provide compelling preclinical evidence for the use of digoxin as systemic therapy for SWI/SNF-inactivated DDEC, which may also be applicable to other SWI/SNF-inactivated tumor types.

Assessing Educational and Attitudinal Outcomes of a Student Learner Experience Focused on Homelessness.

BACKGROUND AND OBJECTIVES: Patient navigation programs help guide vulnerable populations, such as those experiencing homelessness, through the health care system. Medical students developed the student-run Patient Navigator Program (PNP) to serve persons experiencing homelessness (PEH) in the Dallas area. The objective of this study was to build on previously published data to determine how medical student attitudes, knowledge, and confidence working with PEH changed during involvement in the PNP, particularly after participating as a patient navigator. METHODS: Student fellows completed a survey prior to a training elective (time point 1), immediately after the training elective (time point 2), and after acting as a patient navigator (time point 3). The PNP survey, which intended to measure student attitudes and knowledge regarding PEH, included the Health Professionals' Attitudes Toward the Homeless Inventory (HPATHI) and the Student-Run Free Clinic Project (SRFCP) surveys. In our analysis, we compared responses among the different time points. RESULTS: Seventy-six of 88 students who completed the training elective chose to participate in the PNP fellowship. Skills, knowledge, and self-efficacy improved from time points 1 to 2, 1 to 3, and 2 to 3. Social advocacy also improved from time points 1 to 2 and 1 to 3. CONCLUSIONS: Improvements from time point 1 to 2 demonstrated the value of didactic learning, while further improvements from time point 2 to 3 demonstrated the added benefit of hands-on experiential learning. Our study illustrates the potential educational benefits that a PNP provides to medical students who may encounter or care for this population during their careers.

High-throughput deconvolution of 3D organoid dynamics at cellular resolution for cancer pharmacology with Cellos.

Three-dimensional (3D) organoid cultures are flexible systems to interrogate cellular growth, morphology, multicellular spatial architecture, and cellular interactions in response to treatment. However, computational methods for analysis of 3D organoids with sufficiently high-throughput and cellular resolution are needed. Here we report Cellos, an accurate, high-throughput pipeline for 3D organoid segmentation using classical algorithms and nuclear segmentation using a trained Stardist-3D convolutional neural network. To evaluate Cellos, we analyze ~100,000 organoids with ~2.35 million cells from multiple treatment experiments. Cellos segments dye-stained or fluorescently-labeled nuclei and accurately distinguishes distinct labeled cell populations within organoids. Cellos can recapitulate traditional luminescence-based drug response of cells with complex drug sensitivities, while also quantifying changes in organoid and nuclear morphologies caused by treatment as well as cell-cell spatial relationships that reflect ecological affinity. Cellos provides powerful tools to perform high-throughput analysis for pharmacological testing and biological investigation of organoids based on 3D imaging.

Establishment and validation of preclinical models of SMARCA4-inactivated and ARID1A/ARID1B co-inactivated dedifferentiated endometrial carcinoma.

OBJECTIVE: Dedifferentiated endometrial cancer (DDEC) is an uncommon and clinically highly aggressive subtype of endometrial cancer characterized by genomic inactivation of SWItch/Sucrose Non-Fermentable (SWI/SNF) complex protein. It responds poorly to conventional systemic treatment and its rapidly progressive clinical course limits the therapeutic windows to trial additional lines of therapies. This underscores a pressing need for biologically accurate preclinical tumor models to accelerate therapeutic development. METHODS: DDEC tumor from surgical samples were implanted into immunocompromised mice for patient-derived xenograft (PDX) and cell line development. The histologic, immunophenotypic, genetic and epigenetic features of the patient tumors and the established PDX models were characterized. The SMARCA4-deficienct DDEC model was evaluated for its sensitivity toward a KDM6A/B inhibitor (GSK-J4) that was previously reported to be effective therapy for other SMARCA4-deficient cancer types. RESULTS: All three DDEC models exhibited rapid growth in vitro and in vivo, with two PDX models showing spontaneous development of metastases in vivo. The PDX tumors maintained the same undifferentiated histology and immunophenotype, and exhibited identical genomic and methylation profiles as seen in the respective parental tumors, including a mismatch repair (MMR)-deficient DDEC with genomic inactivation of SMARCA4, and two MMR-deficient DDECs with genomic inactivation of both ARID1A and ARID1B. Although the SMARCA4-deficient cell line showed low micromolecular sensitivity to GSK-J4, no significant tumor growth inhibition was observed in the corresponding PDX model. CONCLUSIONS: These established patient tumor-derived models accurately depict DDEC and represent valuable preclinical tools to gain therapeutic insights into this aggressive tumor type.

Cellos: High-throughput deconvolution of 3D organoid dynamics at cellular resolution for cancer pharmacology.

Three-dimensional (3D) culture models, such as organoids, are flexible systems to interrogate cellular growth and morphology, multicellular spatial architecture, and cell interactions in response to drug treatment. However, new computational methods to segment and analyze 3D models at cellular resolution with sufficiently high throughput are needed to realize these possibilities. Here we report Cellos (Cell and Organoid Segmentation), an accurate, high throughput image analysis pipeline for 3D organoid and nuclear segmentation analysis. Cellos segments organoids in 3D using classical algorithms and segments nuclei using a Stardist-3D convolutional neural network which we trained on a manually annotated dataset of 3,862 cells from 36 organoids confocally imaged at 5 µm z-resolution. To evaluate the capabilities of Cellos we then analyzed 74,450 organoids with 1.65 million cells, from multiple experiments on triple negative breast cancer organoids containing clonal mixtures with complex cisplatin sensitivities. Cellos was able to accurately distinguish ratios of distinct fluorescently labelled cell populations in organoids, with ≤3% deviation from the seeding ratios in each well and was effective for both fluorescently labelled nuclei and independent DAPI stained datasets. Cellos was able to recapitulate traditional luminescence-based drug response quantifications by analyzing 3D images, including parallel analysis of multiple cancer clones in the same well. Moreover, Cellos was able to identify organoid and nuclear morphology feature changes associated with treatment. Finally, Cellos enables 3D analysis of cell spatial relationships, which we used to detect ecological affinity between cancer cells beyond what arises from local cell division or organoid composition. Cellos provides powerful tools to perform high throughput analysis for pharmacological testing and biological investigation of organoids based on 3D imaging.

Use of the McGRATH™ MAC videolaryngoscope to evaluate the ability of anesthetists to give effective cricoid pressure: An interventional study.

Background and Aims: The application of cricoid pressure (CP) for rapid sequence induction is questioned on two grounds: its effectiveness in clinical settings and its impact on the laryngeal view. The main reason cited for its ineffectiveness is the lack of knowledge and training in its correct application. This study assessed, the performance of anesthetists in applying effective CP in a clinical setting. Material and Methods: Eighty-five ASA I/II adult patients posted for elective surgery requiring oral endotracheal intubation with nasogastric tube (NGT) placement participated in the study. Eighty-five anesthetists divided into five groups based on their level of experience were randomly chosen to apply CP after induction of anesthesia. An experienced anesthetist performed videolaryngoscopy and attempted NGT insertion. The primary outcome was effectiveness of CP defined as the inability to pass the NGT into the esophageal opening. We also noted that the glottic view with and without CP and the effectiveness of CP across different levels of experience of anesthetists. Results: Of the 85 anesthetists, 61 (71.8%) applied effective CP. The effectiveness improved with experience (first-year residents-11/17 [64.7%], second-year residents-11/17 [64.7%], third-year residents-10/17 [58.8%], senior residents-13/17 [76.5%], and consultants-16/17 [94.1%]) (P = 0.157). Post hoc analysis showed higher effectiveness among anesthetists with >3 years of experience (85.3%) compared with <3 years of experience (62.7%) (P = 0.024). CP did not always impede the laryngeal view, rather it has no effect or actually improves the glottic view in many instances (81%). Conclusion: CP is effective in occluding the esophageal lumen without hampering glottic view in the majority of the cases, and its effectiveness improves with experience.

Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas.

Triple-negative breast cancer (TNBC) and ovarian carcinomas (OvCas) with BRCA1 promoter methylation (BRCA1meth) respond more poorly to alkylating agents compared to those bearing mutations in BRCA1 and BRCA2 (BRCAmut). This is a conundrum given the biologically equivalent homologous recombination deficiency (HRD) induced by these genetic and epigenetic BRCA perturbations. We dissected this problem through detailed genomic analyses of TNBC and OvCa cohorts and experimentation with patient-derived xenografts and genetically engineered cell lines. We found that despite identical downstream genomic mutational signatures associated with BRCA1meth and BRCAmut states, BRCA1meth uniformly associates with poor outcomes. Exposure of BRCA1meth TNBCs to platinum chemotherapy, either as clinical treatment of a patient or as experimental in vivo exposure of preclinical patient derived xenografts, resulted in allelic loss of BRCA1 methylation and increased BRCA1 expression and platinum resistance. These data suggest that, unlike BRCAmut cancers, where BRCA loss is a genetically "fixed" deficiency state, BRCA1meth cancers are highly adaptive to genotoxin exposure and, through reversal of promoter methylation, recover BRCA1 expression and become resistant to therapy. We further found a specific augmented immune transcriptional signal associated with enhanced response to platinum chemotherapy but only in patients with BRCA-proficient cancers. We showed how integrating both this cancer immune signature and the presence of BRCA mutations results in more accurate predictions of patient response when compared to either HRD status or BRCA status alone. This underscores the importance of defining BRCA heterogeneity in optimizing the predictive precision of assigning response probabilities in TNBC and OvCa.

Impact of an Embedded Palliative Care Clinic on Healthcare Utilization for Patients With a New Thoracic Malignancy.

Introduction: Palliative care is beneficial for patients with advanced lung cancer, but the optimal model of palliative care delivery is unknown. We investigated healthcare utilization before and after embedding a palliative care physician within a thoracic medical oncology "onco-pall" clinic. Methods: This is a retrospective cross-sectional cohort study comparing healthcare outcomes in two cohorts: "pre-cohort" 12 months prior to and "post-cohort" 12-months after the onco-pall clinic start date. Patients were included if they had a new diagnosis of lung cancer and received care at The Ohio State University Thoracic Oncology Center, and resided in Franklin County or 6 adjacent counties. During the pre-cohort time period, access to palliative care was available at a stand-alone palliative care clinic. Palliative care intervention in both cohorts included symptom assessment and management, advance care planning, and goals of care discussion as appropriate. Outcomes evaluated included rates of emergency department (ED) visits, hospital admissions, 30-day readmissions, and intensive care unit (ICU) admissions. Estimates were calculated in rates per-person-years and with Poisson regression models. Results: In total, 474 patients met criteria for analysis (214 patients included in the pre-cohort and 260 patients in the post-cohort). Among all patients, 52% were male and 48% were female with a median age of 65 years (range 31-92). Most patients had non-small cell lung cancer (NSCLC - 17% stage 1-2, 20% stage 3, 47% stage 4) and 16% had small cell lung cancer. The post-cohort was older [median age 66 years vs 63 years in the pre-cohort (p-value: < 0.01)]. The post-cohort had a 26% reduction in ED visits compared to the pre-cohort, controlling for age, race, marital status, sex, county, Charlson score at baseline, cancer type and stage (adjusted relative risk: aRR: 0.74, 95% CI: 0.58-0.94, p-value = 0.01). Although not statistically significant, there was a 29% decrease in ICU admissions (aRR: 0.71, 95% CI: 0.41-1.21, p-value = 0.21) and a 15% decrease in hospital admissions (aRR: 0.85, 95% CI: 0.70-1.03, p-value = 0.10). There was no difference in 30-day readmissions (aRR: 1.03, 95% CI: 0.73-1.45, p-value = 0.85). Conclusions: Embedding palliative care clinics within medical oncology clinics may decrease healthcare utilization for patients with thoracic malignancies. Further evaluation of this model is warranted.

Substance Abuse Risk and Medication Monitoring in Patients with Advanced Lung Cancer Receiving Palliative Care.

Oncology and Palliative Medicine lack guidance on routine opioid risk screening and compliance monitoring. This study explored relationships among risk screening and aberrant medication related behaviors in patients with advanced lung cancer receiving embedded palliative care. This was a single center, prospective study and data was collected from December 2018 to March 2020. At the initial palliative visit, patients provided a baseline urine drug screen (UDS) test and completed the Screener and Opioid Assessment for Patients with Pain - Revised (SOAPP-R) self-assessment. Clinical pharmacists provided comprehensive review and interpretation of UDS results. Among 39 patients, 12 (30.8%) scored positive for risk of aberrant medication behaviors on the SOAPP-R. Only 34 of 39 patients provided a baseline UDS test and were included in further analysis. Prior to pharmacist review, 11/11 (100%) baseline UDS results in the positive-risk group and 13/23 (56.5%) in the negative-risk group appeared unexpected (p = 0.01). After pharmacist review, aberrant baseline UDS results were confirmed for 5/11 (45.5%) positive-risk and 4/23 (17.4%) negative-risk patients (p = 0.11). Overall, the SOAPP-R alone may be inadequate in this population and clinical pharmacists play an important role in comprehensive UDS result interpretation. Future studies are needed to validate this risk-screening tool in palliative cancer populations.

Dietary Glutamic Acid, Obesity, and Depressive Symptoms in Patients With Schizophrenia.

Introduction: Schizophrenia is a lifelong condition associated with several comorbid conditions such as physical illnesses like obesity, as well as co-occurring psychiatric symptoms such as depression. Research regarding susceptibility to some of these comorbidities has primary focused on genetic risks or neurotransmitters and very little work has been done to understand environmental factors such as diet. In particular, understanding the role of dietary glutamic acid consumption on co-morbidities in patients with schizophrenia is important, as evidence suggests that glutamic acid consumption may directly influence glutamatergic neurotransmission; a key neurotransmitter related to schizophrenia, its associated co-morbidities, and depression. Therefore, the aim of this study was to examine the potential relationship between dietary glutamic acid and depressive symptomatology in patients with schizophrenia, stratified by obesity status, due to its relationship with inflammation, antipsychotic use, and depressive symptoms. Methods: Subjects included in this analysis, were part of a parent cross-sectional study in which included three dietary recalls analyzed using protocols outlined as part of the National Health and Nutrition Examination Surveys (NHANES) standardized criteria. Additionally, body mass index (BMI), and Beck Depression Inventory were obtained at this visit. Subjects with a BMI ≥ 30 kg/m2 were included in the obesity group, and the relationship between glutamic acid consumption and BDI scores was analyzed after controlling for age, race, sex, antidepressant and antipsychotic use, and animal and vegetable protein intake which provide natural forms of dietary glutamic acid. Results: A total of 168 participants were included in this study, of which 42.5% were female and 52.9% were White. The mean BMI for the group as a whole was 33.5 ± 8.7 (kg/m2) and the mean BDI was 14.5 ± 10.2 (range 2-50). No differences were found between obesity groups, other than a greater hyperlipidemia, hypertension, and lower waist to hip ratio. Overall, no relationship was found between dietary glutamic acid and BDI scores, However, for non-obese participants, diets higher levels of glutamic acid were associated with greater depression symptomatology (p = 0.021). Conclusion: These preliminary results indicate a possible correlation between dietary glutamic acid a depressive symptoms in non-obese patients with schizophrenia, although further research is needed to specifically examine this relationship.

Prevalence of and Risk Factors for Self-Reported Voice Problems Among Carnatic Singers.

BACKGROUND: Unlike Western opera singing, Carnatic singing requires powerful low pitched, loud voice. Singing in the right Shruti or pitch and appropriate breathing is given the main emphasis in this style of music. The present study was conducted to explore the prevalence of and possible risk factors for the self-reported voice problem (VP) in Carnatic singers. METHOD: This cross-sectional survey was conducted by distributing the self-reporting questionnaires to 190 Carnatic singers in and around the Mysuru and Bengaluru districts of Karnataka state, India, from December 2016 to April 2017. RESULTS: The Carnatic singers were found to have high career (35%) and point (23%) prevalence rates of VP. Clenching of teeth, frequent cold, difficulty in hearing, stress related to the profession, and regular intake of medications for different health-related problems were some of the risk factors found to have a significant association with high prevalence of self-reported VPs. Around 22% of the Carnatic singers missed at least 2-5 singing performances due to VP during their career. CONCLUSIONS: Overall, the results of this study reveal a high prevalence rate of self-reported VP in Carnatic singers, and they also suggest that the VPs are associated with different risk factors like any other form of singers. Further studies are needed to understand the effect of VP and to prevent it in this group of professional voice users.

Mutation S115T in IMP-Type Metallo-ß-Lactamases Compensates for Decreased Expression Levels Caused by Mutation S119G.

(1) Background: Metallo-ß-lactamases (MBLs) have raised concerns due to their ability to inactivate carbapenems and newer generation cephalosporins and the absence of clinically available MBL inhibitors. Their genes are often transferred horizontally, and the number of MBL variants has grown exponentially, with many newer variants showing enhanced enzyme activity or stability. In this study, we investigated a closely related group of variants from the IMP family that all contain the combination of mutations S115T and S119G relative to IMP-1. (2) Methods: The effects of each individual mutation and their combination in the IMP-1 sequence background in comparison to IMP-1 were investigated. Their ability to confer resistance and their in-cell expression levels were determined. All enzymes were purified, and their secondary structure and thermal stability were determined with circular dichroism. Their Zn(II) content and kinetic constants with a panel of ß-lactam antibiotics were determined. (3) Results: All four enzymes were viable and conferred resistance to all antibiotics tested except aztreonam. However, the single-mutant enzymes were slightly deficient, IMP-1S115T due to decreased enzyme activity and IMP-1-S119G due to decreased thermal stability and expression, while the double mutant did not show these defects. (4) Conclusions: These observations suggest that S119G was acquired due to its increased enzyme activity and S115T to suppress the thermal stability and expression defect introduced by S119G.

Preoperative "R wave amplitude variation" on electrocardiogram predicts severe hypovolemia.

Preoperative fasting is essential to prevent aspiration and associated complications. However, quite often patients end up fasting for 12 h or more due to changes in the operating room schedules, delays, and postponements. Preoperative fasting may lead to a fluid deficit, which may contribute to perioperative discomfort and morbidity. We report a case of 44-year-old female posted for total mastectomy with axillary clearance for carcinoma breast, with prolonged fasting where preoperative R wave amplitude variation along with associated changes in the plethysmograph was noticed on the monitor. 500 milliliters of lactated ringer solution was administered before induction of anesthesia, by the time R wave amplitude variation decreased. Variations in plethysmography became normal after 1 L of fluid administration after induction of anesthesia. Gross R wave amplitude variation is not a very common finding and may predict severe hypovolemia in preoperative area in prolonged fasting patients.

The ubiquitin ligase UBE3B, disrupted in intellectual disability and absent speech, regulates metabolic pathways by targeting BCKDK.

Kaufman oculocerebrofacial syndrome (KOS) is a recessive neurodevelopmental disorder characterized by intellectual disability and lack of speech. KOS is caused by inactivating mutations in UBE3B, but the underlying biological mechanisms are completely unknown. We found that loss of Ube3b in mice resulted in growth retardation, decreased grip strength, and loss of vocalization. The brains of Ube3b-/- mice had hypoplasia of the corpus callosum, enlarged ventricles, and decreased thickness of the somatosensory cortex. Ube3b-/- cortical neurons had abnormal dendritic morphology and synapses. We identified 22 UBE3B interactors and found that branched-chain α-ketoacid dehydrogenase kinase (BCKDK) is an in vivo UBE3B substrate. Since BCKDK targets several metabolic pathways, we profiled plasma and cortical metabolomes from Ube3b-/- mice. Nucleotide metabolism and the tricarboxylic acid cycle were among the pathways perturbed. Substrate-induced mitochondrial respiration was reduced in skeletal muscle but not in liver of Ube3b-/- mice. To assess the relevance of these findings to humans, we identified three KOS patients who had compound heterozygous UBE3B mutations. We discovered changes in metabolites from similar pathways in plasma from these patients. Collectively, our results implicate a disease mechanism in KOS, suggest that it is a metabolic encephalomyopathy, and provide an entry to targeted therapies.

A pilot program featuring formative peer review of faculty teaching at a college of pharmacy.

BACKGROUND AND PURPOSE: Although student ratings are the most common method for evaluating faculty performance in the classroom in schools of pharmacy, this should not be the sole approach to provide feedback to faculty regarding teaching. EDUCATIONAL ACTIVITY AND SETTING: This initiative targeted individuals at the ranks of Clinical Assistant or Assistant Professor who taught during the 2016-2017 academic year. As part of the process, the peer reviewer(s) attended a class taught by the faculty member under review. During the observation, the peer reviewer(s) completed rubrics and noted strengths and areas for improvement. Participating faculty members were asked to complete a post-evaluation survey to evaluate the pilot program and offer suggestions for enhancement FINDINGS: Based on a 64.3% response rate (9/14) from reviewers and 92.9% (13/14) from faculty members under review, 100% (9/9) of reviewers and 92.3% (12/13) of faculty members under review would recommend the peer review program to their colleagues. However, 77.8% (7/9) of the reviewers and only 46.2% (6/13) of faculty members under review supported the use of the peer review method as part of the annual faculty evaluation and development process. DISCUSSION/SUMMARY: Ultimately, this process of peer review will be implemented across the college, benefiting faculty evaluation and development, as part of the promotion and tenure process. With our positive feedback and suggestions for improvement, the authors hope this will serve as a guide for institutions to develop peer review programs that will positively supplement student ratings and provide an additional, meaningful form of evaluation for self- improvement and promotion/tenure.

High-resolution deconstruction of evolution induced by chemotherapy treatments in breast cancer xenografts.

The processes by which tumors evolve are essential to the efficacy of treatment, but quantitative understanding of intratumoral dynamics has been limited. Although intratumoral heterogeneity is common, quantification of evolution is difficult from clinical samples because treatment replicates cannot be performed and because matched serial samples are infrequently available. To circumvent these problems we derived and assayed large sets of human triple-negative breast cancer xenografts and cell cultures from two patients, including 86 xenografts from cyclophosphamide, doxorubicin, cisplatin, docetaxel, or vehicle treatment cohorts as well as 45 related cell cultures. We assayed these samples via exome-seq and/or high-resolution droplet digital PCR, allowing us to distinguish complex therapy-induced selection and drift processes among endogenous cancer subclones with cellularity uncertainty <3%. For one patient, we discovered two predominant subclones that were granularly intermixed in all 48 co-derived xenograft samples. These two subclones exhibited differential chemotherapy sensitivity-when xenografts were treated with cisplatin for 3 weeks, the post-treatment volume change was proportional to the post-treatment ratio of subclones on a xenograft-to-xenograft basis. A subsequent cohort in which xenografts were treated with cisplatin, allowed a drug holiday, then treated a second time continued to exhibit this proportionality. In contrast, xenografts from other treatment cohorts, spatially dissected xenograft fragments, and cell cultures evolved in diverse ways but with substantial population bottlenecks. These results show that ecosystems susceptible to successive retreatment can arise spontaneously in breast cancer in spite of a background of irregular subclonal bottlenecks, and our work provides to our knowledge the first quantification of the population genetics of such a system. Intriguingly, in such an ecosystem the ratio of common subclones is predictive of the state of treatment susceptibility, showing how measurements of subclonal heterogeneity could guide treatment for some patients.

Perioperative concerns and management of pressurised intraperitoneal aerosolised chemotherapy: Report of two cases.

Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) is a new, mostly supportive approach to help patients with advanced peritoneal metastasis to increase the lifespan. It carries occupational hazards to health-care workers and especially anaesthesiologist during the procedure. The aerosolised chemotherapy can also cause chemical peritonitis and organ dysfunction in the perioperative period. In this case report, we present the report of two cases and discuss the perioperative concerns and management related to PIPAC.

Hand Hygiene Practices Among Indian Medical Undergraduates: A Questionnaire-Based Survey.

Background and objectives To prevent the spread of infections in all healthcare settings, hand hygiene must be routinely practiced. Appropriate hand hygiene techniques can go a long way in reducing nosocomial infections, cross-transmission of microorganisms and the risk of occupational exposure to infectious diseases. World Health Organisation (WHO) has taken an incredible approach called "My Five Moments for Hand Hygiene" which defines the key moments when health-care workers should perform hand hygiene. We thus carried out a survey to assess knowledge of hand hygiene practices among undergraduate medical students.  Materials and methods A cross-sectional survey was conducted among 523 Indian medical undergraduates. The questionnaire used was adapted from the WHO hand hygiene knowledge questionnaire for health-care workers and was distributed both, in print and online formats. The response to each question was examined using percentages. Results Nearly 57% (n=298) of medical students who participated in this study did not receive any formal training in hand hygiene. Only 27% (n=141) students knew that the most frequent source of germs responsible for health-care associated infections were the germs already present on or within the patient. Nearly 68.6% (n= 359) students were unaware of the sequence of hand washing and hand rubbing. Although 71.9% (n=376 ) students claimed that they use an alcohol-based hand rub routinely, only 36.1% (n=189 ) students knew the time required for a hand rub to kill the germs on the hands. Overall hand hygiene knowledge was low in 6.9% (n=36), moderate in 80.9% (n=423) and good in 12.2% (n=23) of respondents.  Conclusions The awareness about hand hygiene practices among medical students is low. Nearly 57% (n=298) of the respondents never received any formal training in hand hygiene throughout their course of medical undergraduate study. To prevent the spread of infections in healthcare settings, medical students should be given proper training in hand hygiene practices right from the first year of the medical curriculum. This should be done by running workshops and annual seminars on hand hygiene practices and making it a requisite for clinical skills assessment.