Variations in colorectal cancer surgery practice across the United Kingdom during the COVID-19 pandemic - 'Every land has its own law'.

BACKGROUND: In March 2020 NHS England issued guidelines recognizing the elective component of cancer surgeries may be 'curtailed', due to staffing and supply shortages during the COVID-19 pandemic. However, it suggested, 'local solutions' should be sought in order to protect the delivery of cancer services. We aimed to compare surgeons' practice for the provision of colorectal (CR) cancer surgery across the United Kingdom (UK), against updated Joint Royal Colleges & ACPGBI guidelines and highlight differences in practice, if any. METHOD: An online survey was conducted. It examined surgical practice across the UK against current protocols for CR cancer surgeries, during the COVID-19 pandemic. RESULTS: 29 individual responses were received from 23 NHS Trusts across the UK. 23/29 (79%) surgeons ceased or experienced delays in their CR cancer surgeries during the pandemic, with 3/29 (10%) yet to reintroduce these services. 19/26 (73%) surgeons instructed their patients to self-isolate prior to surgery, of which 5/19 (26%) correctly enforced a duration of 14 days. 10/19 (53%) participants adhered to guidelines of performing a CT chest within 24 h of surgery. 10/26 (38%) participants believe their patients are experiencing longer hospital admissions in the COVID-19 setting. CONCLUSION: This snap shot survey highlights the dramatic variations in CR cancer surgery practice within the UK and inconsistent adherence to protocols. Guidelines will no doubt change as our knowledge of COVID-19 increases both nationally and internationally. It is essential CR surgeons keep up to date with changes in guidance, so uniformity in practice can be maintained.

A New Zealand White rabbit model of thrombocytopenia and coagulopathy following total body irradiation across the dose range to induce the hematopoietic-subsyndrome of acute radiation syndrome.

PURPOSE: The purpose if this study was to develop a rabbit model of total body irradiation (TBI) -induced thrombocytopenia and coagulopathy across the dose-range which induces the hematopoietic subsyndrome of the acute radiation syndrome (H-ARS). METHODS: Twenty male New Zealand White rabbits were assigned to arms to receive 6-MV of TBI at a dose of 6.5, 7.5, 8.5 or 9.5 Gy. Animals were treated with moderate levels of supportive care including buprenorphine for pain management, antibiotics, antipyretics for rectal body temperature >104.8 °F, and fluids for signs of dehydration. Animals were closelyfollowed for up to 45 days after TBI for signs of major morbidity/mortality. Hematology and serum chemistry parameters were routinely monitored. Hemostasis parameters were analyzed prior to TBI, 2 and 6 hours post-TBI, and at the time of euthanasia. RESULTS: Animals developed the characteristic signs and symptoms of H-ARS during the first-week post TBI. Animals became thrombocytopenic with signs of severe acute anemia during the second week post TBI. Moribund animals presented with petechia and ecchymosis of the skin and generalized internal hemorrhage. Multiorgan dysfunction characterized by bone marrow failure, gastric ileus, acute renal toxicity, and liver abnormalities were common. Severe abnormalities in coagulation parameters were observed. CONCLUSIONS: The presentation of bone marrow failure and multiorogan injury associated with ARS in the New Zealand White rabbit model is consistent with that described in the canine, swine, non-human primate, and in humans. The hemorrhagic syndrome associated with the ARS in rabbits is characterized by thrombocytopenia and hemostasis dysfunction, which appear to underlie the development of multiorgan dysfunction following TBI to rabbits. Taken together, the rabbit recapitulates the pathogenesis of ARS in humans, and may present an alternative small animal model for medical countermeasure pilot efficacy screening, dose-finding and schedule optimization studies prior to moving into large animal models of TBI-induced ARS.

Characterization of the hemorrhagic syndrome in the New Zealand white rabbit model following total body irradiation.

PURPOSE: The hemorrhagic syndrome is a major cause of morbidity and mortality associated with the acute radiation syndrome (ARS). We previously characterized the dose-response relationship for total body irradiation (TBI)-induced ARS in the New Zealand White (NZW) rabbit. Thrombocytopenia, hemorrhage, and anemia were strongly associated with morbidity/mortality during the first three weeks post-TBI. The objective of the current study was to further characterize the natural history of thrombocytopenia, hemostatic dysfunction and hemorrhage in the rabbit model at a TBI dose range to induce ARS. METHODS: Fifty male NZW rabbits were randomized to receive 7.0 or 7.5 Gy of 6 MV-derived TBI. Sham-irradiated controls (n = 6) were included as a comparator. Animals were treated with minimal supportive care including pain medication, antibiotics, antipyretics for temperature >104.8 °F, and fluids for signs of dehydration. Animals were culled at pre-determined timepoints post-TBI, or for signs of imminent mortality based on pre-defined euthanasia criteria. Hematology parameters, serum chemistry, viscoelasticity of whole blood, coagulation tests, and coagulation factor activities were measured. A gross exam of vital organs was performed at necropsy. RESULTS: Findings in this study include severe neutropenia during the first week post-TBI followed by thrombocytopenia and severe acute anemia with petechial hemorrhages of the skin and hemorrhage of the vital organs during the second to third weeks post-TBI. Abnormalities in whole blood viscoelastometry were observed concurrent with thrombocytopenia and hemorrhage. Antithrombin activity was significantly elevated in animals after exposure to 7.5 Gy, but not 7.0 Gy TBI. CONCLUSIONS: The hemorrhagic syndrome in the rabbit model of TBI recapitulates the pathogenesis described in humans following accidental or deliberate exposures. The rabbit may present an alternative to the rodent model as a small animal species for characterization of the full spectrum of multiorgan injury following TBI and early testing of promising medical countermeasures.

Knowledge and practice towards care and maintenance of peripheral intravenous cannula among nurses in Chitwan Medical College Teaching Hospital, Nepal.

AIM: The study is mainly concerned about the care and maintenance of peripheral intravenous cannulation: to determine the knowledge and practice of nurses towards care and maintenance of IV cannula and to find out the obstacles encountered in caring and maintaining IV cannula. Intravenous cannulation is a common procedure performed by nurses in every hospital and closely associated with the risk of nosocomial infections if standard care is not provided. DESIGN: A descriptive cross-sectional study design was carried out. METHODS: Nurses' knowledge and practice towards care and maintenance of peripheral intravenous cannula were assessed using a validated semi-structured self-administered questionnaire through the census method. Data were analysed through SPSS program. The comparison was done between knowledge and practice. RESULTS: The findings revealed that 84.72% respondents were doing correct practices despite the fact that only 82.47% respondents had proper knowledge. Most nurses have good knowledge of caring and maintaining peripheral intravenous cannulation but there were some without proper knowledge and practice. This could be a potential risk factor for patient safety.

BIO 300, a nanosuspension of genistein, mitigates pneumonitis/fibrosis following high-dose radiation exposure in the C57L/J murine model.

BACKGROUND AND PURPOSE: BIO 300 nanosuspension (Humanetics Corporation) is being developed as a medical countermeasure (MCM) for the mitigation of the delayed effects of acute radiation exposure, specifically pneumonitis and fibrosis of the lung. The objective of this study was to determine the best dose and treatment duration of BIO 300 to mitigate lung injury and improve the likelihood for survival in C57L/J mice exposed to whole thorax lung irradiation (WTLI). EXPERIMENTAL APPROACH: Age- and sex-matched C57L/J mice received a single dose of 11.0 or 12.5 Gy WTLI. BIO 300 (200 or 400 mg·kg-1 , oral gavage) was administered daily starting 24 h post-exposure for a duration of 2, 4, 6 or, in some cases, 10 weeks. Non-treated controls were included for comparison in both sexes. Animals were observed daily for signs of major morbidity. Respiratory function was assessed biweekly. Lungs were collected, weighed and paraffin embedded for histological evaluation post mortem. KEY RESULTS: BIO 300 administered at an oral dose of 400 mg·kg-1 for 4 to 6 weeks starting 24 h post-WTLI reduced morbidity associated with WTLI. The improvement in survival correlated with reduced respiratory frequency and enhanced pause. The irradiated lungs of mice treated with BIO 300 (400 mg·kg-1 ) for 4 to 6 weeks displayed less morphological damage and airway loss due to oedema, congestion and fibrotic scarring than the untreated, irradiated controls. CONCLUSIONS AND IMPLICATIONS: BIO 300 is a promising MCM candidate to mitigate pneumonitis/fibrosis when administered daily for 4-6 weeks starting 24 h post-exposure.

Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease.

Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 h post-exposure demonstrated >5000 genes to be differentially expressed (P<0.01; >twofold change) between strains with early versus late onset of disease. An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis, DNA replication and cell division. At 24 h post-WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains but microscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with the macroscopic expression of injury manifesting weeks to months after exposure. Understanding the mechanisms underlying development of RILD might lead to more rational selection of therapeutic interventions to mitigate healthy tissue damage.

Community acquired multi-drug resistant clinical isolates of Escherichia coli in a tertiary care center of Nepal.

BACKGROUND: Multi-drug resistance (MDR) in Gram-negative organisms is an alarming problem in the world. MDR and extensively-drug resistance (XDR) is in increasing trend due to the production of different types of beta (ß)-lactamases. Thus the aim of this study was to document the incidence of MDR and XDR in clinical isolates of Escherichia coli and also to find out the enzymatic mechanisms of ß-lactam antibiotics resistance. METHODS: Two hundred clinical isolates of Escherichia coli (E. coli) identified by standard laboratory methods were studied. Antibiotic susceptibility profile was performed for all the isolates and the suspected isolates were phenotypically tested for the production of extended spectrum ß-lactamase (ESBL), metallo ß-lactamase (MBL) and AmpC ß-lactamase (AmpC) by recommended methods. RESULTS: Around three-fourth (78%) of the total isolates were multi-drug resistant. ESBL, MBL and AmpC production was found in 24%, 15% and 9% of isolates respectively. Amikacin, chloramphenicol and colistin were found to be the most effective antibiotics. CONCLUSIONS: High percentage of MDR was observed. ß-lactamase mediated resistance was also high. Thus, regular surveillance of drug resistance due to ß-lactamases production and infection control policy are of utmost importance to minimize the spread of resistant strains.