Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial.

BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care. METHODS: Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion. RESULTS: Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation. CONCLUSION: Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.

Multiple umbilical cord strictures in a case of intrauterine foetal demise.

INTRODUCTION: Umbilical cord abnormalities include short cord, long cord, knots, hyper-coiling, hypo-coiling, stricture, single umbilical artery, supernumerary umbilical vessels, cystic and vascular malformation, and abnormal insertion of cord like velamentous and furcate insertions. We report a case of intrauterine death in a fetus with multiple umbilical cord strictures and vascular thrombosis. CASE REPORT: A 35-year-old woman delivered a stillborn female fetus at 33 weeks of gestation. No fetal anomaly was detected. Examination of the umbilical cord showed multiple strictures, located 4.5 cm and 20 cm from the placental insertion site. Microscopically, the stricture site showed Wharton's jelly being replaced by fibrosis with presence of vascular thrombosis. DISCUSSION: Umbilical cord stricture is uncommon and has been described to be associated with intrauterine fetal death and a possibility of recurrent. There is a need to counsel the parents and close fetal surveillance in subsequent pregnancy is advise since the risk of recurrent remains uncertain.

Synchronous polypectomy during endoscopic diagnosis of colorectal cancer - is the risk of tumour implantation at the polypectomy site significant?

BACKGROUND: Synchronous polypectomy in colonic malignancies is contentious due to the perceived risks of tumour implantation at polypectomy sites (PS). We assess the risks of tumour implantation after synchronous polypectomy. METHODS: An analysis of all endoscopies for cancer that were accompanied by synchronous polypectomies from 2005 to 2009 was performed. The incidence of metachronous colorectal cancers located at the same segment of a previous PS was the surrogate for tumour implantation. Data on patient demographics, tumour and polyp location(s) and follow-up outcomes were extracted. The rate of metachronous lesions at the same segment of a previous PS between patients who had all synchronous PS resected (Group A) and patients with PS left in-situ (Group B) were compared. RESULTS: Two hundred and eighty-four patients had synchronous polypectomy performed during their initial endoscopy for cancer. Three patients were lost to follow-up and, in the remaining 281 patients, 87 (31.0%) were in Group A while 194 (69%) were in Group B. Median age, gender, tumour location, tumour stage, and pathological characteristics were similar between both groups. 2 (0.7%) patients developed local recurrences. Six (2.1%) patients developed metachronous lesions, four of which were located at the same segment where synchronous polypectomy was previously performed. The rates of metachronous lesions at the PS in groups A and B were similar at 1.1% (1/87) and 1.5% (3/194), respectively (p = 0.795). CONCLUSION: Malignant implantation after synchronous polypectomy in the setting of a newly diagnosed cancer remains unproven. Even if tumor implantation did occur, the incidence is likely low.

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis.

BACKGROUND: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. METHODS: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. RESULTS: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32-0.77); P<0.01], but no difference in complication rates [OR 1.02 (0.88-1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62-0.92); P<0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61-0.88); P<0.01; I2=89%). CONCLUSIONS: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

Validation of the Swedish version of Quality of Recovery score -15: a multicentre, cohort study.

BACKGROUND: Quality of recovery (QoR) after surgery is often focused on morbidity, mortality and physiological changes, while well-being and emotional state are other important aspects that are often ignored. QoR is poorly investigated in clinical settings and a psychometrically tested questionnaire, QoR-15, has recently been developed. QoR-15 has not been validated for Swedish conditions. The aim of this study was to translate, adapt and validate QoR-15 to Swedish conditions (QoR-15swe). METHODS: A translation and cultural adaption was performed resulting in a Swedish version of the instrument, QoR-15swe. Patients answered the QoR-15swe before surgery, 24 and 48 h after surgery. Feasibility, validity, reliability and responsiveness of the QoR-15swe were evaluated. RESULTS: The QoR-15swe was feasible in 85.5% of the eligible patients. Construct validity was good, with significant correlations between QoR-15swe score and, ASA-PS class, grade of surgery, length of surgery and time in the post-anaesthesia care unit. The instrument demonstrated good internal consistency with an inter-item Cronbach's α of 0.83-0.87, and inter-dimension Cronbach's α was acceptable 0.71-0.76. Test-retest repeatability was also good with Cronbach's alpha > 0.99 and an interclass correlation coefficient of 0.992 (CI: 0.981-0.997). There were no floor and ceiling effects. Responsiveness assessed by Cliff's effect size was -0.23 indicating a moderate ability to detect change at 24 h postoperatively. CONCLUSION: We have translated and culturally adapted the QoR-15 into Swedish. The score demonstrated acceptable validity, reliability and responsiveness. The QoR-15swe is a clinically acceptable and feasible outcome measure after surgery in a Swedish population.

Diagnostic conundrum of a perineal tumour: a rectal gastrointestinal stromal tumour mimic.

Gastrointestinal stromal tumour (GIST) is a common mesenchymal tumour arising in the gastrointestinal tract, but not frequently encountered in the rectum. Herein, we describe a case of a rectal GIST which mimicked histomorphological features of a schwannoma; thus, making intraoperative frozen section evaluation challenging. Although subsequent immunohistochemistry and molecular findings readily confirmed the diagnosis of a GIST, we wish to draw attention to three clues that will help the pathologist steer clear of this potential diagnostic pitfall. One, GISTs are relatively more common than schwannomas in the rectum. Two, schwannomas usually have very little mitoses. Three, rectal GISTs commonly exhibit nuclear palisades. We also discuss the diagnostic, prognostic and therapeutic functions of immunohistochemical and molecular investigations. As the surgical intent for rectal GISTs is for en-bloc excision with wide margins, we surmise that the intraoperative consult should include GIST as a possible differential diagnosis for rectal mesenchymal tumours. In view of the potential for neoadjuvant treatment with imatinib before surgical excision to preserve sphincter function, a multidisciplinary approach is recommended for establishing most effective treatment strategy in these rare complex cases.

Cyclooxygenase-2 (COX2) expression in adenocarcinoma surpasses that of squamous cell carcinoma in the uterine cervix.

Over the years, adenocarcinoma (ADC), which has a worse prognosis than squamous cell carcinoma (SCC) of the cervix, has shown an increasing trend. Cyclooxygenase-2 (COX2) expression which has been associated with worse prognosis in several solid cancers was studied for its association with SCC and ADC of the cervix. 35 histologically re-confirmed SCC and 35 ADC were immunohistochemically stained for COX2 using a mouse monoclonal antibody to COX2 (1:100; Dako: Clone CX-294) on a Ventana Benchmark XT. The histoscore was computed as intensity of staining, semi-quantitated on a scale of 0-3 with 0 = negative, 1 = weak, 2 = moderate and 3 = strong staining intensity; multiplied by percentage of immunopositivity on a scale of 0-4 with 0 = <1%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75% and 4 = ≥75% of immunopositive tumour cells. Histoscore 1-3/12 was considered as low and ≥4/12 as high COX2 expression. SCC affected Chinese more than Malays, while Malays had more ADC (p = 0.032). Mean age at presentation of SCC (57.5 years) was about a decade later than ADC at 47.9 years (p = 0.002). 30/35 (85.7%) of SCC and 34/35 (97.1%) of ADC expressed COX2. Histoscores of ADC (median = 4.0, IQR = 3.0-6.0) was significantly higher (p = 0.014) than those of SCC (median = 3.0, IQR = 2.0-3.0). High histoscores (≥4/12) were more frequent in ADC (55.9%) compared with SCC (26.7%) (p = 0.018), implicating COX2, either directly or indirectly, as a possible player in influencing the poorer outcome of ADC compared with SCC.

A scoring model for predicting survival following primary tumour resection in stage IV colorectal cancer patients with unresectable metastasis.

BACKGROUND: Stage IV colorectal cancer patients with unresectable metastasis who undergo elective primary tumour resection experience heterogeneous post-operative survival. We aimed to develop a scoring model for predicting post-operative survival using pre-operative variables to identify patients who are least likely to experience extended survival following the procedure. METHODS: Survival data were collected from stage IV colorectal cancer patients who had undergone elective primary tumour resection between January 1999 and December 2007. Coefficients of significant covariates from the multivariate Cox regression model were used to compute individual survival scores to classify patients into three prognostic groups. A survival function was derived for each group via Kaplan-Meier estimation. Internal validation was performed. RESULTS: Advanced age (hazard ratio, HR 1.43 (1.16-1.78)); poorly differentiated tumour (HR 2.72 (1.49-5.04)); metastasis to liver (HR 1.76 (1.33-2.33)), lung (HR 1.37 (1.10-1.71)) and bone (HR 2.08 ((1.16-3.71)); carcinomatosis (HR 1.68 (1.30-2.16)); hypoalbuminaemia (HR 1.30 (1.04-1.61) and elevated carcinoembryonic antigen levels (HR 1.89 (1.49-2.39)) significantly shorten post-operative survival. The scoring model separated patients into three prognostic groups with distinct median survival lengths of 4.8, 12.4 and 18.6 months (p < 0.0001). Internal validation revealed a concordance probability estimate of 0.65 and a time-dependent area under receiver operating curve of 0.75 at 6 months. Temporal split-sample validation implied good local generalizability to future patient populations (p < 0.0001). CONCLUSION: Predicting survival following elective primary tumour resection using pre-operative variables has been demonstrated with the scoring model developed. Model-based survival prognostication can support clinical decisions on elective primary tumour resection eligibility.

Preoperative abnormalities in serum sodium concentrations are associated with higher in-hospital mortality in patients undergoing major surgery.

BACKGROUND: Abnormal serum sodium concentrations are common in patients presenting for surgery. It remains unclear whether these abnormalities are independent risk factors for postoperative mortality. METHODS: This is a secondary analysis of the European Surgical Outcome Study (EuSOS) that provided data describing 46 539 patients undergoing inpatient non-cardiac surgery. Patients were included in this study if they had a recorded value of preoperative serum sodium within the 28 days immediately before surgery. Data describing preoperative risk factors and serum sodium concentrations were analysed to investigate the relationship with in-hospital mortality using univariate and multivariate logistic regression techniques. RESULTS: Of 35 816 (77.0%) patients from the EuSOS database, 21 943 (61.3%) had normal values of serum sodium (138-142 mmol litre(-1)) before surgery, 8538 (23.8%) had hyponatraemia (serum sodium ≤137 mmol litre(-1)) and 5335 (14.9%) had hypernatraemia (serum sodium ≥143 mmol litre(-1)). After adjustment for potential confounding factors, moderate to severe hypernatraemia (serum sodium concentration ≥150 mmol litre(-1)) was independently associated with mortality [odds ratio 3.4 (95% confidence interval 2.0-6.0), P<0.0001]. Hyponatraemia was not associated with mortality. CONCLUSIONS: Preoperative abnormalities in serum sodium concentrations are common, and hypernatraemia is associated with increased mortality after surgery. Abnormalities of serum sodium concentration may be an important biomarker of perioperative risk resulting from co-morbid disease.

Palliative surgical intervention in metastatic colorectal carcinoma: a prospective analysis of quality of life.

AIM: Quality of life (QOL) was assessed after palliative surgery for incurable metastatic colorectal cancer (CRC). METHOD: Newly diagnosed patients with incurable metastatic CRC who were offered elective palliative surgical intervention were included. The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaire was used for the assessment of QOL at baseline and at 3 and 6 months after surgery. Generalized estimating equations were used to estimate the mean change in the QOL score from baseline. RESULTS: Twenty-four patients formed the study group. Sixteen underwent resection of the primary tumour and eight had a proximal diversion or bypass. The Global Health (GH) score and Social Functioning (SF) score improved at 3 and 6 months after intervention respectively (GH +11, P = 0.021; SF +15, P = 0.005). Mean anxiety scores were markedly improved from the baseline of 51 to 71 (P = 0.004, 3 months) and 76 (P = 0.002, 6 months). Weight concerns also improved significantly when compared with baseline (3 months, +20, P < 0.001; 6 months, +14, P = 0.012). Symptoms of diarrhoea (3 months, --17, P = 0.007; 6 months,--16, P = 0.008) and nausea (--8, P = 0.032) improved. CONCLUSION: In patients with incurable metastatic CRC, surgery improved QOL.

Shock treatment in a cohort of Scandinavian intensive care units in 2014.

BACKGROUND: Shock is common in intensive care units, and treatment includes fluids, vasopressor and/or inotropic drugs, guided by hemodynamic monitoring. The aim of this study was to identify current practice for treatment of shock in Scandinavian intensive care units. METHODS: Seven-day inception cohort study in 43 intensive care units in Scandinavia. Patients ≥ 15 years old receiving more than 4 h of cardiovascular acting drug infusion were included. The use of fluids, vasopressor and inotropic drugs, type of monitoring, and target values were recorded. RESULTS: One hundred and seventy-one patients were included. At inclusion, 136/168 (81%) had received vasopressor and/or inotropic drug therapy for less than 24 h, and 143/171 (84%) had received volume loading before the onset of vasoactive drug treatment. Ringer's solution was given to 129/143 (90%) of patients and starches in 3/143 (2%) patients. Noradrenaline was the most commonly used cardiovascular acting drug, given in 168/171 (98%) of cases while dopamine was rarely used. Mean arterial pressure was considered the most important variable for hemodynamic monitoring. Invasive arterial blood pressure was monitored in 166/171 (97%) of patients, arterial pulse wave analysis in 11/171 (7%), and echocardiography in 50/171 (29%). CONCLUSION: In this survey, Ringer's solution and noradrenaline were the most common first-line treatments in shock. The use of starches and dopamine were rare. Almost all patients were monitored with invasive arterial blood pressure, but comprehensive hemodynamic monitoring was used only in a minority of patients.

Anti-dengue virus serotype 2 activity and mode of action of a novel peptide.

AIM: To identify a novel antiviral peptide against dengue virus serotype 2 (DENV-2) by screening a phage display peptide library and to evaluate its in vitro antiviral activity and mode of action. METHODS AND RESULTS: A phage display peptide library was biopanned against purified DENV-2 and resulted in the identification and selection of a peptide (peptide gg-ww) for further investigation. ELISA was performed, and peptide gg-ww was shown to possess the highest binding affinity against DENV-2. Thus, peptide gg-ww was synthesized for cytotoxicity and antiviral assays. Virus plaque reduction assay, real-time PCR and immunofluorescence assay were used to investigate the inhibitory effect of peptide gg-ww on DENV-2 infection in Vero cells. Three different assays (pre-, simultaneous and post-treatments assays) were performed to investigate the peptide's mode of action. Results indicated that peptide gg-ww possessed strong antiviral activity with a ~96% inhibition rate, which was achieved at 250 µmol l(-1) . Viral replication was inhibited during a simultaneous treatment assay, indicating that the entry of the virus was impeded by this peptide. CONCLUSIONS: Peptide gg-ww displayed antiviral action against DENV-2 by targeting an early stage of viral replication (i.e. during viral entry). SIGNIFICANCE AND IMPACT OF THE STUDY: Peptide gg-ww may represent a new therapeutic candidate for the treatment of DENV infections and is a potential candidate to be developed as a peptide drug.

A comprehensive ovine model of blood transfusion.

BACKGROUND: The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. MATERIALS AND METHODS: Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC. RESULTS: Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline-adenine-glucose-mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. CONCLUSION: These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions.

Stored blood transfusion induces transient pulmonary arterial hypertension without impairing coagulation in an ovine model of nontraumatic haemorrhage.

BACKGROUND AND OBJECTIVES: Transfusion of blood products in particular older products is associated with patient morbidity. Previously, we demonstrated a higher incidence of acute lung injury in lipopolysaccharide-treated sheep transfused with stored blood products. As transfusion following haemorrhage is more common, we aimed to determine whether a 'first hit' of isolated haemorrhage would precipitate similar detrimental effects following transfusion and also disrupt haemostasis. MATERIALS AND METHODS: Anaesthetized sheep had 33% of their total blood volume collected into Leukotrap bags (Pall Medical), which were processed into packed red blood cells and cross-matched for transfusion into other sheep. After 30 mins, the sheep were resuscitated with either: fresh (<5 days old) or stored (35-42 days old) ovine blood followed by 4% albumin to replacement volume, albumin alone or normal saline alone and monitored for 4 h. RESULTS: The first hit of haemorrhage precipitated substantial decreases in mean arterial pressure however haemostasis was preserved. Transfusion of stored ovine blood induced (1) transient pulmonary arterial hypertension but no oedema and (2) reduced fibrinogen levels more than fresh blood, but neither induced coagulopathy. Thus, transfusion of stored blood affected pulmonary function even in the absence of overt organ injury. CONCLUSION: The fact that stored blood transfusions: (1) did not induce acute lung injury in contrast to previous lipopolysaccharide-primed animal models identifies the 'first hit' as an important determinant of the severity of transfusion-mediated injury; (2) impaired pulmonary dynamics verifies the sensitivity and vulnerability of the pulmonary system to injury.

Ischemic colitis due to a dissecting aneurysm of the superior rectal artery.

Ischemic injury to the bowel is a disease entity that has a wide spectrum of pathological and clinical findings. Patients with chronic ischemia present with colicky abdominal pain, obstructive symptoms and signs of ischemic colonic stricture. We reported the first case of ischemic colitis arising from a superior rectal artery (SRA) aneurysm. Colonoscopy showed non-resolving colitis complicated by sigmoid stricture. CT angiogram with 3D reconstruction showed a dissecting SRA aneurysm measuring 2 cm by 1.2 cm by 1.3 cm. The patient underwent laparoscopic-assisted low anterior resection, which was converted to open because of adhesions and made a full recovery.

Young colorectal carcinoma patients do not have a poorer prognosis: a comparative review of 2,426 cases.

BACKGROUND: Colorectal cancer (CRC) in "young" patients under 50 years of age is uncommon. There have been conflicting reports regarding both the clinicopathological features of CRC in young patients and prognosis. The aim of this study was to review and compare the clinical characteristics, prognostic factors, and overall survival of patients in three different age groups (40 years and under, 41-50 years, over 50 years of age) and the prognosis of these patients. METHODS: A total of 2,426 consecutive patients who had undergone surgical resection for sporadic colorectal cancer at Singapore General Hospital in the period from 2000 to 2005 were retrieved from a prospectively collected computer database. There were 73 patients (3.0 %) in Group 1 (40 years old or less), 257 (10.6 %) in Group 2 (41-50 years old), and 2,096 (86.4 %) in Group 3 (>50 years old). Clinicopathological features were assessed using univariate analysis to evaluate significant differences, survival curves were constructed using the Kaplan-Meier method, and multivariate analysis was performed to evaluate the independent prognostic factors. RESULTS: Young CRC patients tend to present with a higher incidence of mucinous and signet ring cell tumors (Group 1-20.5 %, Group 2-8.2 %, Group 3-6.2 %, p < 0.001) and have more poorly differentiated tumors (Group 1-20.0 %, Group 2-9.7 %, Group 3-7.4 %, p = 0.014). Furthermore, young CRC patients tend to present with regional lymph node metastases (Group 1-65.7 %, Group 2-60.8 %, Group 3-51.0 %, p = 0.001) and distant metastases (Group 1-31.5 %, Group 2-24.1 %, Group 3-19.4 %, p = 0.006). Multivariate analysis reveals, however, that young age is not an independent prognostic factor for cancer-specific survival (CSS) (p = 0.392). Five-year CSS for Group 1 was 56.6 % (95 % confidence interval (CI) 44.8-68.4 %), Group 2 53.8 % (95 % CI 47.3-60.3 %), and Group 3 61.1 % (95 % CI 58.9-63.3 %). CONCLUSIONS: Although presenting with advanced tumors and with poorer prognostic factors such as presence of mucin and poor histological differentiation, young CRC patients do not have a worse prognosis.