A prospective study to evaluate influence of maternal, obstetric and fetal risk factors on the outcome of asphyxiated neonates born intramurally and extramurally

Background: The present study was planned to determine the influence of maternal, obstetric and fetal risk factors on the outcome of intramurally (born at a tertiary care centre) and extramurally (born at a peripheral centre, home or a private facility) born asphyxiated neonates.Methods: It was an observational clinical research with a prospective design and was conducted in Neonatal Intensive Care Unit (NICU), Paediatric Neurology Clinic attached to Department of Paediatrics and Department of Obstetrics and Gynecology, Dr S N Medical College Jodhpur, Rajasthan. A total of 160 asphyxiated neonates (80 intramural and 80 extramural) were included in the study. A detailed antenatal and perinatal history with obstetrical interventions were recorded. The progress or deterioration in the clinical status of child was noted in hours. Outcome was evaluated in terms of survival, severest Hypoxic Ischaemic Encephalopathy (HIE) stage, time taken to reach non encephalopathic state, requirement of vasopressors and anticonvulsants, ventilator support, hemodynamic stability, time period to attain full enteral feeding, neurological examination at time of discharge and time taken for discharge.Results: Significant difference was observed in the antenatal and perinatal profile, perinatal management and resuscitation, postnatal management, morbidity, mortality and neurodevelopment outcome of extramurally delivered neonates in a peripheral health centre or at home as compared to intramurally delivered neonates in a tertiary institute.Conclusions: It is of paramount importance to have an early referral of asphyxiated neonates to a well equipped NICU using an appropriate well equipped transport unit/ chain so as to improve their outcome

Outcomes of haematology/oncology patients admitted to intensive care unit at The Canberra Hospital

BACKGROUND: Outcomes for haematology/oncology patients have improved; however, determining their suitability for intensive care unit (ICU) admission remains challenging and controversial. AIM: Examine outcomes of patients admitted to an Australian tertiary hospital ICU and explore potential prognostic factors. METHODS: A retrospective review of patients with haematological and solid tumour malignancies non-electively admitted to The Canberra Hospital (TCH) ICU, between January 2008 and December 2012. Patient demographics, cancer details, reasons for ICU admission and Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were collected, and survival rates calculated and correlated with potential prognostic factors. RESULTS Of 205 patients, 113 (55%) had haematological malignancies, and 92 (45%) had solid tumours: 58% male and mean age 60.3 years (standard deviation (SD) 13.4). Eighty-two per cent of solid tumour patients had metastatic disease and 55% received palliative chemotherapy. Primary reasons for ICU admission included sepsis (59%), respiratory distress (37%) and hypotension/shock (18%). Mean APACHE II score was 20.1(SD 0.55); mean length of stay in ICU, 4 days (SD 5.2); ICU survival was 76% with 62% and 41% alive at 30 days and 6 months respectively. Overall 1-year survival was 36%. High APACHE II scores and ≥2 organs failing were significant risk factors for 30-day mortality. CONCLUSION: Short-term outcomes were similar to contemporary studies from a general tertiary hospital setting and better than historical data. Sixty-two per cent of patients were alive 30 days post-ICU admission, with a significant minority alive at 12 months, confirming some patients achieved worthwhile outcomes. Further research is needed to ensure appropriate patient selection and to explore quality of life post ICU

Double blind randomized comparative study of transdermal fentanyl patch for post operative pain relief in major abdominal surgery as a component of multimodal analgesic therapy

Background: There are various methods of alleviating post-operative pain, multimodal analgesia is the recommended practice. Fentanyl patch can also be used in the management of acute postoperative pain. We have done a study to compare the efficacy of fentanyl patch to a placebo patch as a part of multimodal analgesic strategy.Methods: Forty four patients were randomized into two groups. Groups were named as FP (Fentanyl patch) and P (Placebo). The Patch was placed 10-12 hours before surgery and patient was monitored for 72 hours postoperatively for pain by NRS (Numeric Rating Scale). All the patients received regular Paracetamol and Diclofenac Sodium. Tramadol was given as rescue analgesia if the NRS scale was more than 5. Data was analysed using Windows stat version 9.2 from Indostat services.Results: There was statistically significant difference in the consumption of Tramadol in patients with FP group (19.44 mg) as compared to P group (72.22mg) over 72 hours. The Numerical Rating scale was also much lower in the FP group at 8, 16, 24, 32, 40, 48, 56, 64 and 72 hours. Maximum difference in the pain score being at 24 hours for the FP group. No difference in the Sedation, Pruritus, Respiratory depression, Nausea and vomiting scores in the two groups.Conclusions: Transdermal Fentanyl Patch of 25 µg/hr when applied 10-12 hours before surgery provides effective postoperative pain relief after major abdominal surgery as a part of multimodal analgesia

Response prediction of neoadjuvant chemoradiation therapy in locally advanced rectal cancer using CT-based fractal dimension analysis

OBJECTIVES: There are individual variations in neo-adjuvant chemoradiation therapy (nCRT) in patients with locally advanced rectal cancer (LARC). No reliable modality currently exists that can predict the efficacy of nCRT. The purpose of this study is to assess if CT-based fractal dimension and filtration-histogram texture analysis can predict therapeutic response to nCRT in patients with LARC. METHODS: In this retrospective study, 215 patients (average age: 57 years (18-87 years)) who received nCRT for LARC between June 2005 and December 2016 and underwent a staging diagnostic portal venous phase CT were identified. The patients were randomly divided into two datasets: a training set (n = 170), and a validation set (n = 45). Tumor heterogeneity was assessed on the CT images using fractal dimension (FD) and filtration-histogram texture analysis. In the training set, the patients with pCR and non-pCR were compared in univariate analysis. Logistic regression analysis was applied to identify the predictive value of efficacy of nCRT and receiver operating characteristic analysis determined optimal cutoff value. Subsequently, the most significant parameter was assessed in the validation set. RESULTS: Out of the 215 patients evaluated, pCR was reached in 20.9% (n = 45/215) patients. In the training set, 7 out of 37 texture parameters showed significant difference comparing between the pCR and non-pCR groups and logistic multivariable regression analysis incorporating clinical and 7 texture parameters showed that only FD was associated with pCR (p = 0.001). The area under the curve of FD was 0.76. In the validation set, we applied FD for predicting pCR and sensitivity, specificity, and accuracy were 60%, 89%, and 82%, respectively. CONCLUSION: FD on pretreatment CT is a promising parameter for predicting pCR to nCRT in patients with LARC and could be used to help make treatment decisions. KEY POINTS: • Fractal dimension analysis on pretreatment CT was associated with response to neo-adjuvant chemoradiation in patients with locally advanced rectal cancer. • Fractal dimension is a promising biomarker for predicting pCR to nCRT and may potentially select patients for individualized therapy

PDCD1 Polymorphisms May Predict Response to Anti-PD-1 Blockade in Patients With Metastatic Melanoma

A significant number of patients (pts) with metastatic melanoma do not respond to anti-programmed cell death 1 (PD1) therapies. Identifying predictive biomarkers therefore remains an urgent need. We retrospectively analyzed plasma DNA of pts with advanced melanoma treated with PD-1 antibodies, nivolumab or pembrolizumab, for five PD-1 genotype single nucleotide polymorphisms (SNPs): PD1.1 (rs36084323, G>A), PD1.3 (rs11568821, G>A), PD1.5 (rs2227981, C>T) PD1.6 (rs10204225, G>A) and PD1.9 (rs2227982, C>T). Clinico-pathological and treatment parameters were collected, and presence of SNPs correlated with response, progression free survival (PFS) and overall survival (OS). 115 patients were identified with a median follow up of 18.7 months (range 0.26 – 52.0 months). All were Caucasian; 27% BRAF V600 mutation positive. At PD-1 antibody commencement, 36% were treatment-naïve and 52% had prior ipilimumab. The overall response rate was 43%, 19% achieving a complete response. Overall median PFS was 11.0 months (95% CI 5.4 - 17.3) and median OS was 31.1 months (95% CI 23.2 - NA). Patients with the G/G genotype had more complete responses than with A/G genotype (16.5% vs. 2.6% respectively) and the G allele of PD1.3 rs11568821 was significantly associated with a longer median PFS than the AG allele, 14.1 vs. 7.0 months compared to the A allele (p=0.04; 95% CI 0.14 – 0.94). No significant association between the remaining SNPs and responses, PFS or OS were observed. Despite limitations in sample size, this is the first study to demonstrate an association of a germline PD-1 polymorphism and PFS in response to anti-PD-1 therapy in pts with metastatic melanoma. Extrinsic factors like host germline polymorphisms should be considered with tumor intrinsic factors as predictive biomarkers for immune checkpoint regulators

Aromatase expression is increased in BRCA1 mutation carriers

<p>Abstract</p> <p>Background</p> <p>Until recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of <it>BRCA1 </it>gene mutations had not been clearly understood. Of significance is the finding that BRCA1 negatively regulates aromatase expression <it>in vitro</it>. Our objective was to characterise aromatase gene <it>(CYP19A1) </it>and its promoter expression in breast adipose and ovarian tissue in <it>BRCA1 </it>mutation carriers and unaffected controls.</p> <p>Methods</p> <p>We measured aromatase transcripts, total and promoter-specific (PII, PI.3, PI.4) in prophylactic oophorectomy or mastectomy, therapeutic mastectomy, ovarian and breast tissue from unaffected women.</p> <p>Results</p> <p>We demonstrate that the lack of functional BRCA1 protein correlates to higher aromatase levels in 85% of <it>BRCA1 </it>mutation carriers. This increase is mediated by aberrant transcriptional regulation of aromatase; in breast adipose by increases in promoter II/I.3 and I.4-specific transcripts; and in the ovary with elevation in promoter I.3 and II-specific transcripts.</p> <p>Conclusion</p> <p>Understanding the link between BRCA1 and aromatase is significant in terms of understanding why carcinogenesis is restricted to estrogen-producing tissues in <it>BRCA1 </it>mutation carriers.</p