Dengue fever in hyperglycemic patients: an emerging public health concern demanding eyes on the effective management strategies.

Background and aims: Hyperglycemia, also known as diabetes, is a metabolic disorder characterized by elevated levels of glucose in the bloodstream. It can lead to the prolonged dysfunction, injury, and deterioration of several organs. In addition, dengue is a viral illness transmitted by mosquitoes that has reached epidemic proportions worldwide. In this article, we focused on the severity of comorbidities, difficulties in managing them, and preventive measures meant to lessen the risks associated with comorbidities in diabetic patients with dengue infection. Methods: We explored a number of databases, including PubMed, Scopus, Embase, Web of Science, Google Scholar, and the Cochrane Library, for this review article using various related keywords. Results: The findings of this review article indicate that elderly dengue patients with diabetes should be admitted to the hospital for close observation and early management using fluid therapy. An observed association exists between dengue hemorrhagic fever (DHF) and diabetes, indicating a possible consequence in this specific group. Additionally, patients with diabetes who contract dengue show elevated levels of inflammatory markers. Diabetes mellitus deteriorates the immune system, which exacerbates the progression of dengue fever. Cutting-edge technology and scientific research may assist in addressing the challenges that diabetes and dengue viruses pose in low- and middle-income countries. Implementing innovative diabetic care management is essential to ensuring consistency of care, improving a healthy lifestyle, and lowering patient risk factors and comorbidities. Conclusion: Dengue fever has spread to epidemic levels throughout the world. Inflammatory markers increase and the prevalence of DHF is greater in diabetes individuals with dengue infection. Given the continued growth of dengue in Asian nations, it is imperative that we concentrate our efforts and resources on providing more precise and effective treatment for this emerging issue.

Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder.

PURPOSE: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations. METHODS: Clinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies. RESULTS: We characterize a clinically variable disorder with cardinal features including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a-/- mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition. CONCLUSION: Our studies comprehensively characterise INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation.

Knowledge, attitudes, and practices of anaesthesia personnel towards needle stick injuries in a tertiary care hospital.

The cross-sectional, prospective study was conducted at the Aga Khan University Hospital, Karachi. A questionnaire was distributed amongst anaesthesia personnel, including faculty, residents, medical officers, technicians, recovery room nurses and pain nurses working in the Department of Anaesthesiology for >3 months. Knowledge, attitudes and practices were assessed according to the operational definitions. Of the 162 respondents, 106(65.4%) were males and 56(34.6%) were females. The overall mean age was 31±6.2 years. Adequate knowledge was found in 41(25%) subjects. Overall, 56(35%) respondents reported having had a needle-stick injury, and, among them, 49(87.5%) had a positive attitude. Also, 156(96.3%) participants followed good practices. Although entirely preventable, needle stick injuries were found to be common, indicating the need for proper implementation or revision of existing policies and attainment of safe needle devices.

Identification of new variants in patients with mucopolysaccharidosis in consanguineous Iranian families.

Introduction: Mucopolysaccharidoses are a group of lysosomal storage disorders that include seven types that are classified based on the enzymes that are disrupted. Malfunction of these enzymes leads to the accumulation of glycosaminoglycans (GAGs) in various tissues. Due to genetic and clinical heterogeneity, diagnosing and distinguishing the different types is challenging. Genetic methods such as whole exome sequencing (WES) and Sanger sequencing are accurate methods for detecting pathogenic variants in patients. Methods: Thirty-two cases of mucopolysaccharidosis, predominantly from families with consanguineous marriages, were genetically examined. Out of these, fourteen cases underwent targeted sequencing, while the rest underwent WES. The results of WES were analyzed and the pathogenicity of the variants was examined using bioinformatics tools. In addition, a segregation analysis within families was carried out. Results: In most cases, a pathogenic or likely pathogenic variant was detected. Sixteen previously reported variants and six new variants were detected in the known IDS (c.458G>C, c.701del, c.920T>G), GNS (c.1430A>T), GALNS (c.1218_1221dup), and SGSH (c.149T>C) genes. Furthermore, we discovered a c.259G>C substitution in the NAGLU gene for the first time in three homozygous patients. This substitution was previously reported as heterozygous. Except for the variants related to the IDS gene, which were hemizygous, all the other variants were homozygous. Discussion: It appears that the high rate of consanguineous marriages in the families being studied has had a significant impact on the occurrence of this disease. Overall, these findings could expand the spectrum of pathogenic variants in mucopolysaccharidoses. Genetic methods, especially WES, are very accurate and can be used alone or in conjunction with other diagnostic methods for a more precise and rapid diagnosis of mucopolysaccharidoses. Additionally, they could be beneficial for family screening and disease prevention.

Genotypic variants of the tetrahydrobiopterin (BH4) biosynthesis genes in patients with hyperphenylalaninemia from different regions of Iran.

BACKGROUND: Hyperphenylalaninemia (HPA) is a metabolic disorder classified into phenylalanine-4-hydroxylase (PAH) and non-PAH deficiency. The latter is produced by mutations in genes involved in the tetrahydrobiopterin (BH4) biosynthesis pathway and DNAJC12 pathogenetic variants. The BH4 metabolism, including de novo biosynthesis involved genes (i.e., guanosine 5'-triphosphate cyclohydrolase I (GTPCH/GCH1), sepiapterin reductase (SR/SPR), 6-pyruvoyl-tetrahydropterin synthase (PTPS/PTS)), and two genes that play roles in cofactor regeneration pathway (i.e., dihydropteridine reductase (DHPR/QDPR) and pterin-4α-carbinolamine dehydratase (PCD/PCBD1)). The subsequent systemic hyperphenylalaninemia and monoamine neurotransmitter deficiency lead to neurological consequences. The high rate of consanguineous marriages in Iran substantially increases the incidence of BH4 deficiency. METHODS: We utilized the Sanger sequencing technique in this study to investigate 14 Iranian patients with non-PAH deficiency. All affected subjects in this study had HPA and no mutation was detected in their PAH gene. RESULTS: We successfully identified six mutant alleles in BH4-deficiency-associated genes, including three novel mutations: one in QDPR, one in PTS, and one in the PCBD1 gene, thus giving a definite diagnosis to these patients. CONCLUSION: In this light, appropriate patient management may follow. The clinical effect of reported variants is essential for genetic counseling and prenatal diagnosis in the patients' families and significant for the improvement of precision medicine.

Sleep Pattern Changes in Patients Who Are Scheduled for Cardiac Surgery.

Introduction Surgery patients frequently experience sleep deprivation, which is regarded as a stress factor during the perioperative period and can cause physical discomfort, exhaustion, and even postoperative pain. There is a dearth of information on preoperative sleep habits and the consequences that may result. There are both subjective and objective ways to rate the quality of your sleep. We chose the Pittsburgh Sleep Quality Index (PSQI), which employs a questionnaire to provide crucial information on issues like sleep length, efficiency, and interruption. Lower sleep quality is correlated with higher PSQI scores. Study objective Our study aimed to assess the changes in the sleep pattern of cardiac disease patients before cardiac surgery and compare these changes with baseline sleep patterns. Methods This prospective survey was carried out after ethical review committee approval at the Department of Anesthesia, Aga Khan University Hospital. Consent was obtained from all patients undergoing cardiac surgery. Strict inclusion and exclusion criteria were followed. All patients aged 25 to 65 who came from home for elective cardiac surgery under general anesthesia were included. At the same time, patient demographics were noted. Additionally, a printed PSQI questionnaire was distributed to each participant. The native Urdu language was also translated into this questionnaire. The patient was given an explanation of this form by a medical professional. This questionnaire was filled out by the patients on the surgical floor or preoperative area before premedication. The PSQI questionnaire was used to assess baseline sleeping patterns, and then the same questions were asked about the period between decisions for the date of surgery and the time of admission for surgery. Results A total of 83 patients participated in the study. The mean age of the patient was 57 (±13.0), out of which 67 (80.7%) were males and 16 (19.3%) were females. The most common surgeries were coronary artery bypass (CABG) surgery 63 (77.8%), followed by valve replacement nine (11.1%). The overall mean PSQI score was higher (5.27) once the surgery date was decided as compared to the baseline (4.84), but it did not reach the statistically significant level (p-value 0.411). Sleep latency (time to fall asleep while in bed) was the only variable statistically significant between baseline (26.1 (±35.0) and after the surgery date has been finalized (36.1 (±46.6)). No significant differences were found in other variables like sleep quality (feeling of being well-rested), sleep duration (hours of actual sleep), sleep efficiency (sleep efficiency is the ratio of the amount of total time asleep versus the total time in bed), and sleep disturbance (problem initiating and maintaining sleep). Total bedtime was also reduced at night before surgery but did not achieve a significant level. The logistic regression model demonstrated that age, gender, and type of surgery did not influence sleep quality. Conclusion In the present study, lower sleep quality was observed before cardiac surgery, but it did not reach a statistically significant level when compared with baseline. Sleep latency (time to fall asleep while in bed) was significantly prolonged compared to baseline. We could not find any association between quality of sleep and variables like age, gender, and type of surgery.

Frequency and prognostic influence of ASXL1 mutations and its potential association with BCR-ABL1 transcript type and smoke in chronic myeloid leukemia patients.

BACKGROUND: Heterogeneous response to tyrosine kinase inhibitors (TKIs) and progress to advance phases, still is a significant clinical problem. These are attributed to additional mutations in mutated non-ABL1 genes. we aimed to determine prognostic effects of ASXL1 mutations as a biomarker for diverse treatment response and disease progression to aid clinical management. METHODS: We performed ASXL1 gene mutational screening in 80 Ph+CML patients at different phases and 10 healthy control by direct sequencing method. Multiplex and qRT-PCR, standard chromosome banding analysis were used to determine BCR-ABL1 transcript type, molecular and cytogenetic responses respectively. RESULTS: overall, four type mutations were identified in 11.25% of the patients. There was significant difference regarding mutation frequency between chronic and advance phases (P = 0.0002), sokal risk score (P = 0.0001), smoking (P = 0.02) and mean of during time of imatinib treatment (P = 0.009) between patients with and without ASXL1 mutations. ASXL1 mutations frequency had a bias toward younger than older and women than men, but no significant (P > 0.05). ASXL1 mutations were found more recurrently in patients carrying ABL1 KD mutations (P = 0.003). The risk of increasing resistance and disease progression in patients with ASXL1 mutations was 32 and 63 fold higher than those without mutations respectively (P = 0.01; P = 0.0002). The risk of ASXL1 mutations presence in patients with b2a2 transcript type was much higher than b3a2 type (P = 0.02, OR = 10). CONCLUSION: Our findings suggest that ASXL1 mutations may be favorable predictive biomarkers to determine the best TKI for each patient, and to prevent CML progression.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'.

Hyaluronic acid/alginate-based biomimetic hydrogel membranes for accelerated diabetic wound repair.

The study aims to develop a new multifunctional biopolymer-based hydrogel membrane dressing by adopting a solvent casting method for the controlled release of cefotaxime sodium at the wound site. Sodium alginate enhances collagen production in the skin, which provides tensile strength to healing tissue. Moreover, the significance of extracellular molecules such as hyaluronic acid in the wound the healing cascade renders these biopolymers an essential ingredient for the fabrication of hydrogel membranes via physical crosslinking (hydrogen bonding). These membranes were further investigated in terms of their structure, and surface morphology, as well as cell viability analysis. A membrane with the most suitable characteristics was chosen as a candidate for cefotaxime sodium loading and in vivo analysis. Results show that the 3D porous nature of developed membranes allows optimum water vapor and oxygen transmission (>8.21 mg/mL) to divert excessive wound exudate away from the diabetic wound bed, MTT assay confirmed cell viability at more than 80%. In vivo results confirmed that the CTX-HA-Alg-PVA hydrogel group showed rapid wound healing with accelerated re-epithelization and a decreased inflammatory response. Conclusively, these findings indicate that CTX-HA-Alg-PVA hydrogel membranes exhibit a suitable niche for use as dressing membranes for healing of diabetic wounds.

Association of ABCB1, ABCG2 drug transporter polymorphisms and smoking with disease risk and cytogenetic response to imatinib in chronic myeloid leukemia patients.

BACKGROUND: Despite acceptable results of imatinib in the treatment of chronic myeloid leukemia (CML), some patients fail to acquire a complete cytogenetic response (CCyR), which may be caused by polymorphisms in the pharmacogenetic genes. The study aimed to evaluate the association of two polymorphisms in the ABCB1 and ABCG2 genes with cytogenetic response to imatinib and the risk of CML development. METHODS: We genotyped ABCB1 (c .2677G/T/A) and ABCG2 (c .421C/A) polymorphisms by PCR-RFLP, T-ARMS-PCR methods in 111 patients with CML and 102 sex- and age-matched healthy subjects. CCyR was determined by standard chromosome banding analysis (CBA). RESULTS: Analysis of polymorphisms showed significant association of ABCG2 c.421CA genotype (p < 0.0001; OR = 0. 17), and ABCG2c.421A allele (p < 0.0001; OR = 0.31) with decreased risk of CML. Moreover, ABCB1c.2677GT- ABCG2c.421CC combined genotype (p = 0.017; OR = 4.20) was associated with increased risk of CML. Analysis of the joint effect of SNP-smoking combination showed that smoker subjects with the ABCB1c.2677GG/GT (p = 0.001; OR = 15.96, p = 0.001; OR = 8.13, respectively) or ABCG2c.421CC genotypes (p = 0.001; OR = 5.82) had the increased risk of CML, while the risk of the CML in non-smokers carrying the ABCG2c.421CA (p < 0.0001; OR = 0. 18) genotype was strongly decreased compared with reference group. Regarding drug response, ABCG2c.421 CC/CA genotypes in the smoker patients were associated with an increased risk of resistance to imatinib (p < 0.0001; OR = 7.02, p = 0.018; OR = 4.67, respectively). CONCLUSION: Our results suggest the impact of ABCG2c .421C/A polymorphism on CML development, and smoking may have a synergistic role in the risk of CML and resistance to imatinib.

Multiplex Snapshot minisequencing for the detection of common PAH gene mutations in Iranian patients with Phenylketonuria

Background: Phenylketonuria is a common inborn defect of amino acid metabolism in the world. This failure is caused by an autosomal recessive insufficiency of the hepatic enzyme hyperphenylalaninemia (PAH), which catalyzes the irreversible hydroxylation of phenylalanine to tyrosine. More than 1,040 different disease-causing mutations have already been identified in the PAH gene. The most prominent complication of Phenylketonuria, if not diagnosed and treated, is severe mental retardation. Hence, early diagnosis and initiation of nutritional therapy are the most significant measures in preventing this mental disorder. Given these data, we developed a simple and rapid molecular test to detect the most frequent PAH mutations. Methods: Multiplex assay was developed based on the SNaPshot minisequencing approach to simultaneously perform genotyping of the 10 mutations at the PAH gene. We optimized detection of these mutations in one multiplex PCR, followed by 10 single-nucleotide extension reactions. DNA sequencing assay was also used to verify genotyping results obtained by SNaPshot minisequencing. Result: All 10 genotypes were determined based on the position and the fluorescent color of the peaks in a single electropherogram. Sequencing results of these frequent mutations showed that by using this method, a 100% detection rate could be achieved in the Iranian population. Conclusion: SNaPshot minisequencing can be useful as a secondary test in neonatal screening for HPA in neonates with a positive screening test, and it is also suitable for carrier screening. The assay can be easily applied for accurate and time- and cost-efficient genotyping of the selected SNPs in various population.

Whole exome sequencing reveals several novel variants in congenital disorders of glycosylation and glycogen storage diseases in seven patients from Iran.

BACKGROUND: Congenital disorder of glycosylation (CDG) and Glycogen storage diseases (GSDs) are inborn metabolic disorders caused by defects in some metabolic pathways. These disorders are a heterogeneous group of diseases caused by impaired O- as well as N-glycosylation pathways. CDG patients show a broad spectrum of clinical presentations; many GSD types (PGM1-CDG) have muscle involvement and hypoglycemia. METHODS: We applied WES for all seven patients presenting GSD and CDG symptoms. Then we analyzed the data using various tools to predict pathogenic variants in genes related to the patients' diseases. RESULTS: In the present study, we identified pathogenic variants in Iranian patients suffering from GSD and CDG, which can be helpful for patient management, and family counseling. We detected seven pathogenic variants using whole exome sequencing (WES) in known AGL (c.1998A>G, c.3635T>C, c.3682C>T), PGM1 (c.779G>A), DPM1 (c.742T>C), RFT1 (c.127A>G), and GAA (c.1314C>A) genes. CONCLUSION: The suspected clinical diagnosis of CDG and GSD patients was confirmed by identifying missense and or nonsense mutations in PGM1, DPM1, RFT1, GAA, and AGL genes by WES of all 7 cases. This study helps us understand the scenario of the disorder causes and consider the variants for quick disease diagnosis.

The Use of Lumbar Drain for Spinal Cord Protection in a Thoraco Abdominal Aortic Aneurysm Surgery.

Thoraco-abdominal aortic aneurysm (TAAA) repair is a complicated and challenging surgery with high chances of unpredictable post-operative outcomes. This is a case of a 56-year man electively admitted for De Bakey type III TAAA repair. The case was done with the one-lung ventilation (OLV) technique by using a bronchial blocker. The other unique thing which was done in this case was the use of a lumbar drain for spinal cord protection. The patient had a prolonged hospital stay but ultimately recovered and was discharged home after two and a half months. Key Words: Lumber drain, Spinal cord injury, Aortic aneurysm surgery.

Hb Narges Lab, a Novel Hemoglobin Variant of the ß-Globin Gene.

In this study, we describe a new missense variant on the ß-globin gene in a heterozygous form in a female individual. Standard methods were used to determine red blood cell indices and perform hemoglobin analyses. Molecular studies were performed on the genomic DNA isolated from peripheral blood cells. Beta-globin genes were amplified and sequenced. We report a novel mutation on the ß-globin gene (HBB), c.134 C>T; p.S44F variant, in the heterozygote state which was detected in a female of Persian ethnic origin in the Khuzestan province, southern Iran, that we named Hb Narges Lab (HbNL) variant. This mutation was predicted to be disease-causing in all except one in silico prediction tools. This variant was reported for the first time worldwide, had no shown hematological abnormalities but should be considered when inherited in the compound heterozygous form with ß- thalassemia (ß0-thal) carrier, which might result in the phenotype of thalassemia intermedia.

Genotype-phenotype correlation in patients with deletional and nondeletional mutations of Hb H disease in Southwest of Iran.

We studied the alpha-globin gene genotypes, hematologic values, and transfusion-dependence of patients with Hb H disease. Molecular characterization of alpha-thalassemia was performed. We identified 120 patients with Hb H disease. Of these patients, 35 (29.16%) had deletional form of Hb H disease, and 85 (70.83%) had different form of non-deletional Hb H disease. The most frequently observed Hb H genotypes were --Med/-α3.7 in 33 patients (27.5%), αCD19(-G) α/αCD19(-G) α in 25 cases (20.83%), αpolyA2α/αpolyA2α in 15 (12.5%), and αpolyA1α/αpolyA1α in 13 (10.83%) respectively. The probability of receiving at least one transfusion blood in deletional form was observed in 3 of 35 (8.57%) patients which just seen in 3 of 33 (9%) patients with --Med/-α3.7 genotype. This form was also observed in 8 of 85 (9.4%) patients in non-deletional Hb H diseases which five of them had Med deletion in compound with alpha globin point mutations. Nondeletional Hb H disease was more severe than deletional Hb H disease requiring more blood transfusions. We can recommend that Med deletion in compound with alpha-globin point mutations, polyA1 and constant spring in homozygous form needs to be taken into consideration when offering counseling to high-risk couples.

Influence of Preoperative Anxiety Level on Postoperative Pain After Cardiac Surgery.

Background Preoperative anxiety is generally neglected in the evaluation of cardiac surgery patients due to various reasons including insufficient literature and lack of simple assessment tools. In addition to this, the association between anxiety and postoperative complications including pain has been scarcely studied. The present study was designed to assess preoperative anxiety levels in all patients coming for cardiac surgery and then evaluate the effect of different levels of anxiety on postoperative pain scores. Methods This prospective cohort study was conducted in a single university hospital from March 2018 to December 2019. One hundred consecutive cardiac surgery patients between the ages of 18-65 years were enrolled in this study. The level of preoperative anxiety (assessed by State Anxiety Inventory) and its effect on postoperative pain and morphine consumption was assessed. Results The average age of the patients was 58.24±10.03 years of which 68% were male and 32% were female. Preoperative mild anxiety was observed in 64% of patients and moderate to severe anxiety in 36% of patients. Post-operative mean pain score was significantly high in the moderate to severe anxiety group as compared to the mild anxiety group [Mean pain difference =1.64 (95%CI: 1.38-1.89) p=0.0005], [Mean pain difference =0.51 (95%CI: 0.29-0.73) p=0.0005] at 12 hours and 24 hours respectively. Intraoperative and postoperative morphine consumption was significantly high in patients with moderate to severe anxiety. Conclusions Patients with moderate to severe anxiety before cardiac surgery experienced higher pain scores at a post-operative period which is significantly different from the mild anxiety group. Intraoperative and postoperative analgesic requirements were also significantly increased.

Comparison of perioperative analgesia between intravenous paracetamol and fentanyl for rigid hysteroscopy: A randomised control trial.

OBJECTIVE: To compare efficacy of intravenous paracetamol and fentanyl for intra-operative and post-operative analgesia in patients undergoing rigid hysteroscopy. METHOD: The prospective randomised control trial was conducted at Aga Khan University Hospital, Karachi, from October 2016 to June 2017, and comprised patients aged 18-65 years with American Society of Anesthesiologists grade I or II undergoing hysteroscopy who were randomised into paracetamol group P and fentanyl group F. Anaesthesia induction technique was standardised and analgesia in group P was paracetamol 15mg/Kg administered 15-30 minutes pre-surgery, and in group F, it was fentanyl 2mcg/kg administered at induction of anaesthesia. Intra-operative pain was assessed by changes in heart rate, systolic, diastolic and mean arterial blood pressure, and post-operative pain was assessed using the visual analogue scale. Data was analysed using SPSS 19. RESULTS: Of the 60 patients, there were 30(50%) in each of the two groups. Baseline parameters were similar in the groups except for age differences (p<0.011). In group P, mean systolic blood pressure at 10,15, 20, 25 and 30 minutes, mean diastolic blood pressure at 20, 25 minutes, and mean arterial blood pressure at 20 minutes were statistically significant (p<0.05) compared to group F. The mean heart rate was not significant between the groups (p>0.05). Post-operative pain scores were similar at 0, 15 and 30 minutes (p>0.05). Rescue analgesia was needed in 3(10%) patients in each group on arrival in the recovery room. CONCLUSIONS: Intravenous paracetamol offered analgesic efficacy similar to fentanyl for rigid hysteroscopy in ambulatory surgery.

Association of SLC22A1,SLCO1B3 Drug Transporter Polymorphisms and Smoking with Disease Risk and Cytogenetic Response to Imatinib in Patients with Chronic Myeloid Leukemia.

OBJECTIVE: To determine whether polymorphisms of SLC22A1 and SLCO1B3 genes could predict imatinib (IM) response and chronic myeloid leukemia (CML) risk. METHODS: We genotyped SLC22A1 (c.480G > C, c.1222A > G) and SLCO1B3 (c.334T > G, c.699G > A) polymorphisms in 132 patients with CML and 109 sex- and age-matched healthy subjects. The patients were evaluated for cytogenetic response by standard chromosome banding analysis (CBA). RESULTS: Polymorphism analysis showed significant increased risk of IM resistance for SLC22A1c.1222AG (P = .03; OR = 2.2), SLCO1B3c.334TT/TG genotypes (P = .007; OR = 4.37) and 334T allele (P = .03; OR = 2.86). The double combinations of SLC22A1c.480CC and c.1222AG polymorphisms with SLCO1B3c.334TT/TG were significantly associated with complete cytogenetic response (CCyR) (P <.05; OR> 7). The interaction between all polymorphisms and smoking were associated with CML development and IM resistance (P ≤.04; OR> 3). CONCLUSIONS: Our study results suggest the influence of SLC22A1 and SLCO1B3 polymorphisms and the interaction of smoking on CML development and IM response.

Quality assurance audit in adult cardiac anaesthesia.

OBJECTIVE: To assess different anaesthesia-related quality indicators during adult cardiac surgery. METHODS: The prospective clinical audit was conducted at the Aga Khan University Hospital, Karachi, from October 2016 to March 2017, and comprised all adult patients scheduled for cardiac surgery. Different anaesthesia-related quality indicators were observed during the pre-induction phase, before the cardiopulmonary bypass, during the procedure, and post-surgery till the transfer from the operating room to the cardiac intensive care unit. Data was analysed using SPSS 19. RESULTS: Of the 264 patients, 217(82.2%) had complete record; 160(73.7%) males and 57(26.3%) females. The overall mean age was 56.56±12.46 years. In the pre-induction phase, difficult intravenous and invasive line access was seen in 42(19.3%) patients. Inappropriate information in the preoperative form was found in 6(2.8%) patients, and preoperative drugs for anxiolysis were used in 145(66.8%) patients. Haemodynamic issues were significant during the surgery in 15(6.9%) patients. In the post-surgery period, abnormal activated clotting time was found in 17(7.8%) patients, while monitoring problems were faced in 7(3.2%) cases during transfer to cardiac intensive care unit. CONCLUSIONS: It will help to develop quality improvement policies to enhance patient safety, satisfaction and better outcome.