Response to Tyrosine Kinase Inhibitors in Patients with BCR-ABL1 Positive Chronic Myeloid Leukemia; 13.5 Years’ Experience at Patan Hospital, Nepal

Background:Since the advent of Tyrosine Kinase Inhibitor (TKI), well controlled studies in developed world have shown that the life expectancy of patients with CML is comparable to normal people without the disease. But long-term follow up studies are lacking in resource poor setting. Methods:This is a retrospective follow up study looking at the molecular response and resistance to Tyrosine Kinase Inhibitors (TKI) in patients enrolled in the Max Access Program since February 2003 till March 2017. Patients with twoor more BCR-ABL1 levels by Karyotyping/ fluorescent in situ hybridization (FISH) / reverse transcriptase polymerase chain reaction (RT-PCR) were included. At baseline, complete blood count (CBC), renal function test (RFT), and liver function test (LFT) were evaluated. Bone marrow aspiration and biopsy for morphology, cytogenetic analysis by Karyotyping/FISH and/or molecular analysis by RT-PCR were also done if these tests were not performed earlier. FISH or RT-PCR was done on peripheral blood every 3–12 months as necessary if the patient could afford. Patients with warning response/failure underwent BCR-ABL1 Resistance Mutation Analysis (IRMA).Results:Three hundred and forty six (346) patients had two or more BCR-ABL1 monitoring tests done. Optimal response was seen in 49.42%. Similarly, suboptimal response and failure were seen in 16.5% and 34% respectively. Overall Survival is 89.6% (at 1.8 -165 months, mean 62 months) . If only CML related events is considered survival is 95.9%. Seventy seven (77) patients with a total of 80 BCR-ABL1 domain Imatinib Resistance Mutation Analyses (IRMA) showed 19 different types of mutations with the most common being T315I mutation (8 and 19.5%). About 22.25% of the total patients showed resistance to Glivec out of which 10.98% showed mutations. Nine patients underwent trial for treatment free response (TFR) and 5 of them relapsed between 2-8 months.Conclusions:Despite all the odds of having financial problem, accessibility problem due to distances, transportation, etc. and difficulty monitoring with routine BCR-ABL1 and IRMA, our findings show that the outcome of TKI therapy in our CML patients is comparable to well controlled studies done elsewhere. Overall survival, molecular and cytogenetic responses and mutations in our patients who developed resistance as well as TFR are also similar to other studies. The resistance rate of 22.25% is slightly higher compared to other studies in developed world. This is mainly because of poor monitoring due to unavailability of the test including IRMA in our country and affordability until 2012. It proves that TKI is very effective in CML even in a resource-poor, developing country

Prevalence of diabetic retinopathy following a community screening for diabetes.

Diabetic retinopathy is a public health challenge in developing countries including Nepal and is not like other preventable or treatable causes of blindness. The aim of study was to estimate the prevalence of diabetic retinopathy following a community screening for diabetes. A community-based, cross sectional study was designed to screen for diabetes in people age > or =40 years in a semi-urban community of Kathmandu, Nepal. In those individuals with detected diabetes, a comprehensive eye examination was performed by an ophthalmologist and diabetic retinopathy was graded using a standard protocol. 1475 persons were screened for diabetes with a mean age of 54.7 +/- 12 years with sex ratio of 0.69 male per female. Thirty-four subjects were found to have impaired fasting glucose and sixty subjects had diabetes. The prevalence of diabetes mellitus was 4.1% (60) but 6.4% (94) had an abnormal blood sugar level. Fifty-seven diabetic patients visited at-Tilganga Eye Centre for ocular examination. Among examined patients, the prevalence of diabetic retinopathy was 19.3% (11). Only one person had clinically significant macular edema requiring laser therapy. The prevalence of hypertension and cataracts were the same among patients with and without diabetic retinopathy. The prevalence of diabetic retinopathy was low but one of sixteen newly diagnosed diabetics did have evidence of diabetic retinopathy. Eighty-four percent of known diabetics had never had their eyes examined for ocular complications. Community awareness and physician coordination should be emphasized to increase the eye examination rate.

Eliciting knee jerk--a new method of reinforcement.

This study was designed to detect the sensitivity of different methods of eliciting knee jerks and to compare the conventional methods with the newly purposed maneuver. Knee jerk (a deep tendon reflex) was elicited in 123 apparently normal population (77 males and 46 females) with three different methods (1) without applying reinforcement, (2) applying Jendrassik maneuver (strong voluntary contraction of upper limbs) and (3) using the new method of reinforcement--that is by dorsiflexion of ankle joint of the same foot voluntarily as strong as possible on which the jerk would be elicitated. The sensitivity of the method without reinforcement was found to be is 87.8%; that with Jendrassik maneuver was 93.5%, whereas the sensitivity of newly proposed maneuver was 99.2%. Results of the present study have served to demonstrate that elicitation of knee jerk with newly proposed reinforcement maneuver is the best among all three methods.

Comparative study of esmolol and labetalol to attenuate haemodynamic responses after electroconvulsive therapy.

OBJECTIVE: The study was designed to evaluate the hemodynamic effects of Esmolol and labetalol in patients undergoing electroconvulsive therapy. MATERIALS AND METHODS: Ninety patients undergoing electroconvulsive therapy treatment were studied according to randomized, double blind placebo controlled protocol. Ninety patients were divided into three groups with thirty patients in each group. Patients received either Esmolol (1 mg/kg), Labetalol (0.25 mg/kg) or Normal Saline (placebo) intravenously just after induction with propofol. The baseline heart rate and blood pressure were recorded. Hemodynamic parameters before and after drug therapy and after the ECT current application, were recorded at different time intervals. RESULTS: It was found that Esmolol significantly attenuated the degree of tachycardia and hypertension after ECT in comparison with placebo in the first three minutes (p<0.05), whereas the rise in HR and blood pressure was significantly blunted in the labetalol group in comparison to placebo, from three minutes onward till ten minutes. (p<0.05). CONCLUSION: It was concluded that Esmolol is effective in blunting the hemodynamic response after ECT stimulus in the first three minutes after application of the electrical current, whereas Labetalol is effective after five minutes onwards till ten minutes.

Etiological pattern of blepharoptosis among patients presenting in teaching hospital.

The purpose of this study was to find out the etiological pattern of blepharoptosis among patients presenting in BPKLCOS, T.U. Teaching Hospital. This was a hospital based descriptive and cross-sectional study conducted from February 2003 to July 2004. A total of 125 patients with ptosis were evaluated. 78 cases (62.4%) were congenital and 47 cases (37.6 %) were acquired. Congenital simple ptosis and congenital complicated ptosis comprised of 58% and 42% respectively. Among the acquired cause, ptosis due to trauma was the commonest 32%, followed by third cranial nerve palsy 25.5%, myasthenia gravis 17%, aponeurotic 10.7%, chronic progressive external ophthalmoplegia 8.5% etc. Aetiology-wise, myogenic ptosis was the commonest (65.6%) which was followed by neurogenic (16.8%), traumatic (12%) and aponeurotic ptosis (5.6%). Congenital ptosis is more common than acquired ptosis. Myogenic ptosis is the most predominant type of ptosis. Among the congenital ptosis, congenital simple ptosis is more common than congenital complicated ptosis. Among the acquired cases trauma, third cranial nerve palsy and myasthenia gravis are the major attendees.