Stem Cell Transplantation in Glanzmann's Thrombasthenia: A Report of Two Adult Patients.

Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder characterised by mucocutaneous bleeding. At molecular level, defect in platelet receptor glycoprotein (GP) IIb/IIIa leads to defective platelet aggregation. Anti-fibrinolytic agents, platelet transfusions, and factor rVIIa are used for prophylaxis before invasive procedures and treatment of bleeding events. Allogeneic stem cell transplant is the only curative option. Here, we report cases of two adult male patients who underwent matched sibling donor stem cell transplantation for GT with recurrent bleeding requiring platelet and red cell transfusions. Both showed marked improvement in quality of life. To conclude, stem cell transplant is a viable treatment option for severe, difficult-to-control cases of GT. Key Words: Platelet disorders, Hematopoietic stem cell transplantation, Thrombasthenia.

Biocompatibility and Physiological Thiolytic Degradability of Radically Made Thioester-Functional Copolymers: Opportunities for Drug Release.

Being nondegradable, vinyl polymers have limited biomedical applicability. Unfortunately, backbone esters incorporated through conventional radical ring-opening methods do not undergo appreciable abiotic hydrolysis under physiologically relevant conditions. Here, PEG acrylate and di(ethylene glycol) acrylamide-based copolymers containing backbone thioesters were prepared through the radical ring-opening copolymerization of the thionolactone dibenzo[c,e]oxepin-5(7H)-thione. The thioesters degraded fully in the presence of 10 mM cysteine at pH 7.4, with the mechanism presumed to involve an irreversible S-N switch. Degradations with N-acetylcysteine and glutathione were reversible through the thiol-thioester exchange polycondensation of R-SC(═O)-polymer-SH fragments with full degradation relying on an increased thiolate/thioester ratio. Treatment with 10 mM glutathione at pH 7.2 (mimicking intracellular conditions) triggered an insoluble-soluble switch of a temperature-responsive copolymer at 37 °C and the release of encapsulated Nile Red (as a drug model) from core-degradable diblock copolymer micelles. Copolymers and their cysteinolytic degradation products were found to be noncytotoxic, making thioester backbone-functional polymers promising for drug delivery applications.

Relationship between cerebrospinal fluid protein level and electrophysiologic abnormalities in the acute inflammatory demyelinating polyradiculoneuropathy variant of Guillain-Barré syndrome.

Objective: Guillain-Barré syndrome (GBS) is an autoimmune disease characterized by weakness in limbs or cranial nerve innervated muscles. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is the most common variant. Electrophysiologic abnormalities and elevated cerebrospinal fluid (CSF) protein are frequently present in AIDP, but the relationship between these two parameters is not well known. We aimed to fill this gap by studying this relationship. Methods: This was a prospective cross-sectional study conducted for two years in the Department of Neurology, Dr. Ruth K. M. Pfau Civil Hospital, Karachi, Pakistan. All 90 adult patients with the AIDP variant of GBS were selected. Nerve conduction studies were performed to determine the degree of demyelination through the four electrophysiologic demyelination criteria. The CSF sample was sent to lab immediately after lumbar puncture. SPSS version 20.0 was used. The CSF protein level was measured with mean ±SD. Demyelination criteria were measured in frequency and percentages. Chi-square test was applied to a number of demyelination criteria and T-test/ANOVA was applied on mean CSF protein level. Results: We found a mean CSF protein of 37.41 mg/dl (±3.69) with one demyelination criterion, 81.87 mg/dl (±17.39) with two demyelination criteria, 119.75 mg/dl (±31.42) with three demyelination criteria, and 134.00 mg/dl (±42.87) with four demyelination criteria (P-value <0.001). Conclusion: This study demonstrates a significant relationship between CSF protein levels and degree of demyelination in the AIDP variant of GBS. This is an under-researched area in GBS and this study adds favorably to limited data in this regard.

Association Between Hyperuricemia and Acute Ischemic Stroke in Patients at a Tertiary Care Hospital.

Introduction Stroke is the most debilitating of neurologic diseases. The rationale of the current study was to determine the association between hyperuricemia and ischemic stroke to establish a local perspective. Methods A total of 148 patients at a tertiary care hospital in Pakistan who fulfilled the inclusion criteria were enrolled in the study and then equally distributed into two study groups consisting of cases and controls (n = 74 in each group). In this study, there were 36 (48.6%) participants in the case group with hyperuricemia and ischemic stroke and 18 (24.3%) participants in the control group with hyperuricemia. The mean and standard deviations were computed for quantitative variables such as age, body mass index (BMI), and duration of stroke. Frequencies and percentages for the qualitative variables such as gender, hypertension, type 2 diabetes (T2D), dyslipidemia, smoking status, socioeconomic status, educational level, and hyperuricemia were calculated. The chi-square test was applied to compare both groups, with p ≤ 0.05 indicating significance. The odds ratio was also calculated to determine the association between case and control. Effect modifiers were controlled through stratification of age, gender, BMI, duration of stroke, hypertension, T2D, dyslipidemia, socioeconomic status, educational level, and smoking status to determine the effect of these on outcome variables. A post-stratification chi-square test was applied, with p ≤ 0.05 indicating statistical significance. Results In our study, stratification of hyperuricemia into cases and controls was performed for age, gender, T2D, hypertension, dyslipidemia, smoking status, socioeconomic status, and educational status. The maximum results were significant, with high strength of association between both groups. In the case group, the frequency of elevated uric acid was significantly higher than that of the control group. A comparison of hyperuricemia indicated p = 0.002, with an odds ratio of 2.95, which showed that elevated uric acid could be taken as a predictor of ischemic stroke. The uric acid level was significantly higher in men than in women. Additionally, hyperuricemia was associated with dyslipidemia. In patients with ischemic stroke, there was a significant association between serum uric acid level and T2D, hypertension, and smoking. Conclusions This study showed that the prevalence of hyperuricemia in patients with ischemic stroke was significantly higher as compared to the healthy population. Hyperuricemia can be considered as a risk factor for ischemic stroke because of its high prevalence in ischemic stroke patients. Our study explored the relationship between stroke and hyperuricemia and enabled increased understanding for caregivers so that effective management plans can be formulated for patients with ischemic stroke to prevent adverse outcomes.

Etiology and Types of Seizures in Patients Presenting to a Tertiary Care Hospital in Karachi: A Cross-Sectional Study.

Introduction Epilepsy is a burdensome disorder for affected individuals and community. There is limited data available on the epidemiological aspects of seizures in Pakistan and further research is necessary. We aimed to fill this gap by studying this information in epilepsy patients presenting to our neurology department. The purpose of this study is to evaluate the causes and types of seizures among the target population. Method This is a cross-sectional study conducted at the Department of Neurology, Dr. Ruth K.M. Pfau Civil Hospital Karachi. In this study we evaluated the causes and types of seizures among patients presenting to our department during the two-year study duration (January 2018-December 2019). Informed consent was taken. Detailed history was taken including features of seizure episodes, age at first seizure, family history and comorbid conditions. Relevant investigations were carried out. The data was compiled to deduce the relevant information using SPSS v20.0. T-test and Chi-square were used for analyzing the data. Results A total of 996 patients presented during the study duration. Primary seizures were found in 58% cases while secondary seizures were found in 42% cases. This distribution was more equal in children with 49.6% primary seizures and 50.4% secondary seizures; the gap widened in adults with 64.3% primary seizures and 35.7% secondary seizures. The most common cause of secondary seizures was neonatal encephalopathy which was present in 18.7% patients, followed by traumatic head injury in 18.2% patients. Central nervous system (CNS) infection was the cause in 17.9% patients, cerebral tumors in 14.1% patients, stroke in 11.5%, metabolic encephalopathy in 7.4%, febrile seizures in 6.5% and CNS malformations in 5.7% patients. The top three causes in children were neonatal encephalopathy (28.3%), CNS infections (19.3%) and febrile seizures (12.7%). Adults with secondary seizures were diagnosed most often with head trauma (25.2%), cerebral tumors (19.9%) and stroke (18.4%) as causative factors. The most common type of seizures was generalized onset tonic-clonic seizures which was found in 73.0% patients followed by focal to bilateral tonic-clonic seizures in 8.9% patients. Other types of seizures included focal aware seizures in 5.0%, mixed seizure types in 4.2%, focal impaired awareness seizures in 3.1%, absence seizures in 2.7%, myoclonic seizures in 2.0% and atonic seizures in 1.0% patients. Seizures in children were mostly generalized onset tonic-clonic seizures (75.4%), mixed seizure types (5.7%) and focal to bilateral tonic-clonic seizures (5.2%). In adults the three most common types corresponded to the overall result: generalized onset tonic-clonic seizures (71.2%), focal to bilateral tonic-clonic seizures (11.6%) and focal aware seizures (6.6%). Conclusion We found that the most common cause of seizures overall in our study population was primary seizures, though primary and secondary seizures were more evenly present in children. Among secondary causes neonatal encephalopathy stood out as the most common cause in children; head trauma was the predominant cause in adults. Most common type of seizures overall and in adults was generalized onset tonic-clonic seizures, followed by focal to bilateral tonic-clonic and focal aware seizure types. Pediatric patients presented most often with generalized onset tonic-clonic seizures, followed by mixed seizure types and focal to bilateral tonic-clonic seizures.

Cost of Investigating Neurological Disease: Experience of a Tertiary Care Center in Karachi, Pakistan.

INTRODUCTION:  Neurological disorders, structural or functional, are prevalent all over the world and are accompanied by physical and social morbidity. In this study, we aimed to calculate the cost of investigating neurological disorders and compare the costs incurred in a government hospital with that in a private hospital. MATERIALS AND METHODS:  This study was conducted at the Dr. Ruth KM Pfau Civil Hospital, Karachi, Pakistan. One hundred patients were enrolled in the study; 10 each investigated for epilepsy, cerebrovascular accidents (CVAs), headache, neuropathy, myopathy, cranial nerve palsies, movement disorders, demyelinating diseases, central nervous system (CNS) infections, and dementia. Receipts and records in the patients' medical history were used for the calculation of the cost of procedures, which was then compared with the costs of these investigations in a private hospital. A bottom-up costing approach was taken with individual costs being estimated and then being grouped to calculate the overall economic burden of the disorders. Data were analyzed using IBM SPSS version 23.0. One-way analysis of variance (ANOVA) was done to compare the mean cost (taken by the patient, covered by the government, total cost in the government hospital, and total cost in the private hospital) across diseases in government and private hospitals separately. Pearson correlation and scatter plot were also done to study the cost in private and public hospitals. p-values less than 0.05 were considered statistically significant. The margin of error in the study was 5%. RESULTS:  The mean age was 38.2 ± 20.5 years. Some 51% data were received from female samples. The mean income of samples was 13863.6 ± 9715.9 Pakistani Rupees (PKR) or 78.38 ± 58.29 United States Dollars (USD). The mean cost covered by government hospitals was 8866.0 ± 5071.0 PKR (53.19 ± 30.42 USD) per patient, whereas in government hospitals patients were charged on average 2662.9 ± 3774.7 PKR (16 ± 22.65 USD), while in private hospitals patients paid on average 29041.3 ± 12992.6 PKR (174.21 ± 78 USD). CONCLUSION:  The costs of investigations in private hospitals were approximately three times the costs in government hospitals. The maximum cost was generated by patients being investigated for demyelinating disorders. Investigations conducted in government-run hospitals are more cost effective and these institutions should receive increased funding to cater to the maximum number of patients.

Clinical Features Indicating the Need for Mechanical Ventilation in Patients with Guillain Barre Syndrome.

Background Guillain Barre Syndrome (GBS) is an immune-mediated inflammatory polyradiculoneuropathy. Respiratory failure is one of its recognized and most dreaded complications, requiring ventilatory assistance. Early recognition of distinct clinical predictors of mechanical ventilation may help in the better management of GBS patients in our setup. Objective To determine the clinical predictors indicating the need for mechanical ventilation in patients with Guillain Barre Syndrome and to compare the presenting features in patients who require mechanical ventilation and who do not. Method It was a prospective observational study. A total of 100 consecutive patients, over the period of one year, were included in this study. All patients were clinically examined for limb weakness, neck weakness, bulbar and facial nerve involvement, and followed up till seven days of hospitalization for whether the patient required mechanical ventilation or not. Results were recorded on a specifically designed proforma. Data were entered and analyzed using SPSS version 20.0 (IBM Corp., Armonk, NY, US). Results Out of 100 patients, 13% required mechanical ventilation. When clinical presentations were compared in patients who required mechanical ventilation and those who did not, a shorter interval between the onset of symptoms and the attainment of maximal disability, facial weakness, bulbar dysfunction, and neck weakness turned out to be significant factors (p-value<0.000). Conclusion According to these significant outcomes of our study, the course of patients with GBS leading to mechanical ventilation can be predicted on the basis of clinical presentations. So we can recommend that shorter time duration between symptom onset and peak disability, along with the presence of facial, bulbar, and neck weakness, should be taken as an indication of impending respiratory failure.

Pseudoaneurysm of Left proximal Common Carotid Artery following penetrating trauma.

A 33-year male with history of penetrating trauma to left upper chest in 2006, presented through Medical unit to Radiology Department with complain of hemoptysis. Chest X-ray showed a soft tissue lesion in left upper lobe with a linear metallic foreign body. Contrast enhanced CT scan of chest and later CTA was performed which showed a saccular aneurysm arising from mediastinal part of left common aortic artery surrounded by thrombosis with a cylindrical linear metallic foreign body. He was planned for endovascular repair with stenting which he could not afford due to financial constraints. He is currently on conservative follow up. Vascular lesions can be serious complications resulting from blunt or penetrating trauma, when presenting with hemoptysis due to pseudaoneurysms formation even after so many years of trauma.

RETRACTED: Mycoplasma synoviae vaccine modifies virus shedding and immune responses of avian influenza (H9N2) infection in commercial layers.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The authors retract the above paper due to: 1) conflict of interest among the authors; and 2) addition of co-author Dr. Muhammad Younus without his knowledge or permission. The authors apologize for these two grave mistakes.

Quality of life after stroke in Pakistan.

BACKGROUND: There is very little information about the quality of life (QOL) of stroke survivors in LMIC countries with underdeveloped non communicable health infrastructures, who bear two thirds of the global stroke burden. METHODOLOGY: We used a sequential mix methods approach. First, a quantitative analytical cross-sectional study was conducted on 700 participants, who constituted 350 stroke survivor and their caregiver dyads. QOL of stroke survivor was assessed via Stroke Specific Quality of Life Scale (SSQOLS) whereas QOL of caregivers was assessed through RAND-36. In addition; we assessed complications, psychosocial and functional disability of stroke survivors. Following this quantitative survey, caregivers were qualitatively interviewed to uncover contextually relevant themes that would evade quantitative surveys. Multiple linear regression technique was applied to report adjusted ß-coefficients with 95% C.I. RESULTS: The QOL study was conducted from January 2014 till June 2014, in two large private and public centers. At each center, 175 dyads were interviewed to ensure representativeness. Median age of stroke survivors was 59(17) years, 68% were male, 60% reported depression and 70% suffered post-stroke complications. The mean SSQOLS score was 164.18 ± 32.30. In the final model severe functional disability [adjß -33.77(-52.44, -15.22)], depression [adjß-23.74(-30.61,-16.82)], hospital admissions [adjß-5.51(-9.23,-1.92)] and severe neurologic pain [adjß -12.41(-20.10,-4.77)] negatively impacted QOL of stroke survivors (P < 0.01). For caregivers, mean age was 39.18 ± 13.44 years, 51% were female and 34% reported high stress levels. Complementary qualitative study revealed that primary caregivers were depressed, frustrated, isolated and also disappointed by health services. CONCLUSION: The QOL of Stroke survivors as reported by SSQOLS score was better than compared to those reported from other LMIC settings. However, Qualitative triangulation revealed that younger caregivers felt isolated, depressed, overwhelmed and were providing care at great personal cost. There is a need to develop cost effective holistic home support interventions to improve lives of the survivor dyad as a unit. TRIAL REGISTRATION: NCT02351778 (Registered as Observational Study).