Global Neurosurgical Challenges: A Focus on Central Asia.

OBJECTIVE: To evaluate the current state of neurosurgical care in Central Asia, identify the challenges and advancements, and propose recommendations to improve neurosurgical capabilities and access in Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. METHODS: A comprehensive review of the neurosurgical infrastructure, availability of neurosurgeons, technological advancements, and healthcare policies in the five Central Asian countries. Analysis included published literature, healthcare reports, and expert opinions to assess the state of neurosurgical care and identify areas for improvement. RESULTS: Significant variation in neurosurgical care was observed across the region. Kazakhstan showed notable advancements, including an increased number of neurosurgeons and progress in specialized fields such as vascular neurosurgery and brain tumor management. Other countries, like Uzbekistan, Tajikistan, and Kyrgyzstan, made strides in improving neurosurgical care but still faced substantial challenges. Common issues included a shortage of neurosurgeons, limited facilities, and inadequate access to modern technology. The lack of research data further highlighted the need for urgent intervention. CONCLUSIONS: To enhance neurosurgical care in Central Asia, a multipronged approach involving targeted investments, policy reforms, international collaborations, and knowledge sharing is recommended. This includes establishing specialized neurosurgical training programs and fellowships, investing in infrastructure and technology, fostering international collaborations for training and research, introducing early neurosurgery education in medical schools, improving access to online education resources, and promoting telemedicine for consultations and follow-up care. These measures are necessary to expand access to essential neurosurgical care and improve outcomes in the regions.

Endoscopic Therapy of Gastric Varices: Safety and Efficacy of N-Butyl-2-Cyanoacrylate Injection.

Background Upper gastrointestinal bleeding (UGIB) is a common medical emergency that results in significant morbidity, mortality, and socioeconomic burden. Both types of cardio-fundal varices, gastro-esophageal varix 2 (GOV2) and isolated gastric varices type 1 (IGV1), can cause massive bleeding and often are difficult to treat compared to the other types of gastric varices. Endoscopic variceal band ligation (EVBL) is a less effective treatment modality for gastric varices than esophageal varices and is associated with high re-bleeding rates. N-butyl-2-cyanoacrylate (Histoacryl) injection is an effective and potential treatment option for fundal varices. This study aims to evaluate the safety and efficacy of n-butyl-2-cyanoacrylate injection therapy in cardio-fundal varices. Objective To assess the efficacy and safety of n-butyl-2-cyanoacrylate injection therapy for fundal varices. Methods This retrospective observational cohort study was conducted at the Department of Gastroenterology, Allied Teaching Hospital, Gujranwala, over one year. All patients, irrespective of age and gender, presenting with UGIB and in whom fundal varices were diagnosed on gastroscopy followed by n-butyl 2-cyanoacrylate injection therapy were included in this study. The efficacy and safety of Histoacryl therapy were assessed by analyzing successful hemostasis, frequency of re-bleeding, obliteration, and regression of fundal varices on repeat endoscopy. Adverse events such as re-bleeding and mortality related to fundal variceal treatment were documented. Results A total of 60 patients were included in the study. Of these, 70% had IGV1, while the remaining 30% had GOV2. Hemostasis was achieved in 100% of patients following n-butyl-2-cyanoacrylate injection. Successful obliteration with regression of varices was observed in 91.3% of patients. Various adverse events were observed, with abdominal pain being the most common observed complication in 18.3% of participants. However, only 8.3% of participants developed re-bleeding due to ulcer formation at the injection site, and no death occurred directly due to fundal variceal treatment. Conclusion N-butyl-2-cyanoacrylate injection therapy is a lifesaving, effective, and safe intervention for controlling bleeding from cardio-fundal varices, leading to improved health status and a consequent decrease in episodes of recurrent bleeding. Its side effects are few and infrequent. However, larger-scale studies are needed to further evaluate the safety and effectiveness of n-butyl-2-cyanoacrylate injection therapy. These studies will be crucial in establishing comprehensive guidelines for the management of fundal varices.

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol.

BACKGROUND: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. METHODS: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. CONCLUSION: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. STUDY REGISTRATION: This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Association of Metabolic Dysfunction-Associated Steatotic Liver Disease/Non-alcoholic Fatty Liver Disease With Type 2 Diabetes Mellitus: A Case-Control Study in a Tertiary Care Hospital in Pakistan.

Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels, insulin resistance, and relative insulin deficiency. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the term used to describe fatty liver (steatosis) in individuals without a history of significant alcohol intake. MASLD is progressively known as the leading cause of chronic liver disease. Dietary factors, a significant risk factor for developing T2DM and cardiovascular disease, also contribute to MASLD development. The risk of developing MASLD increases with age, particularly in patients with diabetes mellitus. This risk is notably elevated among South Asians due to their higher incidence of insulin resistance and metabolic syndrome. Importantly, MASLD is acknowledged as a component of the metabolic syndrome, with insulin resistance playing a central role in its development. Objective To determine the association between MASLD and T2DM in patients presenting at a tertiary care hospital in Pakistan. Methodology This case-control study was conducted for one year in a tertiary care hospital in Gujranwala, Pakistan. A total of 380 patients were enrolled through convenient sampling and were analyzed according to two groups: those with diabetes (case) and those without diabetes (control). All participants were assessed for serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and underwent abdominal ultrasound to determine hepatic fibrosis. A diagnosis of MASLD was made only in the presence of hepatic steatosis with AST and ALT values of more than 40 IU. The odds ratio (OR) was calculated, and stratified analysis was conducted according to gender, age, and BMI. A p-value of ≤0.05 was considered statistically significant. Results In our study, 55.53% of patients were male, while 44.47% were female. The average BMI (±SD) of the patients was 23.66±3.08 kg/m2. Among the cases group, the MASLD was noted in 91 (47.9%) patients, while among the controls group, the MASLD was noted in 64 (33.7%) patients with a statistically significant OR of 1.810 (1.19-2.74). Conclusion In conclusion, MASLD is significantly associated with T2DM, regardless of gender and BMI of patients. We recommend screening T2DM patients for the presence of MASLD at regular intervals to prevent hazardous consequences of MASLD in adult populations, particularly those with features of metabolic syndrome. Further larger-scale studies investigating the impact of T2DM on MASLD are required to reduce morbidity and decrease disease burden, especially in prevalent areas.

Unsuccessful treatment outcome and associated risk factors. A prospective study of DR-TB patients from a high burden country, Pakistan.

INTRODUCTION: Tuberculosis (TB), a curable and preventable infectious disease, becomes difficult to treat if resistance against most effective and tolerable first line anti-TB drugs is developed. The objective of the present study was to evaluate the treatment outcomes and predictors of poor outcomes among drug-resistant tuberculosis (DR-TB) patients treated at a programmatic management unit of drug resistant tuberculosis (PMDT) unit, Punjab, Pakistan. METHODS: This prospective observational study was conducted at a a PMDT unit in Multan, Punjab, Pakistan. A total of 271 eligible culture positive DR-TB patients enrolled for treatment at the study site between January 2016 and May 2017 were followed till their treatment outcomes were recorded. World Health Organization's (WHO) defined criteria was used for categorizing treatment outcomes. The outcomes of cured and treatment completed were collectively placed as successful outcomes, while death, lost to follow-up (LTFU) and treatment failure were grouped as unsuccessful outcomes. Multivariable binary logistic regression analysis was employed for getting predictors of unsuccessful treatment outcomes. A p-value <0.05 was considered statistically significant. RESULTS: Of the 271 DR-TB patients analysed, nearly half (51.3%) were males. The patient's (Mean ± SD) age was 36.75 ± 15.69 years. A total of 69% patients achieved successful outcomes with 185 (68.2%) patients being cured and 2 (0.7%) completed therapy. Of the remaining 84 patients with unsuccessful outcomes, 48 (17.7%) died, 2 (0.7%) were declared treatment failure, 34 (12.5%) were loss to follow up. After adjusting for confounders, patients' age > 50 years (OR 2.149 (1.005-4.592) with p-value 0.048 and baseline lung cavitation (OR 7.798 (3.82-15.919) with p-value <0.001 were significantly associated with unsuccessful treatment outcomes. CONCLUSIONS: The treatment success rate (69%) in the current study participants was below the target set by WHO (>75%). Paying special attention and timely intervention in patients with high risk of unsuccessful treatment outcomes may help in improving treatment outcomes at the study site.

Caroli's Syndrome: A Case Report and Literature Review.

Synonymous with congenital non-obstructive saccular or fusiform intra-hepatic duct dilatation and congenital communicating cavernous ectasia of the intra-hepatic biliary tract, Caroli's syndrome (CS) is an extremely rare fibro-polycystic liver disorder characterized by ductal plate malformation and consequent peri-portal fibrosis due to segmental intra-hepatic duct dilatation. No more than 200 cases of the syndrome have been reported since 1958. CS may affect one or both lobes of the liver, but more commonly it affects the left hepatic lobe. We describe a rare case of CS localized to the right hepatic lobe in a 21-year-old male, who presented with complaints of upper gastrointestinal (GI) bleeding without any signs or stigmata of chronic liver disease. Personal as well as family history was non-significant except positive for consanguineous parental marriage. General physical examination was unremarkable except for pallor, and upper GI endoscopy revealed columns of bandable esophageal varices which led us to a line of investigations to identify the cause of portal hypertension. Blood tests were non-specific, though imaging studies chiefly abdominal ultrasound, CT abdomen and pelvis with contrast, and magnetic resonance cholangiopancreatography (MRCP) led us to confirmation of the diagnosis of CS in the right hepatic lobe with manifestations of portal hypertension as the predominant feature. Diagnosis was confirmed on liver biopsy which showed right-sided cystic dilations with congenital hepatic fibrosis.

Highly Efficient Perfect Vortex Beams Generation Based on All-Dielectric Metasurface for Ultraviolet Light.

Featuring shorter wavelengths and high photon energy, ultraviolet (UV) light enables many exciting applications including photolithography, sensing, high-resolution imaging, and optical communication. The conventional methods of UV light manipulation through bulky optical components limit their integration in fast-growing on-chip systems. The advent of metasurfaces promised unprecedented control of electromagnetic waves from microwaves to visible spectrums. However, the availability of suitable and lossless dielectric material for the UV domain hindered the realization of highly efficient UV metasurfaces. Here, a bandgap-engineered silicon nitride (Si3N4) material is used as a best-suited candidate for all-dielectric highly efficient UV metasurfaces. To demonstrate the wavefront manipulation capability of the Si3N4 for the UV spectrum, we design and numerically simulate multiple all-dielectric metasurfaces for the perfect vortex beam generation by combing multiple phase profiles into a single device. For different numerical apertures (NA =0.3 and 0.7), it is concluded that the diffracted light from the metasurfaces with different topological charges results in an annular intensity profile with the same ring radius. It is believed that the presented Si3N4 materials and proposed design methodology for PV beam-generating metasurfaces will be applicable in various integrated optical and nanophotonic applications such as information processing, high-resolution spectroscopy, and on-chip optical communication.

Frequency and Management of Adverse Drug Reactions Among Drug-Resistant Tuberculosis Patients: Analysis From a Prospective Study.

Drug-resistant tuberculosis (DR-TB) management is often linked with a higher rate of adverse drug reactions (ADRs) needing effective and timely management of these ADRs, which, if left untreated, may result in a higher rate of loss to follow-up of drug-resistant patients. Study objective: The study was aimed at prospectively identifying the nature, frequency, suspected drugs, and management approaches for ADRs along with risk factors of ADRs occurrence among DR-TB patients at Nishtar Medical University, Hospital, Multan, Pakistan. Materials and Methods: The prospective study included all the DR-TB patients enrolled for treatment from January 2016 to May 2017 at the study site. Patients were evaluated for the treatment-induced ADRs as per standard criteria of the National Tuberculosis Program, Pakistan. Multivariate logistic regression was used to assess the independent variables associated with the occurrence of ADRs. Results: Out of 271 DR-TB patients included in the final analysis, it was observed that 55 patients (20.3%) experienced at least three ADRs. A total of 50 (18.5%) patients experienced zero adverse effects, while 15 (5.5%), 33 (12.2%), and 53 (19.6%) patients experienced one, two, and four ADRs, respectively. Gastrointestinal disturbances (66.7%), nervous system disorders (59.4%), and electrolyte disturbances (55.7%) remained the highest reported ADRs during therapy, followed by arthralgia (49.1%), ototoxicity (24%), pruritic reactions/rash (12.9%), dyspnoea (12.5%), and tinnitus (8.8%). Pulmonary cavitation at the baseline visit (p-value 0.001, OR 3.419; 95% CI (1.694-6.902) was significantly associated with the occurrence of ADRs among DR-TB patients. Conclusion: The frequency of ADRs was high among the study cohort; however, these were managed effectively. Patients with recognized risk factors for ADRs occurrence need continuous clinical management efforts.

Lack of CpG islands in human unitary pseudogenes and its implication.

CpG islands (CGIs) are aggregation of CpG dinucleotides in the promoters of mammalian genes. These CGIs are present in almost all the housekeeping genes and some tissue-specific genes in the mammalian genome. Extensive research has been done on the prevalence and role of CGIs in protein-coding genes. However, little is known about CGIs in pseudogenes. In the current research project, we focused on CGIs in three main classes of pseudogenes e.g., duplicated pseudogenes (DPGs), processed pseudogenes (PPGs), and unitary pseudogenes (UPGs). We discovered a predominant absence of CGIs in the promoters of all three pseudogenes. We also compared the CGI profile of these pseudogenes with their parent genes and found that unitary pseudogenes (UPGs) differ from the DPGs and PPGs in the sense that in the latter, lack of CGIs is a consequential event while in UPGs, this lack of CGIs in their promoters is not a result of pseudogenization process. We also discussed the implication of the results obtained from this comparison. To our knowledge, this is the first-ever study highlighting this aspect of UPGs throwing new insights into the evolution of genome in general and especially in the context of pseudogenes.

A Systematic Review of Transfusion-Transmissible Infections Among Blood Donors and Associated Safety Challenges in Pakistan.

The blood transfusion (BT) system in Pakistan is fragmented, demand-driven and depends on weakly regulated transfusion practices. There is a considerable possibility that transfusion-transmissible infections (TTIs) are contributing to the current epidemic of hepatitis B virus (HBV) and hepatitis C virus (HCV) (affecting 7.4% of the general population) in the country. To study this issue, we conducted a systematic review to identify articles related to TTIs and transfusion safety in Pakistan from January 1, 2010 to January 31, 2020. A review of 33 articles met the final criteria for qualitative synthesis. Analysis of these studies showed a cumulative frequency of HBV 2.04%, HCV 2.44%, HIV 0.038%, syphilis 1.1% and malaria 0.11%. The frequency of coinfections among blood donors varied from 0.0099% to 0.35%. The highest number of coinfections were HCV and syphilis, followed by HCV and HBV infections. Syphilis and malaria were tested in only 38% and 46% of all the blood donations in one study. The rate of voluntary non-remunerated donations (VNRDs) was less than 13%, and male donors were 95% to 100% in these studies. There was a significant difference in the frequency of HBV and HCV in VNRDs (0.48%) as compared to replacement donors (RDs) (4.15%). In short, this review shows a high frequency of TTIs, especially HBV, HCV and syphilis in the blood donor population in Pakistan. There is a high dependency on RDs, minimal use of healthy voluntary blood donation practices, inadequate screening of high-risk donors, repeated collections of the blood from RDs, poor quality of screening methods and limited knowledge of donor health. Without standardized safe transfusion practices, there will be an ongoing increase in transmission of TTIs, especially HBV, HCV, syphilis, and HIV leading to a significant adverse public health impact.

Meningoencefalitis bacteriana. Hospital Pediátrico "José Luis Miranda". Cuba. 2007-2012 / Bacterial meningoencephalitis. Pediatric Hospital "José Luis Miranda". Cuba. 2007-2012

Se realizó un estudio de tipo no experimental, descriptivo, transversal en el Hospital Pediátri-co Universitario "José Luís Miranda", provincia de Villa Clara, Cuba; durante el período 2007 ­ 2012. Se trabajó con la totalidad de la población de estudio, la que estuvo integrado por 56 casos interpretados mediante el método diagnóstico del Síndrome Neurológico Infec-cioso: meningoencefalitis bacteriana, cuyos participantes fueron seleccionados a partir de las Tarjetas de Declaración Obligatoria (EDO). Los datos fueron recopilados mediante la revi-sión de documentos (historias clínicas) y procesados mediante estadísticas descriptivas. El 42,86% de los pacientes correspondió a niños menores de 1 año; así mismo el 21,43% resultó causado por meningococo y una cifra similar por neumococo. Se observó un predominio del género masculino; la etiología fue mayoritariamente neumocóccica y meningocóccica; los síntomas más frecuentes fueron fiebre, cefalea y vómitos escasos; así como la complicación más importante observada resultó el fallecimiento de algunos pacientes.

A non-experimental, descriptive, cross-sectional study was carried out at the "José Luís Miranda" University Pediatric Hospital, in the province of Villa Clara-Cuba, during the period 2007 ­ 2012. The total population of the study was composed of 56 cases interpreted by the diagnostic method of Infectious Neurological Syndrome: bacterial meningoencephali-tis, whose participants were selected from the Obligatory Declaration Cards (ODC). The data was collected by reviewing documents (medical records) and these were processed using descriptive statistics. 42.86% of the patients were children under one year of age; likewise, 21.43% was caused by meningococcus and a similar number by pneumococcus. A predomi-nance of the masculine gender was observed. The etiology was mostly pneumococcal and meningococcal, the most frequent symptoms were fever, headache and poor vomiting; as well as the most important complication observed was the death of some patients.

Caracterización clínico- epidemiológica de la infección por condiloma acuminado. Poli-clínico Universitario "Marta Abreu". Abril 2011-diciembre 2012 / Clinical-epidemiological characterization of infection by condyloma acuminatum. Poli-clínico Universitario "Marta Abreu". April 2011-December 2012

Fue efectuado un estudio descriptivo, longitudinal y prospectivo, en el Policlínico Universi-tario "Marta Abreu ", en la ciudad de Santa Clara, provincia Villa Clara, Cuba, en el período comprendido desde abril del 2011 hasta diciembre del año 2012, con el objetivo de caracteri-zar la relación clínico-epidemiológica en pacientes portadores de la infección por condiloma acuminado. Los pacientes que acudieron a la consulta dermatológica del policlínico, tres mil trescientos cincuenta y cuatro (3 354), representaron el universo y la muestra tomada estuvo integrada por 49 afectados con diagnóstico clínico de condiloma acuminado, la cual estuvo determinada a través del método de muestreo de conveniencia. Se obtuvo la información del cuestionario (Anexo I); aplicado a los pacientes con diagnóstico clínico de condiloma acumi-nado, del Departamento de Estadísticas, las Historias Clínicas Individuales y Entrevistas, revistas científicas y de las fuentes actualizadas del internet. El condiloma acuminado, llama-do por lo general verruga genital o verruga venérea, es considerado como la ITS más frecuen-te y ocupa el segundo lugar en importancia tras el VIH/SIDA. Según el estudio realizado, la infección por condiloma acuminado predominó en las edades entre 20 y 29 años; sexo mas-culino e inicio las relaciones sexuales en edades tempranas a los 15 o 17 años; uso eventual del condón y múltiples parejas sexuales en el año. Predominó el tratamiento tópico a través de la podofilina al 25% y la evolución fue insatisfactoria.

A descriptive, longitudinal and prospective study was carried out at the Policlínico Universi-tario "Marta Abreu", in the city of Santa Clara, province of Villa Clara, Cuba, in the period from April 2011 to December 2012. It aimed to characterize the clinical-epidemiological relationship in patients with condyloma acuminatum infection. Three thousand three hundred fifty four (3 354) patients who were attended in the dermatological consultation represented the universe; the sample taken of 49 affected patients with clinical diagnosis of condyloma acuminatum was determined through the method of convenience sampling. The information was collected from the questionnaire(Annex I) applied to patients with a clinical diagnosis of condyloma acuminatum, from the Department of Statistics, Individual Clinical Stories and Interviews, scientific journals and updated Internet sources. The condyloma acuminatum (usually called genital wart or venereal wart) is considered the most frequent STI and ranks second in importance after HIV / AIDS. Infection by condyloma acuminatum in the ages between 20 and 29 years, male sex, initiation of sexual relations at an early age at 15 or 17 years old, eventual use of the condom, and multiple sexual partners in the year predominated according to the study conducted. Topical treatment with podophyllin at 25% predominated and the evolution was unsatisfactory.

Fighting the Dengue Virus.

The incidence of dengue has been on the upsurge in the last decade. It has affected around one-third of the world's population living in endemic areas. It can be asymptomatic or may present with some specific symptoms. No control measures have proven beneficial to decrease the prevalence of this disease. The emergence of dengue vaccine has been a revolutionary hope in the future of patients affected with this disease. No doubt, this vaccine has its limitations and may do more harm than good, but with correct use, it can prove to be the most beneficial step taken in managing dengue so far.