Comparative efficacy of palliative radiotherapy dose schedules in advanced bladder cancer-associated gross hematuria.

Introduction: Gross hematuria (GH) in advanced/inoperable bladder cancer patients causes significant morbidity. Patients frequently need multiple transfusions. Hypofractionated radiotherapy (RT) has been shown to be effective in symptom palliation. In this study, we explore the efficacy of various fractionation regimens in these patients. Methods: This single institute retrospective analysis was conducted on 60 consecutive patients treated with palliative RT. Fractionation (single versus multiple) and biologically equivalent doses (BED; high ≥36 Gy versus low <36 Gy) were used to compare the efficacy of various fractionation regimens. The primary outcome was the difference in objective response rate (ORR) between various strata at 2, 4, 8 and 12 weeks. Major secondary outcomes were differences in ORR according to Eastern Cooperative Oncology Group (ECOG) performance status (PS) and tumour node metastases (TNM) stage, and the proportion of patients requiring re-transfusion(s) at 12 weeks. Data were analysed using SPSS 23. Results: Overall ORR at 2, 4, 8 and 12 weeks was 86%, 77%, 67% and 55%, respectively. There was no statistically significant difference in response rates between single or multi-fraction, or high versus low BED groups (All p = >0.05). Moreover, ECOG PS (p = 0.11) or TNM stage (p = 0.58) also had no impact on the response rate at 12 weeks. Nearly one-third (31%) of patients required further transfusions at 12 weeks. Conclusion: RT is an effective modality to control GH. No difference in ORR was found between single fractions versus multiple fractions, or high versus low BED regimens. Single fraction RT can be offered to these patients considering low cost, patient convenience and minimal side effects.

Women and Cardiovascular Health: Unraveling Gender-Specific Factors, Risks, and Therapeutic Approaches in Contemporary Medicine.

Background and objective Cardiovascular diseases (CVDs) constitute a significant global health challenge, causing millions of deaths annually and straining healthcare systems worldwide. This study aimed to investigate and elucidate gender-specific factors, risks, and therapeutic approaches related to cardiovascular health in women within the context of contemporary medicine. Methodology We conducted a prospective observational study spanning one year (November 2022 to October 2023) at the Peshawar Medical Complex Hospital, to meticulously explore the field of women's cardiovascular health. With a diverse cohort of 435 women (age range: 18-55 years), representing various socioeconomic backgrounds and geographic locations, our study aimed to elicit comprehensive insights. Through structured interviews covering reproductive history, lifestyle, and psychosocial aspects, coupled with clinical assessments, we gathered multifaceted data. Statistical analysis was done using SPSS Statistics version 23.0 (IBM Corp., Armonk, NY). By employing descriptive and t-tests for quantitative analysis and by thematically analyzing qualitative insights, our approach ultimately sought to provide a nuanced understanding of gender-specific factors impacting women's cardiovascular health. Results The study, involving 435 women, revealed various prevalent cardiovascular risk factors. Notable findings include a high incidence of a family history of CVD (n=213, 48.96%, p=0.013), hypertension (n=207, 47.58%), hypercholesterolemia (n=114, 26.21%), elevated triglycerides (n=162, 37.24%), and diabetes (n=64, 14.71%). Physical inactivity was also significantly more common (53.56%, p=0.004) compared to those engaging in regular activity. Women-specific risk factors comprised miscarriage (n=191, 43.91%). Therapeutic preferences varied, with a majority opting for lifestyle modifications (n=263, 60.39%) and pharmacological interventions (n=331, 76.33%). Conclusions This study provides a comprehensive understanding of prevalent cardiovascular risk factors, distinctive women-specific contributors, and diverse therapeutic preferences, highlighting the importance of personalized and targeted interventions to optimize women's cardiovascular health outcomes in contemporary medicine.

Real-World Challenges of Managing Diffuse Large B-Cell Lymphoma in a Developing Country.

PURPOSE: To highlight challenges and cancer care disparities in patients of diffuse large B-cell lymphoma management in resource-constrained settings. MATERIALS AND METHODS: This multicenter retrospective study included 738 patients from 12 public and private sector hematology-oncology centers across Pakistan. Patients were divided into limited-resource and enhanced-resource settings as per national diffuse large B-cell lymphoma (DLBCL) guidelines. RESULTS: The median age at diagnosis was 47 years (range, 14-89). Male:female ratio was 2.5:1. Majority of the patients (69.3%) were treated in limited-resource settings. Computed tomography was used as a staging modality in 442 (60%) patients. Limited-stage DLBCL was present in 13.5% of patients, while 86.3% had advanced-stage disease at diagnosis. First-line regimens included rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in 56% and cyclophosphamide, doxorubicin, vincristine, prednisone in 34% of patients, while 10% of patients received palliative regimens upfront. Of evaluable data, complete remission was documented in 299 (74.4%) patients, 39 (9.8%) had partial response and 63 (13.5%) had progressive disease. Disease-free survival (DFS) and overall survival (OS) status were not available for 345 (46.8%) patients at the time of data collection. Overall study cohort had a median follow-up of 2.2 years with a median OS of 3.6 years (95% CI, 3.1 to 4.1), median DFS of 3.1 years (95% CI, 2.6 to 3.6), and a 5-year OS of 40% and DFS of 36%. CONCLUSION: Patients from low- and middle-income countries present at an earlier age and have more advanced disease. Patients were frequently lost to follow-up, and record keeping was inadequate more so in patients treated in limited-resource settings. There is a need to establish a national lymphoma registry, improve record keeping, and standardize treatments to ensure improvement in treatment outcomes.

The role of cepharanthine as an anti-atherosclerotic agent in rats.

This investigation assessed the potential of cepharanthine (CEP), a compound from Stephania cepharantha Hayata, in mitigating atherosclerosis in a hyperlipidemic rat model. Using Wistar rats, four distinct diet and drug treatment groups were established: a high-fat high sucrose diet (HFHS), HFHS supplemented with intraperitoneal cepharanthine (HFHS-C) or oral atorvastatin (HFHS-A) from the 8th week, and a normal-fat diet (NFD). The study aimed to evaluate diet and drug impact on aortic histopathological changes over 16 weeks. Our results revealed significant atherosclerosis prevention in the aorta of the HFHS-C group, marked by preserved endothelial integrity, absence of inflammation, and lack of atherosclerotic plaques. Additionally, CEP demonstrated a crucial role in preventing the emergence of cholesterol clefts and foamy macrophages. These findings suggest that CEP effectively curbs atherosclerosis progression in hyperlipidemic rats, reducing arterial fat deposition and offering a potential natural preventative strategy against this disease.

Application of Vessel Navigator™ fusion imaging software in a complex transcatheter palliation of Tetralogy of Fallot with pulmonary atresia.

Extreme pulmonary artery hypoplasia in cyanotic malformations precludes palliative surgeries. When aortopulmonary collaterals (APC) in such patients are also hypoplastic, their unifocalization to create a neopulmonary vasculature is also hampered. Stent angioplasty of the outflow or collateral arteries may reduce hypoxia but is challenging in tortuous and atretic tracts. Fusion imaging overlays anatomical data from computed tomography during adult structural interventions, but its use is not often reported in young children with complex cyanotic malformations. This report shows utility of fusion imaging in pulmonary atresia with extremely hypoplastic pulmonary arteries and stenotic APC to guide stenting of outflow tract and collaterals.

Evaluation of patients for potential compression of anomalous coronaries coursing behind the aortic root before device closure of secundum atrial septal defects.

Coronary arteries coursing behind the aortic root may get compressed when nitinol septal occluders are used to close an atrial septal defect. Hence, echocardiographic recognition of a retroaortic linear vessel is important during preinterventional evaluation. While the left circumflex arising from the right coronary artery is the most common cause, a similar finding is sometimes observed in a single left or right coronary artery and rarely with small sinus nodal branches from the left circumflex artery. Complex three-dimensional relations between the defect and the aortic root may be understood only after a postdeployment selective coronary angiography. Two patients with anomalous retroaortic left circumflex from the right coronary artery underwent uneventful device closure with clearly documented separation between the edges of the occluder and the anomalous vessel. Follow-up imaging and exercise testing confirmed the safety of the intervention. A selective postdeployment and postrelease coronary angiography are mandatory in every patient with retroaortic coronaries.

A Multicenter Study of Clinical Presentations and Outcomes of Multiple Myeloma in Pakistan: The Real-World Analysis in a Resource-Constrained Country.

This is the first multicenter study from Pakistan exploring the prevalence, clinical presentations and treatment outcomes of Multiple Myeloma patients. This retrospective study involved data collection from hospital record system of four tertiary care referral hospitals of Pakistan including all patients diagnosed as having Multiple Myeloma from January 2014 to December 2018. The demographic details, clinical presentations, laboratory findings, treatment responses, and mortalities were evaluated. The progression-free survival and overall survival were analyzed considering relapse and mortality as the end points, respectively. For the progression-free survival, the Kaplan-Meier survival analysis and the log rank test were used to compare the survival function for chemotherapy followed by autologous stem cell transplant (ASCT) as opposed to chemotherapy alone (non-ASCT). The overall survival analysis was assessed by Kaplan-Meier survival analysis. This study identified 403 Multiple Myeloma patients in five years. The median age at presentation was 55 years. Bortezomib based drug regimens were the most commonly used initial treatments (57.5%). Forty three patients received ASCT. The progression-free survival median for ASCT and non-ASCT patients were 50 months (95% CI, 42-57.9 months) and 26 months (95% CI, 21.5-30.5 months), respectively. The cumulative probability of survival rate at 60 months was 80%. This study identified 403 Multiple Myeloma patients over 5 years in four tertiary care hospitals of Pakistan. It underscores the importance of autologous stem cell transplant in Myeloma patients and advocates improving its facilities in Pakistan.

Transcatheter Versus Surgical Closure of Acute Ruptured Sinus of Valsalva Aneurysms with Associated Ventricular Septal Defects.

Transcatheter ruptured sinus of valsalva aneurysm (RSOVA) closure is an alternative to surgery. When a restrictive ventricular septal defect (rVSD) coexists, there are doubts about support for an occluder and persistent left ventricular (LV) dilatation. We compared the outcomes of patients from a single centre with rVSD and RSOVA after surgery or transcatheter intervention in the past 8 years in this study. Location of rVSD did not alter the approach. Compliant balloon interrogation before transcatheter closure was occasionally used to assess significance of interventricular shunt or aortic regurgitation. Procedural success and LV dimensions before and after treatment were analyzed. Seventeen patients with a mean age of 36.64 ± 12.58 years were analyzed. 12/13 catheter procedures (92%) were successful, of whom eight patients had an outlet VSD. rVSD was closed with device in one patient with perimembranous rVSD, but unaddressed in others. Four patients underwent balloon interrogation. Surgery included the single patient who failed intervention. Transcatheter group had more acute symptoms and advanced functional class than surgical group, though not significant. At a median follow-up of 4.5 (1-7.5) years, the mean LV dimensions (50.3 ± 10.1 mm and 50.1 ± 3.1 mm, p = 0.46) were not different in the transcatheter and surgical groups. Mean end-diastolic volumes (110.5 ± 42. 1 ml and 98.5 ± 37.5 ml, p = 0.91) were not significantly different either. Transcatheter RSOVA closure success was not altered by rVSD despite their location underneath the aneurysms, including outlet rVSD with defect in aortoventricular junction. Persistent LV dilatation was not observed after catheter intervention even when the VSD was not closed.

First report of a percutaneous valve-in-Valve implantation of tricuspid valve in a systemic right ventricle.

Severe tricuspid regurgitation in corrected transposition of great arteries is treated with early bioprosthetic replacement to prevent right ventricular failure. When bioprosthesis degenerates, surgery on cardioplegic arrest further complicates right ventricular function. We report the first transcatheter valve-in-valve implantation of tricuspid valve in a systemic right ventricle in corrected transposition describing the modifications due to anatomical differences in these patients.

Acute intraprocedural thrombosis during an arterial ductal stenting successfully managed by eptifibatide.

Acute stent thrombosis may complicate neonatal arterial duct stenting for reduced pulmonary blood flow. Thrombolytic agents recanalise the clot but may cause bleeding around the vascular sheaths and other sites. Since early thrombus is platelet mediated, intravenous platelet glycoprotein inhibitor like eptifibatide is likely to be effective, but rarely utilised in neonates. Ductal stent thrombosis treated with eptifibatide is reported.

Electroosmosis-modulated bio-flow of nanofluid through a rectangular peristaltic pump induced by complex traveling wave with zeta potential and heat source.

Electrokineticmicroperistaltic pumps are important biomechanical devices that help in targeted drugging of sick body parts. This article is focused on mathematical modeling and analysis of some important aspect of such flows in a rectangular duct with wall properties. Effects of zeta potential, heat source, and deby length are also studied. Carbon nanotubes (CNTs) in the Newtonian base fluid are assumed as drugging material. A comparison of single-walled CNTs and multiwalled CNTs is also presented. It is considered that the walls are flexible and encapsulating the region with limited permeability. The defined flow problem is modeled and analyzed analytically for the transport of CNT-water nanofluid. It is accepted that the flow is steady, nonturbulent, and propagating waves do have a considerably longer wavelength when compared to amplitude. The conditions and assumptions lead to a model of coupled partial differential equations of order two. The exact results using the eigenfunction expansion method are procured and shown accordingly. The predictions about the behavior of important parameters are displayed for single-walled CNT and multiwalled CNT-water nanofluidic behavior-using figures. The impact of sundry parametersis are analyzed. The application of the current study involved a transporting/targeted drug delivery system using peristaltic micropumps and magnetic fields in pharmacological engineering.

Mechanistic new insights of flavonols on neurodegenerative diseases.

With a large and increasing elderly population, neurodegenerative diseases such as Parkinson's disease (PD), Huntington disease (HD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS) and Multiple sclerosis (MS) have become a major and growing health problem. During the past few decades, the elderly population has grown 2.5 % every year. Unfortunately, there are no specific therapeutic remedies available to slow the onset or development of these diseases. An aging brain causes many pathophysiological changes and is the major risk factor for most of the neurodegenerative disorders. Polyphenolic compounds such as flavonols have shown therapeutic potential and can contribute to the treatment of these diseases. In this review, evidence for the beneficial neuroprotective effect of multiple flavonols is discussed and their multifactorial cellular pathways for the progressions of age-associated brain changes are identified. Moreover, the animal models of these diseases support the neuroprotective effect and target the potential of flavonols in the treatment of neurodegenerative diseases.

Automatization analysis of the extremely sensitive laser-based dual-mode biomedical sensor.

In order to design and manufacture a reliable biomedical sensor, sensitive tests have to be performed. This is of superlative importance as it has to be used for the general public. Keeping this into account, the test mechanism of such an extremely sensitive sensor is being done that involves exhaustive protocols regarding the checkup and performance of specific parameters. The control system of the setup involves optoelectronic components like fibre Bragg gratings, optical amplifiers and optical couplers that have been mechanized by implementing newly developed algorithms in software (LabView and MATLAB). Performance has been classified by hysteresis curves, scrutiny of timing analysis and investigation of error deviation. This guarantees the credibility and trustworthiness of the said sensor and aids to check out its performance from time to time. This also opens up vistas for further extensions of the project and ongoing applications which has been postulated in the conclusion.

Effects of Radiative Electro-Magnetohydrodynamics Diminishing Internal Energy of Pressure-Driven Flow of Titanium Dioxide-Water Nanofluid due to Entropy Generation.

The internal average energy loss caused by entropy generation for steady mixed convective Poiseuille flow of a nanofluid, suspended with titanium dioxide (TiO2) particles in water, and passed through a wavy channel, was investigated. The models of thermal conductivity and viscosity of titanium dioxide of 21 nm size particles with a volume concentration of temperature ranging from 15 °C to 35 °C were utilized. The characteristics of the working fluid were dependent on electro-magnetohydrodynamics (EMHD) and thermal radiation. The governing equations were first modified by taking long wavelength approximations, which were then solved by a homotopy technique, whereas for numerical computation, the software package BVPh 2.0 was utilized. The results for the leading parameters, such as the electric field, the volume fraction of nanoparticles and radiation parameters for three different temperatures scenarios were examined graphically. The minimum energy loss at the center of the wavy channel due to the increase in the electric field parameter was noted. However, a rise in entropy was observed due to the change in the pressure gradient from low to high.

Modelling Study on Internal Energy Loss Due to Entropy Generation for Non-Darcy Poiseuille Flow of Silver-Water Nanofluid: An Application of Purification.

In this paper, an analytical study of internal energy losses for the non-Darcy Poiseuille flow of silver-water nanofluid due to entropy generation in porous media is investigated. Spherical-shaped silver (Ag) nanosize particles with volume fraction 0.3%, 0.6%, and 0.9% are utilized. Four illustrative models are considered: (i) heat transfer irreversibility (HTI), (ii) fluid friction irreversibility (FFI), (iii) Joule dissipation irreversibility (JDI), and (iv) non-Darcy porous media irreversibility (NDI). The governing equations of continuity, momentum, energy, and entropy generation are simplified by taking long wavelength approximations on the channel walls. The results represent highly nonlinear coupled ordinary differential equations that are solved analytically with the help of the homotopy analysis method. It is shown that for minimum and maximum averaged entropy generation, 0.3% by vol and 0.9% by vol of nanoparticles, respectively, are observed. Also, a rise in entropy is evident due to an increase in pressure gradient. The current analysis provides an adequate theoretical estimate for low-cost purification of drinking water by silver nanoparticles in an industrial process.

Ways to manage hepatitis C without cirrhosis: Treatment by comparison of coded eastern medicine hepcinal with interferon alpha 2b and ribavirin.

Hepatitis C virus (HCV) infection is a serious and significant global health problem in the Pakistan and elsewhere. In majority of cases HCV infection remains asymptomatic but in advance cases it may progress to fibrosis of liver, shrinkage of liver cells or failure of liver. The hepatitis C may progress to cause liver cirrhosis that mostly develop in 20% of the affected patients in 20 years with an increased risk in male, alcoholic drink, immune-compromised and who acquire HCV infection after the age of 40 years. This was an open-label prospective study conducted on 66 clinically and immunologically diagnosed cases of HCV infection. In Hepcinal treated group, there were significant improvement in HCV associated symptoms compared to control group (p<0.05). While Interferon therapy resulted in significant improvement in serological response (55.88%) compared to Hepcinal treated patients (46.88%). It was concluded that Hepcinal has shown better clinical response but no significant serological response (p=0.3244) and it might be an alternative therapy to treat hepatitis C infection and to prevent its progression into chronic ailment.

Clinical efficacy of polyherbal formulation Eezpain spray for muscular pain relief.

The topical herbal formulation Eezpain spray consisting of natural ingredients that have been clinically proved for its analgesic and anti-inflammatory activity. The designed formulation on application knee and wrist joints, back of neck and shoulder, forearms and lower back exhibited significant efficacy. A total of 20 subjects both male and female applied Eezpain spray consisting of Gaultheria oil, Eucalyptus oil, Turpentine oil, Clove Oil, Menthol and Camphor. All the active materials are cited that these have analgesic activity in myalgia and neuralgia. The study design was prospective and opens as pilot study followed the inclusion and exclusion criteria. All the sign and symptoms were noted at baseline and at the end of 14 days treatment performance was evaluated. The statistical analysis was done by using Microsoft Excel2007 and SPSS version 18.0. It is concluded that Eezpain spray has shown efficacy in mild to moderate cases on applying locally to the affected parts to relieve pain from different ailments.

A novel HPTLC method for quantitative estimation of biomarkers in polyherbal formulation

Objective: To explore the quantitative estimation of biomarkers gallic acid and berberine in polyherbal formulation Entoban syrup. Methods: High performance thin layer chromatography was performed to evaluate the presence of gallic acid and berberine employing toluene: ethyl acetate: formic acid: methanol 12:9:4:0.5 (v/v/v/v) and ethanol: water: formic acid 90:9:1 (v/v/v), as a mobile phase respectively. Results: The R

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. Due to the rapid advancements in the knowledge and available information, a consortium of members from countries across Asia Pacific, "APASL ACLF Research Consortium (AARC)," was formed in 2012. A large cohort of retrospective and prospective data of ACLF patients was collated and followed up in this data base. The current ACLF definition was reassessed based on the new AARC data base. These initiatives were concluded on a 2-day meeting in February 2014 at New Delhi and led to the development of the final AARC consensus. Only those statements which were based on the evidence and were unanimously recommended were accepted. These statements were circulated again to all the experts and subsequently presented at the annual conference of the APASL at Brisbane, on March 14, 2014. The suggestions from the delegates were analyzed by the expert panel, and the modifications in the consensus were made. The final consensus and guidelines document was prepared. After detailed deliberations and data analysis, the original proposed definition was found to withstand the test of time and identify a homogenous group of patients presenting with liver failure. Based on the AARC data, liver failure grading, and its impact on the "Golden therapeutic Window," extra-hepatic organ failure and development of sepsis were analyzed. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals, and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information are presented here.

Aortic dilatation with bicuspid aortic valves: cusp fusion correlates to matrix metalloproteinases and inhibitors.

BACKGROUND: Congenital bicuspid aortic valves (BAVs) result from fusion of 2 valve cusps, resulting in left-noncoronary (L-N), right-left (R-L), and right-noncoronary (R-N) morphologic presentations. BAVs predispose to ascending thoracic aortic aneurysms (ATAAs). This study hypothesized that ATAAs with each BAV morphologic group possess unique signatures of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of metalloproteinases (TIMPs). METHODS: Ascending thoracic aortic aneurysm tissue from 46 patients with BAVs was examined for MMP/TIMP abundance, and global MMP activity was compared with normal aortic specimens (n=15). Proteolytic balance was calculated as the ratio of MMP abundance to a composite TIMP score. Results were stratified by valve morphologic group (L-N [n=6], R-L [n=31], and R-N [n=9]). RESULTS: The BAV specimens (p<0.05 versus normal aorta, 100%) displayed elevated global MMP activity (273%±63%), MMP-9 (263%±47%), and decreased MMP-7 (56%±10%), MMP-8 (58%±11%), TIMP-1 (63%±7%), and TIMP-4 (38%±3%). The R-L group showed increased global MMP activity (286%±89%) and MMP-9 (267%±55%) with reduced MMP-7 (45%±7%), MMP-8 (68%±15%), TIMP-1 (58%±7%), and TIMP-4 (35%±3%). The L-N group showed elevated global MMP activity (284%±71%) and decreased MMP-8 (37%±17%) and TIMP-4 (48%±14) activity. In the R-N group, MMP-7 (46%±13%) and MMP-8 (36%±17%) and TIMP-1 (59%±10%) and TIMP-4 (42%±5%) were decreased. The R-L group demonstrated an increased proteolytic balance for MMP-1, MMP-9, and MMP-12 relative to L-N and R-N. CONCLUSIONS: Each BAV morphologic group possesses a unique signature of MMPs and TIMPs. MMP/TIMP score ratios suggest that the R-L group may be more aggressive, justifying earlier surgical intervention.